The Laboratory Swine

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com
preface
Laboratory swine is a relatively unknown species, although the
use of swine in research dates back centuries. However, the
number of swine used in research stands no comparison with
the number of rodents used. Recently, the pattern of animal
use has changed because of a move toward replacement, reduc-
tion, and refinement in animal experimentation. This has caused
an increase in the number of swine, because swine, and min-
iature swine in particular, are seen as an alternative to other
nonrodent species such as dogs and primates.
This book in the Laboratory Animal Pocket Reference Series
was written to provide a source of information on laboratory
swine. It is aimed at animal caretakers, technicians, and inves-
tigators, but the laboratory animal veterinarian may also want
to use this book as a reference. This book provides an overview,
not an in-depth review of the use of swine. Extensive references
are given for further study.
It is our hope that this book will contribute to the humane
use of laboratory swine with the housing, husbandry, veterinary
care, and experimental techniques that are appropriate to the
species-specific physiology and behavior of swine.
1999 CRC Press LLC

the authors
Peter Bollen, B.Sc., M.Sc., has studied veterinary medicine
at the University of Utrecht, the Netherlands, turning to labo-
ratory animal science during the preclinical part of this study.
He graduated as an experimental zoologist, after which he con-
tinued his studies of laboratory animal science at the Royal
Veterinary College in London, England, obtaining his M.Sc.
degree in 1994. He joined Ellegaard Gttingen Minipigs, a lab-
oratory swine breeding station, where he is currently the scien-
tific manager. In 1998, he began a research project determining
the nutritional requirements of miniature swine, leading to a
Ph.D. thesis. The work is supported by the Danish Academy of
Technical Sciences, and is being carried out at the Biomedical
Laboratory of the University of Southern Denmark in Odense,
Denmark.
Axel Kornerup Hansen, Dr.Vet.Sci., DVM, is professor of

Laboratory Animal Science and Welfare at the Royal Veterinary
and Agricultural University in Copenhagen, Denmark, from
which he also graduated in veterinary medicine in 1985. After
a period in small animal practice and a laboratory animal breed-
ing center, he was appointed assistant director at the Depart-
ment of Experimental Medicine at the University of Copenhagen,
where he was in charge of the health monitoring laboratory. In
1996 he earned his doctorate with a thesis about health mon-
itoring and microbiological quality of laboratory rats. In his
present position, Dr. Hansen's main research interest is in lab-
oratory animal infections, as well as methods for improving the
welfare of animals used for research. Dr. Hansen has published
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more than 100 scientific papers and chapters in textbooks, and
has been involved in setting up European guidelines for health
monitoring of a range of animal species.
Helle Juul Rasmussen, DVM, is appointed as a veterinary

surgeon at the Biomedical Laboratory of the University of South-
ern Denmark in Odense, Denmark. She graduated in veterinary
medicine from the Royal Veterinary and Agricultural University
in Copenhagen, Denmark, in 1991, and worked in veterinary
practice from 1991 to 1996. Since 1997 she has worked in the
field of laboratory animal science, and was appointed to the
Department of Experimental Medicine at the University of
Copenhagen, Denmark. In 1998 she joined the Biomedical Lab-
oratory of the University of Southern Denmark in Odense, Den-
mark. She is currently involved in research and teaching
programs dealing with surgery and microsurgery, anesthesia,
and pain relief of laboratory animals.
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contents
1 IMPORTANT BIOLOGICAL FEATURES
Breeds
The Landrace
The Yorkshire or Large White
The Duroc
The Hampshire
The Pitrain
Other Breeds
Hybrid Breeds
Miniature Breeds
The Vietnamese Potbelly Pig
Nomenclature
Behavior
Anatomical and Physiological Features
Integument and Skeleton
Digestive System
Abdominal Organs
Cardiovascular System
Pulmonary System
Lymphatic and Endocrine System
Normative Values
2 HUSBANDRY
Housing
Environmental Conditions
Temperature and Humidity
Ventilation
Illuminaton
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Noise
Environmental Enrichment
Group Housing
Individual Housing
Nutrition
Nutrient Requirements
Feeding Levels
Sanitation
Frequency
Methods
Transportation
Record Keeping
3 MANAGEMENT AND QUALITY ASSURANCE

Microbiological Management and Quality
Impact of Infections on Animal Research using Swine
Zoonotic Diseases
Legal Regulations
Precautions to Prevent Infections
Common Findings in Health Monitoring
Genetic Monitoring
Accreditation
AAALAC
ISO 9000
Other Organizations
4 VETERINARY CARE
Clinical Examination of Swine
Microbiological Sampling
Diseases of Swine
Therapeutic Treatment
Pathological Examination
Anesthesia and Analgesia
Reactions of Swine to Sedation and Anesthesia
Routes of Administration of Sedatives and Anesthetics
Preanesthetic Management
Premedication
Anesthetic Induction
Endotracheal Intubation
General Anesthesia
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Anesthetic Maintenance and Assessment of Anesthetic
Depth
Drugs used in Swine Anesthesia
Analgesia
Pain Control
Pain Recognition in Swine
Drugs used in Swine Analgesia
Monitoring during Anesthesia
Anesthetic Support
Anesthetic Emergencies
Malignant Hyperthermia/Porcine Stress Syndrome
Postoperative Management
Euthanasia
5 EXPERIMENTAL TECHNIQUES
Restraint
Sampling Techniques
Blood Sampling
Urine and Feces
Cerebrospinal Fluid
Bile and Pancreatic Excretions
Administration of Compounds
Basic Surgical Procedures
Catheterization
Catheter Maintenance
Laparotomy
Safety Testing of Chemicals and Drugs
Necropsy
6 RESOURCES
Associations
Books
Journals
Internet Resources
Swine Diet and Equipment
BIBLIOGRAPHY
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1
important biological
features
Swine are increasingly used as models in biomedical research.

Developments in the field of immunology and xenotransplanta-
tion prospects have renewed interest in this species, the anat-
omy and physiology of which have notable similarities to those
of man. Since their development at the beginning of the 1950s,
miniature swine have been used in toxicity testing as a nonro-
dent species. The small size of miniature swine is obviously
advantageous for housing and handling, but also for the quan-
tity of test compound, which usually is available in only small
amounts. Moreover, pressure from society to reduce the number
of monkeys and dogs in biomedical research has caused an
increase in the use of (miniature) swine.
breeds
The wild boar, Sus scrofa, is the ancestor of all modern breeds
of swine. First evidence of domestication in Europe is some 3500
years old, although the cradle of the domesticated swine is
claimed to have been in China, about 10,000 years ago1. The
American continent has no indigenous wild swine, except the
distantly related Tayassuidae (peccaries). Sus scrofa is a member
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TABLE 1.1: CLASSIFICATION OF SUIFORMES.
Order Suborder Family Genus Species
Artiodactyla Suiformes Hippopotamidea Hippopotamus

amphibius
(hippopothamus)
Hexaprotodon
liberiensis
(pygmy
hippopotamus)
Tayassuidae Pecari tajacu
(collared peccary)
Tayassu pecari
(white-lipped
peccary)
Catagonus
wagneri
(Chacoan peccary)
Suidae Babyrousa Babyrousa
babyrussa
(babirusa)
Phacochoerus Phacochoerus
africanus
(common warthog)
Phacochoerus
aethiopicus
(Somali warthog)
Potamochoerus Potamochoerus
porcus
(red river hog)
Potamochoerus
larvatus
(bushpig)
Hylochoerus Hylochoerus
meinertzhageni
(giant forest hog)
Sus Sus scrofa
(Eurasian wild boar)
Sus salvanius
(pygmy hog)
Sus verrucosus
(Javan warty pig)
Sus barbatus
(bearded pig)
Sus celebensis
(Sulawesi warty pig)
Sus phillippensis
(Philippine warty
pig)
Sus cebifrons
(Visayan warty pig)
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of the swine family (Suidae), which includes species of non-
ruminant, even-toed ungulates. Suidae are omnivores, and are
divided into five genera, with a total of 13 species.
Through selection, numerous breeds of swine have been
developed. Existing breeds are relatively young in comparison
to the history of domestication of swine. Local Celtic swine with
lop ears were widespread in European countries in the 18th and
19th centuries, and are considered to be the primogenitors of
the Landrace. Crosses with Chinese breeds in the early 1800s,
Fig. 1.1 Landrace (Photo Leif Schack-Nielsen/Biofoto)
and with English breeds in the late 1800s, established the

Danish Landrace, which was widely used for the derivation of
other national Landrace breeds. The Yorkshire or Large White,
a breed with pointed, standing ears, originated in England and
was exported to many countries around the world during the
last half of the 19th century. The breed association for the
American Yorkshire was established in 1893. Swine are numer-
ous worldwide. In 1997, annual swine production counted 56
million in the United States. The total figure for the 15 countries
of the European Union was 119 million, with Denmark, the
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Netherlands, France, Spain, and Germany as the leading swine
producing countries. These figures have not changed much
during the last five years.2
A short description of common breeds follows, based on
descriptions from Porter (1993)1 and Jones (1998)3, whereas the
average weights are from Sambraus (1992).4
The Landrace
The Landrace swine has a white-colored, long body and lop ears.
It has a long head, with a slightly concave nose line. The Lan-
drace breed is extremely variable in type and has its own distinct
characteristics in different countries. The average weight of sows
is 273 kg (601 lbs), and boars weigh 312 kg (687 lbs).
The Yorkshire or Large White

The Yorkshire or Large White is a large, white breed of medium
length. It has pointed, standing ears and a concave nose line.
The sow is very fertile, with a litter size of 11, and weighs an
average of 280 kg (617 lbs). The average weight of boars is 320
kg (705 lbs).
Fig. 1.2 Yorkshire (Photo Leif Schack-Nielsen/Biofoto)
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Fig. 1.3 Duroc (Photo Leif Schack-Nielsen/Biofoto)
The Duroc
The Duroc is a red swine with a large frame and semilop ears.
The color varies from light to deep red. The Duroc is good-
natured. The average weight of sows is 300 kg (661 lbs), and
boars weigh 350 kg (771 lbs).
The Hampshire
The Hampshire is black with a white belt over the shoulder. Its
body is compact and the legs relatively short. Its ears are pointed
and standing, and its nose line is concave. The average weight
of sows is 280 kg (617 lbs), and boars weigh 320 kg (705 lbs).
The Pitrain
The Pitrain is a short breed with a broad, deep body. Its color
is white with gray or black patches. It has short, pointed, stand-
ing ears. This breed is mainly used to improve meat quality in
hybrid breeds. The Pitrain is very susceptible to stress. The
average weight of sows is 266 kg (586 lbs), and boars weigh 277
kg (610 lbs).
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Fig. 1.4 Hampshire (Photo Leif Schack-Nielsen/Biofoto)
Other Breeds
In 1990, the National Association of Swine Records had regis-
tered only eight pure-bred swine. Besides the Landrace, York-
shire, Hampshire, and Duroc, the Berkshire, Chester White,
Poland China, and Spotted were registered.1
Hybrid Breeds
Purebred swine are found almost exclusively in breeding herds.
Modern production herds, however, utilize cross-breeding to
produce hybrid grower swine. Hybrid breeds currently dominate
the market; consequently, swine procured for the laboratory
from an agricultural producer will most likely be of mixed breed.
Triple-crossed, such as Yorkshire x Landrace (YL) sows with a
Duroc (D) boar, are common.
Miniature Breeds
Miniature swine are especially bred for research purposes. Many
of the present breeds of miniature swine have their origin in the
Minnesota (Hormel) minipig, which was bred from 1949 at the
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Fig. 1.5 Gttingen minipig
Fig. 1.6 Yucatan micropig (Photo courtesy of Charles River

Laboratories)
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Fig. 1.7 Sinclair minipig (Photo courtesy of Sinclair Research
Center)
Fig. 1.8 Hanford minipig (Photo courtesy of Charles River Lab-

oratories)
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Hormel Institute in Austin, Texas. Miniature swine derived from
this population are the Gttingen minipig (1961) and the Sinclair
minipig (1965). Other breeds are the closely related Hanford
(1958) and Pitman-Moore (1969) miniature swine. A Mexican
feral swine was introduced into the laboratory in 1960 and later
referred to as the Yucatan minipig. From 1972, a smaller subline
of the Yucatan was selected, the Yucatan micropig. Several other
breeds have been established, including the Ohmini and Clawn
minipig in Japan.
There are two weight categories of minipigs: a 35-55 kg (77-
121 lbs) and a 70-90 kg (154-198 lbs) adult weight category. To
the first category belong the Gttingen minipig and the Yucatan
micropig, whereas the Hanford and Yucatan minipigs belong to
the latter category.
The Vietnamese Potbellied Pig

This is a small Asian black breed with wrinkled skin, especially
on the face. Its ears are short and standing, and its abdomen
is round, almost touching the ground. The Vietnamese potbellied
pig is not well suited for the laboratory because of its vigorous
character.
Nomenclature
Since many different breeds of swine exist, each bred and
selected for prevailing characteristics, it is essential to report in
scientific publications which breed was used for a study in order
to facilitate a true comparison of experimental results among
laboratories. In commercial breeding, breeds generally are
referred to with capitals, but this may not be desirable for the
scientific community because of unfamiliarity with this system.
A nomenclature system, as the one used for rodents, is not
known for laboratory swine. Until international rules for swine
nomenclature have been established, the scientifically correct
way of presenting data includes breed, gender, age, and weight,
besides supplier and housing conditions.5
The definitions of common terms used for swine, are given
below:
Swine, hog, or pig Denotation for the species Sus
scrofa; the first two terms are
commonly used in American
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literature, whereas the latter is
mainly used in British literature.
Sow Sexually mature female
Gilt Sexually immature female
Boar Sexually mature male
Barrow Castrated male
Piglet Juvenile swine
Porcine Adjective used in relation to
swine
behavior
An important reason why swine became the subject of domes-
tication is their behavior. Their feeding, sexual and social behav-
ior, and typically docile nature and general adaptability, favored
domestication. Compared to wild swine, domesticated swine are
calmer, quieter, and less active, although they still share many
behavioral characteristics with wild swine, such as social feeding
and explorative behavior.6
Wild swine live in small social groups formed by sows and
their offspring. Young males live in bachelor groups, whereas
adult boars tend to be solitary. In groups of females a social
dominance order is quickly established. Generally, the level of
aggression, mainly expressed by butting or biting the neck and
ears, quickly subsides in stable social groups. Sexually mature
males may fight fiercely, especially in the presence of females.
Newborn swine establish a social order, the teat order, within
a few days after birth. As soon as a teat order has been estab-
lished, each piglet consistently suckles the same teat. Dominant
piglets generally occupy the more productive anterior teats. If
young swine from different litters are mixed after weaning, a
new dominance hierarchy will be established. Ranking is the
result of aggressive interaction, but may take place without overt
aggression. It exists as long as a group is together. Subordinates
which have been separated from a group will be attacked after
reintroduction, whereas a dominant animal may be separated
and reintroduced without any trouble.7
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Wild swine spend most of the day rooting and collecting food.
Their feeding and explorative behavior are closely linked. During
a day, swine eat many small portions. Swine are omnivorous
and diurnal, with elevated activity during the evening. In the
laboratory, activity of swine is related to the presence and activ-
ity of humans, rather than the light-dark cycle.8
anatomical and physiological features9, 10, 11, 12

Integument and Skeleton
The skin of swine has anatomical and physical similarities with
human skin; consequently, swine are often used as models for
percutaneous absorption, skin toxicology, and wound-healing
studies.
Swine have short, sturdy bones. The number of ribs varies
greatly, from 13 to 17, but most commonly 14 or 15 ribs are
present. The bony structure of the thorax is considerably smaller
than the external dimensions suggest. The skull is extremely
sturdy and has a largely extended frontal sinus. Swine are used
in osteoporosis research and cartilage-repair studies.
Digestive System
Swine have an extensive dentition, with 44 elements. For this
reason they are often used in dental research. The formula for
the permanent teeth is i3/3, c1/1, p4/4, m3/3. The canine
teeth or tusks can be found in both boars and sows, but are
most developed in boars. The boars tusks grow throughout the
animal's life. Swine are born with 8 teeth, the needle teeth (i1/1,
c1/1). After two months, two more deciduous incisors and three
of the deciduous premolars have erupted (i3/3, c1/1, p3/3). At
6 months, the first permanent teeth erupt. The swine is at least
18 months old before all permanent teeth have erupted.
Swine are monogastric, and the stomach has a large fundus
and a diventriculum. The area where the esophagus enters the
stomach has nonglandular mucosa and is prone to peptic ulcers.
The bile duct and pancreatic duct enter the duodenum. Similar
to man, swine have an unbranched pancreatic duct, which
makes swine good models for studying pancreatic secretion. The
jejunum and ileum contain numerous patches of lymph nodes.
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TABLE 1.2: BASIC BIOLOGICAL PARAMETERS (RANGE) OF SWINE, AND
MINIATURE SWINE WITH ADULT WEIGHTS OF 35-55 KG AND 70-90 KG.
Parameter Swine Miniature swine

35-55 kga 70-90 kgb
lifespan (yrs) 10-15 10-15 10-15

body temperature 38-39 37-38 38-39
(oC)
chromosomes (2n)14 38 38 38
weight at birth (kg) 1.3-1.9 0.4-0.7 0.6-1.0
weight at 6 mths 90-110 12-22 25-40
(kg)
weight at 1 yr (kg) 150-180 25-40 45-70
weight at 2 yrs (kg) 200-300 35-55 70-90
energy intakec 49-56 13.8-20.2 21.9-29.2
(MJ/day)15
food intakec,d 3.6-4.1 1.0-1.5 1.6-2.1
(kg/day)
water intake 80-120 80-120 80-120
(ml/kg/day)16
a) Yucatan micropig, Gttingen and Sinclair minipig

b) Yucatan and Hanford minipig
c) voluntary intake (ad libitum); metabolizable energy (ME) = 1.2 x W0.75 (MJ/day),
calculated for the body weight (W) at 6 months of age
d) voluntary intake (ad libitum); energy concentration (ME) = 13.6 MJ/kg (3265
kcal/kg)
The large intestines are coiled and voluminous. Because of the

structure and large volume, the cecum lies to the left.
Abdominal Organs
The liver has much fibrous tissue, giving the surface a net-like
appearance. The pancreas has two lobes, which are difficult to
identify. The kidneys have multiple papillae protruding into a
central renal pelvis via the calyces. In structure and size they
are similar to human kidneys. Lymph nodes are located along
all major arteries in the abdomen. The uterine horns in sows
are very long, and the cervix is tightly closed with mucosal
ridges. The boar has large testes and various accessory genital
glands. The ejaculate is voluminous, 200-500 ml. The penis is
fibrous and has a corkscrewed tip. The preputial diverticulum
produces a strong odor.
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TABLE 1.3: HEMATOLOGICAL PARAMETERS (RANGE) OF SWINE, AND
Parameter Swine17 18 Miniature swine
35-55 kga 19 20 70-90 kgb 21
RBC (106/mL) 4.4-8.6 5.30-9.25 5.6-8.8

Hemoglobin (g/dL) 9.0-16.2 9.0-15.8 13.1-17.0
Hematocrit (%) 33.9-45.9 32-61 36.3-53.7
MCV (fL) 17.6-79.6 40.0-73.0 58.2-72.5
MCH (pg) 15.2-56.3 15.2-26.4 18.9-24.3
MCHC (%) 29.4-35.9 29.4-37.9 31.1-34.5
WBC (103/mL) 6.3-21.1 4.4-26.4 6.9-21.2
Segmented 22.0-60.6 10.0-80.0 18.0-94.0
neutrophils (%)
Band neutrophils (%) 0-4.2 0-4.0 0-2.0
Lymphocytes (%) 38.1-73.1 14.0-87.0 21.0-71.0
Monocytes (%) 0-15 0-13.0 2.0-15.0
Eosinophils (%) 0-7.7 0-8.0 0-13.0
Basophils (%) 0-1.3 0-3.0 0-5.0
Platelets (103/ml) 220-665 148-898 217-770

Cardiovascular System
The heart of the swine is small in relation to body size. The
coronary distribution is similar to that of humans, but the left
azygous vein ends directly in the heart instead of in the caval
vein. Swine develop atherosclerosis of the major arteries after
ingestion of a lipidous diet over a relatively short period.
Pulmonary System
Swine have a tracheal bronchus to ventilate the right cranial
lobe; consequently, endotracheal intubation should not continue
as far as the tracheal bifurcation.
Lymphatic and Endocrine System

The lymph nodes of swine are inverted, with the follicular centers
in the medulla. The parathyroids are not located near the thy-
roids, but are related to the thymus. The right adrenal lies in
close contact with the caudal caval vein, which disables total
adrenalectomy.
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Normative Values
Biological, hematological, clinical chemical, and respiratory and
cardiovascular parameters are presented in Tables 1.2-1.6.
When comparing data, it is important to compare data from age-
matched, rather that weight-matched swine.13 However, varia-
tion between individuals and breeds may occur due to genotype,
environment, and experimental procedures.
TABLE 1.4: CLINICAL CHEMICAL PARAMETERS (RANGE) OF SWINE, AND

Parameter Swine 22 Miniature swine

35-55 kga 19 20 70-90 kgb 21 23
Glucose (mg/dL) 48-135 43-133 56-153

Creatinine (mg/dL) 1.2-2.0 0.5-1.6 1.2-2.0
Bilirubin (mg/dL) 0.0-0.3 0.0-0.2 0.0-0.3
Cholesterol (mg/dL) 50-140 39-131 47-173
Total protein (g/dL) 2.25-8.15 6.0-8.8 6.3-9.4
Albumin (g/dL) 0.5-4.3 2.9-3.8 4.1-5.6
Globulin (g/dL) 1.4-3.6 1.5-5.2 1.4-3.6
A:G ratio 1.1-3.5 0.9-1.7 1.1-3.5
Sodium (meq/L) 133-153 132-146 142-153
Potassium (meq/L) 3.1-6.2 3.5-7.4 3.9-5.2
Chloride (meq/L) 96-117 94-140 95-114
Calcium (mg/dL) 5.5-15.7 8.6-12.6 9.3-11.6
Phosphorus (mg/dL) 4.8-9.8 4.9-9.8 5.0-8.3
AST (IU/L) 14-56 13-47 15-53
ALT (IU/L) 5-78 40-106 20-48
CK (IU/L) 52-326 105-6000 37-270
GGT (IU/L) 14-34 25-78 41-86
LDH (IU/L) 140-1155 462-1800 389-727

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TABLE 1.5: RESPIRATORY AND CARDIOVASCULAR FUNCTION (MEAN + SD)
OF CONSCIOUS SWINE, AND MINIATURE SWINE WITH ADULT WEIGHTS OF
35-55 KG AND 70-90 KG.

35-55 kga 25 70-90 kgb 13 26
heart rate 105 10.6 83 15 105 7

mean arterial blood 102 9.3 97 14 89 3
pressure (mmHg)
respiration rate 20 2.9 20 9 25 4
arterial pH 7.48 0.03 7.43 0.03 7.48 0.04
arterial pCO2 (mmHg) 40 2.3 40 3 43 4
arterial pO2 (mmHg) 71 3 109 17 84 4

TABLE 1.6: REPRODUCTION PARAMETERS OF SWINE, AND MINIATURE SWINE

WITH ADULT WEIGHTS OF 35-55 KG AND 70-90 KG.

35-55 kga 27 28 70-90 kgb 29
sexual maturity 6 4-5 6

(months)
minimum breeding age 7 5-6 7
(months)
estrus cycle (days) 14 14 14
length of estrus (days) 3 3 3
length of pregnancy 114 114 114
(days)
litter size 10-14 5-8 5-8
weight at birth (kg) 1.30 0.45-0.60 0.60-1.00
age at weaning (days) 28-35 28-35 28-35

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1035/ch02 Page 17 Tuesday, November 9, 1999 1:37 PM
2
husbandry
An important factor for the successful use of swine in biomedical

research is knowledge about the specific husbandry require-
ments of swine. Housing, feeding, and care should be appropri-
ate to the anatomy, physiology, and behavioral characteristics
of this species. Changes in environmental conditions, feeding,
and care may have an impact on experimental results in swine
30
studies.
housing
At a typical commercial breeding establishment, separate quar-

ters are provided for:
Young stock from weaning to breeding age (growing quar-
ters)
Dry sows and gilts, and breeding boars (mating quarters)
Pregnant sows (waiting quarters)
Parturient and nursing sows (farrowing quarters)
In the growing quarters, swine are housed in groups of the

same sex. Groups will live in good harmony when enough space
per animal is available. They can move around freely to avoid
aggressive interaction. Large groups or groups in a confined
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Fig. 2.1 Group pen at a breeding facility with solid concrete

floor in the back, and grids in the front. The minipigs are fed
from the floor, and chains are hanging from the sides for envi-
ronmental enrichment.
space are not able to maintain a stable dominance order, result-

31
ing in a higher level of aggression. Stable social groups are
best established after weaning.
Young gilts and pregnant sows are group housed. In the
farrowing quarters, sows are caged in special farrowing crates
equipped with bars, preventing them from lying on their young.
7
Breeding boars are housed individually.
Pigs kept at the laboratory can be housed individually or in
small groups in floor pens. The floor can be made of solid
concrete or raised grids. Concrete floors should have a rough
surface for secure footing, and may be coated with an epoxy
layer. Bedding should be provided, e.g., wood shavings or straw.
This gives good rooting and nesting possibilities for the animals,
but is more laborious during sanitation. Grid floors provide good
sanitation since usually no bedding is provided. Grid floors can
be made of galvanized steel, plastic-coated steel, or fiberglass,
and may consist of parallel bars or have a mesh structure.
Galvanized steel is less suitable since it conducts heat too well,
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Fig. 2.2 Single pen at a research facility with solid concrete

floor in the back, and grids in the front. The floor is covered
with wood shavings, and the minipigs are offered hay for envi-
ronmental enrichment (Photo courtesy of Scantox).
whereas plastic-coated steel and fiberglass preserve heat more

satisfactorily. However, when using raised grid floors room tem-
perature is more critical, as compared to concrete floors with
bedding since the animals have no possibility of nesting and
creating an insulated microenvironment. Attention should be
paid to the spacing of the grids so that hooves will not be
damaged. When using parallel bars, a bar width of approxi-
mately 10 mm and a spacing of approximately 12 mm is appro-
priate for most sizes of swine. Plastic-coated, diamond-shaped
grids (Tenderfoot) with a spacing of 10-15 mm is a very satis-
factory floor type for swine. When swine are housed on grid
floors, hooves need to be trimmed at regular intervals since they
do not wear down on grid floors as they do on concrete floors.
Pens should be robust, since swine are forceful animals with
strong snouts. They also rub their sides along the sides of the
pen, pushing with considerable weight. Concrete or brick walls
are most often used in combination with a fencing of galvanized
1999 CRC Press LLC

or stainless steel. No sharp edges or protruding bolts should be

present. Especially when animals are single housed, fencing
should be placed in such a way as to make it possible for the
animals to see, smell, and hear each other. Swine are social
animals and need to have visual, olfactorial, and auditory con-
tact if physical contact is not possible.
Young swine and miniature swine can be housed in dog
facilities without major adaptions to the pens. Usually, only
lowering automated watering valves and feeding bowls is nec-
essary. Automated watering valves are preferred to water bowls
since swine drink considerable amounts of water during a day,
and water should be constantly available. Feeding bowls should
be secured to the cage, and should be made of a smooth material
that is easy to clean. When group housing swine, troughs are
commonly used. Attention should be paid to competition; there
should be enough space at the trough for each individual animal.
Nevertheless, differences in feed uptake may occur when feeding
from troughs, with a differentiation in body-weight development
as a result. Hence, trough feeding is less suitable for the labo-
ratory.
Sheltered and outdoor housing is unsuitable in a research
setting because of uncontrolled environmental conditions and
the risk of infection. In regions with mild climatic conditions,
raising pigs in huts or kennels on pastures is gaining in popu-
larity. When obtaining swine from agricultural sources, inquiries
must be made about housing type since outdoor swine without
exception need to be treated with antihelminthics when arriving
at the laboratory.
Space guidelines for swine are described by the National
32 33
Research Council and the European Council Directive. Since
no consensus exists among the guidelines, common sense has
to be applied when housing swine. The animals should be "pro-
vided with housing, environment, degree of movement, food,
water and care which are appropriate to their health and well-
being. Restrictions to the physiological and behavioral needs of
experimental animals should be limited to the absolute mini-
33
mum." In general, less space is given to swine in agriculture
than is recommended for research swine. Space recommenda-
tions for research swine are given in Table 2.1.
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Fig. 2.3 Feeding trough for group feeding of newly weaned min-
iature swine
TABLE 2.1: SPACE RECOMMENDATIONS FOR SWINE.32
Floor area
Number of swine Floor area per per animal
per enclosure Weight (kg) animal (ft2) (m2)
1 <15 8.0 0.72

15-25 12.0 1.08
25-50 15.0 1.35
50-100 24.0 2.16
100-200 48.0 4.32
>200 >60.0 >5.40
2-5 <25 6.0 0.54
25-50 10.0 0.90
50-100 20.0 1.80
100-200 40.0 3.60
>200 >52.0 >4.68
>5 <25 6.0 0.54
25-50 9.0 0.81
50-100 18.0 1.62
100-200 36.0 3.24
>200 >48.0 >4.32
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environmental conditions
Elements of environmental conditions are temperature and

humidity, ventilation, illumination and noise.
Temperature and Humidity

Since swine have relatively sparse hair and lack sweat glands,
they are sensitive to temperature fluctuations and extreme tem-
peratures. Especially when swine are housed on grid floors
without bedding, flawless temperature control of the facility is
necessary. Optimum environmental temperatures for swine vary
with age. Newborn swine thrive best at temperatures of 30-38 C
(86-100 F). This is achieved by partial floor heating in the
7
farrowing pen, with the addition of a heat lamp.
Swine are best housed at the thermoneutral temperature. At
this temperature, the relative humidity appears to be unimpor-
tant. Energy conversion is not influenced by the relative humid-
ity at the thermoneutral temperature, which was found to be
29 C (84 F) in juvenile (6-8 weeks old), 24 C (75 F) in young
(14-16 weeks old), and 17.4 C (63 F) in adult (34-36 weeks
34
old) miniature swine. These figures apply to swine generally,
but swine housed on raised grid floors without bedding should
not have temperatures lower than 20C (68 F) because of an
expected higher heat loss. The relative humidity should be main-
tained at 50-70%.
Ventilation
Ventilation is essential to keep the concentration of potentially
harmful gases low, especially in densely stocked quarters. Con-
centrations of NH3 and H2S should not exceed 10 ppm and 5
ppm, respectively, and CO2 levels should not rise beyond 0.15
vol-%. However, air circulation should not exceed 0.2 to 0.3 m/s
7
for adult animals, or 0.1 m/s for piglets.
Generally, a ventilation rate of 10-15 changes per hour with
fresh air is recommended, but the dimensions of the room and
the number of animals present need to be considered, especially
to prevent overventilation as swine are sensitive to draft. On the
other hand, underventilation will lead to a raised environmental
temperature and increased levels of noxious gases.
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Illumination
A light-dark cycle of 12 hours is usually applied to swine, with
the lights switched on from 6 a.m. to 6 p.m. A light intesity of
100 lux is appropriate, but in the mating quarters of breeding
facilities, light intensity should be 200 lux, with the lights on
from 6 a.m. to 8 p.m.
Noise
Swine are relatively insensitive to noise. As a matter of fact, they
are quite noisy themselves, and it is recommended that staff
wear hearing protection when handling swine. However, sudden,
explosive noises should be avoided since these induce fright.
environmental enrichment
Swine are lively animals. Although they spend 70 to 80 percent

of their time lying or sleeping, during the remaining time they
are actively strolling around, exploring, and rooting. When given
the space, swine are clean in their habits, choosing specific sites
for defecation and urination while keeping their sleeping areas
dry. The availability of clean, dry straw contributes substantially
to the well-being of swine. Straw provides comfortable bedding,
and keeps the animals occupied with rooting and chewing activ-
ities. Unless experimental conditions require otherwise, the best
way of accommodating swine and miniature swine is by housing
them in groups of up to 10 or 15 animals in spacious pens with
straw-covered floors.
Group Housing
Social grouping and the establishment of a social hierarchy are
behavioral traits typical for swine. These behavioral patterns
should be considered when housing swine. If possible, individual
housing of swine should be avoided. When group housing swine,
uniformity of the group must be observed, and trough space
must be sufficient to permit all animals to feed at the same
time. Ideally, partitions should be provided, enabling weaker
individuals to avoid the more aggressive ones. Group size should
not exceed 10 to 15 animals, otherwise no lasting hierarchy will
1999 CRC Press LLC

be established. If possible, groups should be kept together. When

the animals have to be regrouped, the extent of fighting may be
minimized by bringing unfamiliar animals together just before
feeding or sleeping time, preferably in a newly cleaned pen. The
individual scent of all animals of the group may be camouflaged
with a strong fragrance (mint oil, cresol), and in critical cases
animals can be tranquilized before being brought together.
Adult boars are solitary, and individual housing is appropri-
ate. Nonetheless, it is possible to group house boars, with the
exception of particularly aggressive individuals, provided they
have been reared together or have been given the opportunity
to get accustomed to each other under unconfined conditions.
Barrows can be group housed under similar conditions to those
of females.
Fig. 2.4 Woodshavings or straw and a hard plastic ball are

excellent environmental enrichment for swine since they stimu-
late rooting behavior (Photo courtesy of Pfizer Central Research)
Individual Housing
At the laboratory, individual housing is common. As described
before, individually housed animals should have visual, olfac-
torial, and auditory contact with other swine to prevent them
1999 CRC Press LLC

from being socially deprived. To a large extent, swine become

35,36
attached to humans, especially when housed individually,
and daily positive contact with staff should be included in the
37
animal care program.
Most important to swine is the provision of items that can be
manipulated, especially when no bedding is provided, to satisfy
the needs of chewing and rooting. The following items can be
considered as elements of environmental enrichment:
a chain suspended from the side of the pen
a hayrack with straw or hay
a nylon brush or broom head attached to fencing
a heavy ball, plastic crate, or plastic turf mat placed on
the floor
A chain and straw or hay in a hayrack primarily satisfy the
need for chewing, but they also provide material for manipula-
tion with the snout. A brush or broom head attached firmly to
the fencing is used for rubbing against, but also for biting,
whereas balls, crates, or turf mats are used for satisfying the
need for rooting. For all elements of enivronmental enrichment
it is essential to allow a good level of sanitation. The animals
quickly lose interest if the items get soiled, especially items
placed on the floor of the pen. To avoid soiling and preserve the
novelty of the items, balls, crates, or turf mats should only be
given to the animals for a limited period daily.
nutrition
Most publications relating to swine nutrition focus on optimal

utilization of nutrients with an eye on efficient growth, since
feed accounts for two-thirds of the costs of producing market-
weight swine.38
Although laboratory swine nutrition is basically similar to
production swine feeding, it may be desirable to control weight
gain. Therefore, restricted feeding is often applied at the labo-
ratory. Moreover, miniature swine are prone to obesity and,
consequently, restricted feeding is necessary to maintain normal
physiological conditions in miniature swine. There are indica-
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Fig. 2.5 Pressed and extruded feed pellets
tions that nutrient requirements of miniature swine differ from

those of other swine,39 but until further evidence has been
produced, nutrient requirements of swine should be used as a
basis for miniature swine nutrition.40, 41
Nutrient Requirements
The National Research Council (NRC) provides detailed informa-
tion on the composition of swine diets, including energy, protein
and amino acids, minerals and vitamins, and diet formulation.
However, the given nutrient requirements are minimum stan-
dards when feeding ad libitum and should not be considered
recommended allowances.16 Table 2.2 gives an overview of the
nutrient requirements of swine with body weights between 5
and 80 kg.
Swine are able to utilize high-fiber diets because of fermen-
tation in the cecum and large intestine. However, fiber levels
over 7-10% inhibit growth. Dietary fiber also has an effect on
the passage of food through the intestines, and diets with a high
fiber content prolong the gastrointestinal transit time. fiber lev-
els of up to 15% have no effect, but levels exceeding 15% will
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TABLE 2.2: NUTRIENT REQUIREMENTS OF SWINE WITH BODY WEIGHTS

FROM 5 TO 80 KG.16
Body weight MEa content of Expected feed Crude

(kg) diet (MJ/kg) intake (g/day) protein (%)
5-10 13.6 500 23.7

10-20 13.6 1,000 20.9
20-50 13.6 1,850 18.0
50-80 13.6 2,575 15.5
a) Metabolic energy; 1 MJ = 240 kcal (13.6 MJ/kg = 3,265 kcal/kg)
increase the transit time. Especially when roughage, such as

straw or hay, is fed, gastric emptying and intestinal transit time
are significantly prolonged.42 Low energy diets, especially meant
as maintenace diets for miniature swine, usually have a rela-
tively high fiber content of 13-15%.
The minimum level of minerals and vitamins is well defined,16
and commercial diet producers may be expected to have
included sufficient mineral and vitamin premix to cover the
requirements of swine. However, when comparing levels from
catalogue values and analysis reports, a disturbing discrepancy
may be found within and between brands.39
Feeding Levels
The feed intake of swine, as in all mammals, depends on the
energy concentration of the feed. However, when the equation
for estimated energy intake with ad libitum feeding of swine is
compared to the equation for energy intake used for interspecies
comparison, based on metabolic weight, swine have a much
larger energy intake than expected from this equation.
The general practice in swine feeding is ad libitum feeding.
With this, modern production swine grow 2-3 kg (4.4-6.6 lbs)
per week, so that they weigh 80-100 kg (175-225 lbs) at the age
of 5-7 months when, generally, they are slaughtered. This enor-
mous weight increase may be undesirable at the laboratory.
Therefore, restricted feeding is often applied at research facili-
ties. In miniature swine, restricted feeding is essential since they
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Fig. 2.6 The expected metabolizable energy (ME) intake for

growth can be calculated with the equation for interspecies
15 0.75
comparison, based on metabolic weight (ME=1.20*W ).
38 0.63
However, the best fitting equation for swine (ME=2.52*W )
results in a higher expected energy intake
easily become obese when fed without restriction. From studies

in rodents, it has become clear that a feeding level of 60% of
the ad libitum food intake is sufficient to prevent obesity, fulfills
the nutrient needs, and leads to a longer, healthier life as
compared to ad libitum feeding.43 This may be applied to labo-
ratory swine as well, but more often restricted feeding with a
low energy diet is applied to allow the animals a satisfying food
volume intake. Whereas a standard swine diet has a metabolic
energy content of 13.6 MJ/kg (3,265 kcal/kg), a typical low-
energy diet has a metabolic energy content of 9.5 MJ/kg (2,275
kcal/kg). Feeding levels can be found in Table 2.3.
Clean drinking water should be available at all times. Therefore,
automated watering systems (nipple or bowl type) are recom-
mended. Although water is essential, suprisingly little research
has focused on the water requirements of swine. True water
consumption is often overestimated since swine like to play with
water, and wastage is often not taken into account.16 Approxi-
1999 CRC Press LLC

TABLE 2.3: FEEDING LEVELS.

Expected Daily Restricted Low Energy
Body weight Energy Intake Feeding Feeding Feeding
(kg) (MJ/day)a (g/day)b (g/day)c (g/day)d
5 4.00 290 175 255

10 6.75 500 300 425
20 11.35 835 500 715
50 22.55 1,660 995 1,425
80 32.10 2,360 1,415 2,025
a) ME = 1.2 W0.75 (MJ/day)15

b) metabolizable energy density of diet = 13.6 MJ/kg (3,265 kcal/kg)
c) 60% of expected energy intake with a diet of ME=13.6 MJ/kg (3,265
kcal/kg)
d) 60% of expected energy intake with a diet of ME= 9.5 MJ/kg (2,275
kcal/kg)
mately 120 ml/kg water are used by growing swine fed a dry
pelleted diet.16, 44 The delivery rate of water via automated water-
ing devices should be about 0.5 l/min. If automated watering
devices are not available, the usual practice is to mix water with
the diet and refill the trough with water after the swine have
finished eating.
sanitation
Sanitation is important to maintain the health of swine. Excreta
and food remains are a substrate for microbial growth and attract
insects and rodents which could act as vectors for diseases. There-
fore, pens should be cleaned frequently, but sanitation should be
carried out with minimal use of disinfectants to prevent chemical
contamination of the animal environment.45
Frequency
Daily removal of excreta is good practice. When swine are housed
on solid floors with bedding, removal of soiled bedding is essential.
Soiled bedding represents the largest volume of waste material,
and could lead to capacity problems when disposing waste in bags
or containers.
1999 CRC Press LLC

Fig. 2.7a Watering device for young miniature swine.
Fig. 2.7b Watering device for adult miniature swine.
1999 CRC Press LLC

Swine housed on grid floors usually press feces through the

grids with their hooves, whereas urine runs through. Under the
grid floor, a sewer canal may be present through which the
excreta can be flushed away. When larger numbers of animals
are present, animal rooms for swine should be constructed with
a manure cellar under the grid floors. Here, excreta accumulate
and are pumped to a large basin outside the facility at regular
intervals. Grid floors should be checked daily, and feces accu-
mulated in corners should be scraped away.
Pens should be washed weekly, although pens with grid floors
are usually washed at longer intervals to prevent excessive
amounts of liquid manure. A mild disinfectant may be used.
Disinfectants should be rinsed away and solid floors swabbed
dry before allowing the animals to return to their pens.
Pens should be sanitized thoroughly on a monthly basis.
High-pressure cleaning is commonly used in swine facilities.
Because of aerosol formation, high-pressure cleaning should be
carried out without additives to the water. A detergent or disin-
fectant is usually added to low-pressure water to rinse with after
high-pressure cleaning. Detergents or disinfectants should be
rinsed away and solid floors swabbed dry before allowing the
animals to return to their pens.
Methods
Sweeping should be minimized to prevent dust formation. Floors
of pens, corridors, and utility rooms should be washed and
swabbed dry after gross debris has been removed. Staff working
with soiled bedding, especially wood shavings, should wear dust
masks for protection.
High-pressure cleaning should include floors, walls, fencing,
bowls and troughs, drinking devices, and items for environmental
enrichment. Detergents or disinfectants should not be used before
high-pressure cleaning, nor should they be added to high-pressure
water because of the risk of exposure to aerosols during high
pressure cleaning. Staff should wear protective clothing (water-
tight suits or aprons), fluid shield masks, and hearing protection.
A wide range of detergents and disinfectants are available, and
suitable detergents and disinfectants should be chosen based on
experience and what is already present at the facility. An overview
of disinfectants and disinfection is given by Russell et al. (1984).46
1999 CRC Press LLC

transportation
Transportation is stressful for swine, and gentle handling is

necessary. Since swine suffer from travel sickness, animals
should be deprived of food 12 hours prior to, and during, trans-
portation. If animals are transported over long periods, breaks
should be included to offer the animals water at least every 6
hours. Hot, humid conditions during transportation should be
avoided, as well as low temperatures and drafts. Ideally, clima-
tized vehicles should be used to maintain environmental condi-
tions similar to those at the animal facility.
Fig. 2.8 Vari Kennel transport kennel for swine under 25 kg
Swine are generally transported freely standing in a truck or

trailer. A space of 0.5 m2/100 kg (2.5 ft2/100 lbs) body weight
should be allowed. Floors must not be slippery; a slatted floor
covered with wood shavings is commonly used. Large loading
surfaces should be avoided, or should be subdivided by parti-
tions.
1999 CRC Press LLC

Young swine or miniature swine can be transported in por-

table dog kennels (e.g. Vari Kennel) or custom-made crates.
Floors should be covered with wood shavings. Straw is not as
suitable as wood shavings since it does not absorb as well. There
should be openings for fresh air, and sufficient space to lie down
comfortably. Requirements for swine transportation are
described in manuals for transportation of live animals by road47
and air.48
Fig. 2.9 Identification of swine with ear notches and ear marks.
To the left, the identification system for Gttingen minipigs
consists of an earnotch system which allows numbering from
0-99, plastic earmarks, and an intramuscularly implanted tran-
sponder. To the right, an animal marked number 54.
record keeping
Record keeping requires individual identification of animals.

Swine may be identified with ear notches, ear tatoos, ear tags,
neck bands, or intramuscular electronic transponders. For tem-
porary marking of swine, colored markers or spray can be
applied on the skin.
Individual animal records should contain the animal's iden-
tification number, identification numbers of the parents (if
known), and pen number. Body-weight development and medical
treatment should be recorded as well, and preferably also infor-
mation about feed intake, abnormalities, and research proce-
dures.
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3
management and quality
assurance
Management of swine at the laboratory should aim at achieving
the highest possible scientific outcome of research on swine.
Therefore, it is essential to standardize production and mainte-
nance of swine, as well as to assure the quality. Quality assurance
of laboratory swine has especially been concerned with microbi-
ological and genetic factors. Furthermore, the status of the swine
as an important production animal requires that certain legal
demands must be fulfilled.
microbiological management and quality
Impact of Infections on Animal Research using Swine

In Chapter 4, information about important infections in laboratory
swine is given. Such infections may have an impact on experi-
ments with swine in various ways. Basically, the impact may be
divided as follows:
Pathological changes, clinical disease and mortality.

Clinically apparent disease is mostly due to bacterial infections,
such as Actinobacillus pleuropneumoniae, which causes severe
lung disease. Animals suffering from such a disease are seldom
used for experiments, but infections may have a severe economic
1999 CRC Press LLC

impact on laboratory swine breeding and maintenance. However,
some infections induce severe pathological changes in the animals
which may not be discovered until during the experiment. Myco-
plasma spp. and Haemophilus parasuis may both cause polyser-
49
ositis, and surviving swine consequently have adhesions in the
thorax and abdomen which are often not discovered until the
swine has already been anesthetized and has undergone laparat-
omy.
Immunomodulation.
The immune system may be modulated by spontaneous infections
in the absence of clinical disease, an effect which may be sup-
pressive or activating or both at the same time, but on different
parts of the immune system. As a general rule of thumb, all viruses
should be regarded as possibly being immunosuppressive, one of
the reasons being the viremic phase in the pathogenesis of many
viral infections during which cells of the immune system may be
infected. The immunological impact of African swine fever virus
has been intensively studied, and it has been shown that changes
50
in the immune system persist after recovery from infection.
African swine fever is not common in herds supplying swine for
experiments, but more frequently occurring viruses such as influ-
enza viruses may have a serious impact on the immunology of
51
the animals, a phenomenon which is well-known from other
animal species.
Physiological modulation.
Some microorganisms have a specific effect on enzymatic, hema-
tological, and other parameters monitored in the animal during
an experiment. Organic function disturbances may change the
outcome of the experiment without the knowledge of the scientist,
e.g., the altered function of the liver caused by some spontaneous
hepatic infections may influence pharmacokinetics. Infection with
Streptococcus suis, for instance, decreases single dose clearance
52
but increases multiple dose clearance of sulfadimidine.
Competition between microorganisms within the

animal.
Spontaneous infections in an experimental infection model may
compete with the experimental infection, which in the worst
cases may fail. Gnotobiotic- or microbiologically-defined swine
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can be experimentally infected with Helicobacter pylori, while
53
conventional swine cannot. Such a difference between micro-
biological categories of animals may be explained by natural
infection with related agents, as species-specific Helicobacter
54
spp. have been isolated in swine. Infections with species other
than Helicobacter may also play a role.
Interference with reproduction.

For the breeder, changes in the fertility of the animals may be
the cause of serious trouble. Infections giving rise to clinical
disease in a major part of the population are very likely to reduce
the fertility, and it is also quite obvious that infections such as
55
rotaviruses leading to high mortality in neonates, will reduce
the outcome of breeding or disturb experiments using newborn
swine. Direct effects of the infection on reproduction, such as
the change in sex hormones, pathological anatomical changes
in the reproductive tract, or infection of the embryo causing
abortion and stillbirths are also observed, e.g., with common
viruses such as porcine parvovirus and the enterovirus SMEDI.56
Reproduction studies, in which the absence of such infections
have not been documented, may be prone to criticism.
Interference with oncogenesis.

Infectious agents may either induce cancer, enhance the carci-
nogenic effect of certain compounds, or reduce the incidence of
cancer in laboratory animals, and opportunistic pathogens may
become pathogenic in animals with cancer, e.g., swine with
lymphosarcomas are more likely to die from colibacillosis than
swine without lymphosarcomas.57
Contamination of biological products.

Microorganisms present in the animal may contaminate samples
and tissue specimens such as cells, sera, etc. This may compli-
cate in vitro maintenance of cell lines, and may interfere with
experiments performed on cell cultures or isolated organs. Fur-
thermore, the reintroduction of such products into an animal
laboratory will cause a risk to the animals kept in that labora-
tory. In fact, some of the mycoplasmae which complicate main-
tenance of cell lines are porcine mycoplasmae originating from
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either the use of porcine serum in the media, or the porcine
origin of the cells to be grown.58
Zoonotic Diseases
Some important zoonoses are listed in Table 3.1. It should be
noted that zoonoses of porcine origin in laboratory animal staff
are rare. The major risk seems to be development of erysipelas
after contact with swine infected with Erysipelothrix rhusio-
pathiae.59
The potential future use of swine as organ donors for human
xenotransplantation has created a new term, xenozoonosis,60
i.e., infections which may pass with the organ from the animal
donor to the human recipient. More information about the risk
of porcine retroviruses for humans is needed to evaluate the
risk connected with porcine-human xenotransplantation. It is
obvious that porcine infections already known to possess a
zoonotic potential should be a matter of concern. However, these
are well-defined and diagnostic and preventive tools are well-
developed, while there is little knowledge of the risks connected
with the xenotransplantation entry port. It is conceivable that
porcine viruses may mutate into a human variant, maybe with
a lethal effect. If so, this may have implications not only for the
individual patient, but for mankind as such. Obviously, empha-
sis has mostly been placed on retroviruses. Xenotransplant
recipient patients need immunosuppression, and, therefore, it
is of vital interest to know whether immunosuppression will
allow non human retroviruses to propagate in humans. Little is
known about exogenous retroviruses in swine but, in fact, type
C retroviruses have been found in the blood of certain strains
of miniature swine after exposure to radiation,61 and it is known
that porcine retroviruses may infect human cell lines.62 Herpes
viruses may be another concern. The maccaque herpes virus
type B can cause fatal encephalitis in humans, and this may
also be so for other types of herpes viruses, e.g., the porcine
Aujeszkys virus. Porcine Aujeszkys virus is known to be fatal
in other animal species, such as ruminants. Also, rotaviruses,
which are extremely common, even in purpose-bred miniature
swine,63 may be potential xenozoonotics. Gnotobiotic piglets can
be experimentally infected with rotaviruses of a human nature,64
and it has been shown that some rotaviruses may be shared by
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TABLE 3.1: PORCINE INFECTIONS WITH A ZOONOTIC POTENTIAL.
Risk for
Agent Symptoms Transmission to man research
staff
In pigs In man
Brucella suis Mostly no symptoms. Severe fever and disabling Direct contact with Low
Classical signs are lesions of the spine which tissues, blood, urine,
abortions, infertility, weak may become lethal vaginal discharges, or
piglets at birth, infection of aborted fetuses and
the testes and arthritis placentas from infected
animals
Campylobacter jejuni Diarrhea or no symptoms Diarrhea Fecal contamination of Low
human food
Eschericia coli (only Neurologic symptoms, Similar to the pig, Fecal contamination of Low
certain strains edema of the eyelids, occassionally damage to human food
causing porcine occassionally edema of the the heart valves, or
edema disease) neck and abdominal skin sudden death
Erysipelothrix Fever, arthritis, often Similar to the pig, Contact with infected High
rhusiopathiae squarish erysipeloid lesions occassionally damage to pigs
(pinpoints to > 3 inches) the heart valves, or,
sudden death
Leptospira spp. Normally none, in some Haemorrhagic fever Contact with porcine Low
cases abortions urine
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TABLE 3.1: PORCINE INFECTIONS WITH A ZOONOTIC POTENTIAL.
Risk for
Agent Symptoms Transmission to man research
staff
In pigs In man
Salmonella spp. Diarrhea Diarrhea Fecal contamination of High

human food
Taenia solium None Brain seizures, muscle Intake of insufficiently Low
pain and weakness, heart cooked pork
failure, sometimes
sudden death due to
development of
cysticercs.
Trichinella spiralis None Muscle encapsulations Intake of insufficiently Low
resulting in weakness cooked pork
and muscle pain
Mycobacterium bovis, None (granulomas may be Tuberculosis Inhalation and Low

M. avium, and M. found during necropsy) ingestion
tuberculosis
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swine and humans, e.g., the Gottfried porcine rotavirus.65 Sim-
ilar questions may be raised about bacteria such as Streptococci.
Legal Regulations
Most Western countries have regulations concerning import and
export of live animals. OIE (Office International de pizooties),
the International Office of Epizootics, is an organization of indi-
vidual member countries that registers infectious diseases
worldwide, sets standards, and issues guidelines on how to
prevent the spread of infectious animal diseases.66 OIE is
responsible for the administration of the International Animal
Health Code, according to which the member countries have
certain responsibilites such as warning each other if any of the
diseases listed in Table 3.2 are diagnosed in a member country.
Swine are especially subject to strict regulations since pork
production is essential for the national economy in several coun-
tries. According to U.S. regulation, the Secretary of Agriculture
has "authority to make such regulations and take such mea-
sures as he may deem proper to prevent the introduction or
dissemination of the contagion of any contagious, infectious, or
communicable disease of animals ... from a foreign country into
the United States or from one State ... to another." Such rules
are a common part of agricultural legislation in most Western
countries.
In order to achieve these goals, national departments of agri-
culture in the OIE member countries run mandatory health
programs aimed at irradication of OIE-reportable diseases such
as brucellosis, foot-and-mouth disease, and swine fever, only
allowing import and export of swine and porcine products under
strict state veterinary control. Therefore, prior to import and
export of swine, one should always contact the national or local
veterinary authorities to ensure that licenses are granted and
that the swine are provided with all necessary certificates.
Regulations that cover swine in biomedical research in the USA

are:
Animal Welfare Act (U.S. Department of Agriculture,
7USC 2131) and their associated regulations (9 CFR:
Parts 1,2, and 3)
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TABLE 3.2: REPORTABLE INFECTIOUS DISEASES OF SWINE REGISTERED
BY THE INTERNATIONAL OFFICE OF EPIZOOTICS (OIE).
List A Diseases List B Diseases
Definition: Definition:
Transmissible diseases which have the Transmissible diseases which are
potential for very serious and rapid considered to be of socio-economic
spread, irrespective of national borders, and/or public health importance within
which are of serious socio-economic or countries and which are significant in the
public health consequence and which are international trade of animals and animal
of major importance in the international products.
trade of animals and animal products.
Foot and mouth disease Anthrax
Vesicular stomatitis Aujeszky's disease
Rift Valley fever Leptospirosis
Bluetongue Rabies
African swine fever Avian diseases
Classical swine fever Atrophic rhinitis of swine
Enterovirus encephalomyelitis
Porcine brucellosis
Porcine cysticercosis
Porcine reproductive and respiratory
syndrome
Transmissible gastroenteritis
Trichinellosis
Public Health Service Policy on Humane Care and Use of

Laboratory Animals (Health Research Extension Act of 1985)
for studies funded by the U.S. Government
The principles for implementation of the Public Health Service
policy are those described in the Guide for the Care and Use of
Laboratory Animals.32
The Animal Welfare Act and the Public Health Service Policy
on Humane Care and Use of Laboratory Animals do not apply
to swine used in agricultural research. Here, the Guide for the
Care and Use of Agricultural Animals in Agricultural Research
and Teaching can be used as guidance.67
Precautions to Prevent Infections

In several countries, organizations to ensure the health of farm
swine exist. National organizations such as the National SPF
Swine Accreditation Agency in the United States have, since the
1999 CRC Press LLC

late fifties, set up systems for swine production according to a
three-step principle:
1. Production of germ-free animals by rederivation tech-
niques, i.e., Caesarean section or embryo transfer
2. Upstart of a breeding colony on the basis of the rederived
animals in a protected (barrier) environment
3. Regular screening of the colony for the presence of cer-
tain agents (health monitoring)
Rederivation.
Germ-free swine may be produced by removing them aseptically
from the uterus by hysterectomy and rearing them in isolators.68
In the isolators they may be associated with a specific flora. The
term gnotobiotic covers germ-free animals as well as animals
with a specific flora. Gnotobiotic swine are used for immuno-
logical studies such as natural and adaptive immunity and early
antibody synthesis, radiation studies, studies of monoassocia-
tion with certain bacteria, and studies of parenteral nutrition.69,
70,71 Germ-free swine have a lower peripheral blood leucocyte
count than conventional swine, although they have an increased

number of peripheral T-cells, a lower percentage of neutrophilic
granulocytes, lower total serum protein, and higher serum albu-
min and beta-globulin levels.72
An alternative to Caesarean section is embryo transfer.73 The
piglets will receive the microbiological status of the recipient
mother.
Barrier protection.
As long as the swine are kept in isolators the gnotobiotic status
can be maintained. If the swine are used for the upstart of a
breeding colony, housed under conditions protecting them
against certain agents for which a monitoring system is oper-
ated, terms such as minimal disease (MD), specific pathogen-
free (SPF), and microbiologically defined swine are used.
Meat-producing SPF systems consist of various levels of
herds; i.e., animals derived from Caesarean sections are used
for the upstart of a primary SPF herd, which may deliver swine
for breeding in a secondary SPF herd. No further animals are
introduced into primary herds.
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Swine produced under barrier protection equivalent to what
is applied when breeding laboratory rats and mice are referred
to as microbiologically defined.27,74 Microbiologically defined
swine have improved the possibilities of using swine for research,
not only in toxicology,75,76,77 but also in more specific research
such as studies of Helicobacter pylori infection.78 Microbiologi-
cally defined swine seem to differ in serum and hematology
values from conventional swine in the same way as described
for gnotobiotic swine above.20
Some quarantine and barrier demands are also fulfilled in the
production of SPF and MD swine, although in general not as
strict as for microbiologically defined swine (Table 3.3). The SPF
production method was first applied in agricultural swine farm-
ing, where it was used to eliminate infections with a negative
impact on the farmer's economy. However, SPF swine have also
been widely used for experimental purposes because they are
free of mycoplasmae. The term minimal disease (MD) often covers
SPF swine colonies with reinfection of some of the regulated
pathogens. This term may be used for former SPF colonies
infected with, for example, Mycoplasma hyopneumonia. Swine
that are neither SPF nor microbiologically defined are called
conventional.
TABLE 3.3: TYPICAL HOUSING CONDITIONS FOR DIFFERENT CATEGORIES

OF PIGS FOR EXPERIMENTAL PURPOSES.
Conventional Specific Pathogen Microbiologically

Free (SPF) defined
Minimal Disease
(MD)
Caesarian originated - + +
Barrier:
Quarantine - + +
regulation
Change of dress - + +
Shower in - - +
Decontamination of:
Diet - - +
Equipment - - +
Water - - +
Absolute filtered - - +
ventilation
Health monitored - + +
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Health monitoring.
Table 3.4 gives some examples of infections covered by the SPF
term, although it should be remembered that organizations in
different countries work with slightly different lists. Some asso-
ciations of laboratory animal science, e.g., the Scandinavian
Society for Laboratory Animal Science79 or the Federation of
European Laboratory Animal Science Associations (FELASA)80
have issued guidelines for advanced health monitoring of swine
for experiments. Such guidelines recommend monitoring for a
range of agents. Some commercial vendors specialized in pur-
pose-breeding of swine for research have set up their own sys-
tems which may differ slightly from the guidelines (Table 3.5).
TABLE 3.4: INFECTIONS WHICH MAY BE COVERED UNDER THE TERM

SPECIFIC PATHOGEN FREE (SPF).81,82
Disease Pathogen
Morbus Aujeszky (Pseudorabies) Herpesvirus (Aujeszkys virus)
Pneumonia Mycoplasma hyopneumoniae

Actinobacillus pleuropneumonia
Swine dysentery Serpulina hyodysenteria
Transmissible gastroenteritis Coronavirus (TGE)
Atrophic rhinitis Pasteurella multocida
Sarcoptic mange Sarcoptes scabiei
Porcine Reproductive and Respiratory PRRS virus

Syndrome
In breeding colonies, health monitoring is based on random

representative samples. This means it is assumed that a few
animals can be sampled for examination but the results can be
used to describe the entire colony. If one animal is found to be
infected with a certain organism, the entire colony is considered
infected with that particular organism. Often the opposite is also
assumed, i.e., if no animals are found to be infected with a certain
organism, the entire colony is considered free of that particular
organism. This, however, requires the use of a statistically valid
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sample size.83 The sample size may be calculated using the
equation in Figure 3.1.
As soon as a sample has been taken, it becomes historical.
By comparing two samplings taken at a certain interval, the last
sampling will visualize whether changes have occurred between
the two samplings.
A random sample of animals is only predictive for the micro-
biological status of other animals if these animals have some
kind of contact with each other. Therefore, it is essential to
define the microbiological entity, i.e., a definition of the group
of animals for which a sample is predictive. A simple one-room
unit used for breeding in a commercial establishment will nor-
mally have its own staff and barrier to separate it from all other
units; each of these separate units should therefore be regarded
as a separate microbiological entity. However, if the unit is
separated into different rooms that are all served by the same
staff and get their supplies through a common barrier, it is hard
to define the microbiological entity; it should be noted that the
more subunits included, the higher the uncertainty of the sam-
pling. If the infection is only found in one subunit, the prevalence
is "diluted," which may not be taken into consideration when
calculating theI sample size.85
Most standards for health monitoring also demand regular
clinical inspections by a trained veterinarian. In some systems
vaccines and/or antiparasitics are banned, while they are fre-
quently applied in other systems. This should be checked with
the vendor. Prior to any purchase of swine for experimetal pur-
poses a health report should be retrieved from the vendor.
Common Findings in Health Monitoring

In the majority of conventional swine, antibodies against parvo
and influenza viruses as well as H. parasuis are found. Further-
more, although less common, antibodies against porcine coro-
naviruses, hemagglutinating encephalomyelitis virus, porcine
reproductive and respiratory disease viruses, and all serotypes
except Types 7 and 8 of A. pleuropneumoniae and Mycoplasma
hyopneumoniae are found. Bacteriological, fungal, and parasito-
logical examinations often reveal the presence of A. pleuropneu-
moniae, Bordetella bronchiseptica, Clostridium perfringens,
Eubacterium suis, H. parasuis, Pasteurella multocida, Salmonellae,
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TABLE 3.5: INFECTIONS INCLUDED IN SOME PROGRAMS FOR HEALTH MONITORING OF MICROBIOLOGCIALLY DEFINED PIGS.
Ellegaard Gttingen Charles River

ScandLAS79 FELASA80 Minipigs85 Laboratories86
VIRAL INFECTIONS
Africian swine fever No If present in country Cons. abs. Cons. abs.
Morbus Aujeszky Yes If present in country Yes Yes
Encephalomyocarditis virus No If present in country No No
Hemagglutinatinating Yes If present in country Yes No
Encephalomyelitis
Porcine coronaviruses No If present in country Yes No
Porcine cytomegalovirus No If present in country No No
Porcine Influenza Yes If present in country Yes No
Porcine Parvovirus Yes If present in country Yes No
Porcine Reprodutive & Respiratory No If present in country Yes Cons. abs.
Syndrome
Porcine Rotavirus Yes If present in country Yes No
SMEDI Yes If present in country Cons. abs. No
Swine fever Cons. abs. If present in country Yes Cons. abs.
Teschener disease Yes If present in country Cons. abs. Cons. abs.
BACTERIAL AND FUNGAL

INFECTIONS
Actinobacillus pleuropneumoniae Type 2,3,4 All types All types All types
Actinomyces pyogenes On request On request No Yes
Bordetella bronchiseptica Yes Yes Yes Yes
Brucella suis On request On request Cons. abs. Yes
Campylobacter spp. Yes No Yes Yes
Clostridium perfringens Yes On request Yes Yes
Erysipelothrix rhusiopathiae Yes Yes Yes No
Eubacterium suis Yes Yes Yes No
Helicobacter spp. No No Yes No
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TABLE 3.5: INFECTIONS INCLUDED IN SOME PROGRAMS FOR HEALTH MONITORING OF MICROBIOLOGCIALLY DEFINED PIGS.
(continued) Ellegaard Gttingen Charles River

ScandLAS79 FELASA80 Minipigs85 Laboratories86
BACTERIAL AND FUNGAL INFECTIONS

Haemophilus parasuis Yes Yes Yes Yes
Klebsiella pneumoniae On request No No Yes
Microsporum spp On request On request Yes No
Mycoplasma hyopneumoniae Yes Yes Yes Yes
Pasteurella multocida Toxin prod. Toxin prod. Yes Yes
Salmonellae Yes Yes Yes Yes
Staphylococcus aureus No No No Yes
Staphylococcus hyicus Yes Yes Yes No
b-hemolytic streptococci Yes Yes Yes Yes
Streptococcus pneumoniae Yes No Yes No
Streptococcus suis Yes Yes Yes No
Trichophyton spp On request On request Yes No
Yersinia enterocolitica Yes Yes Yes No
PARASITOLOGICAL INFECTIONS
Arthropods Yes Only sarcoptes Yes Yes
Helminths Yes Yes Yes Yes
Enteric protozoa Only coccidiae Only coccidiae Only coccidiae Yes
Toxoplasma gondii Yes Yes Yes Yes
On request: The guidelines demand that the producer screens for the agent if requested by the user.
Cons. abs.: Considered absent; some agents are not included in the program, because they are irrellevant due to
national health programs
If present in country: The infection should only be included in the program if it has not been eliminated by national health
programs
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Fig. 3.1 Sample sizes for health monitoring in relation to the
expected prevalence of the monitored infection. If the colony size
is small, i.e. less than 10.000, or the expected prevalence low,
i.e. under 20%, the population size is of some impect on the
sample size. If this is not the case, the sample size (S) can be
83
calculated from following equation :
S > log C.
(1-(p*N1))
C= accepted risk of a false negative diagnosis; N1= sensitivity of
the applied test; p= expected prevalence
Staphylococcus hyicus, S. suis, as well as helminth eggs and

coccidiae.87 SPF swine do not harbour infections such as A.
pleuropneumoniae and Mycoplasma hyopneumoniae, which are
mentioned in the guidelines for this category of swine, but
concerning nonlisted agents there is no guarantee for the
absence of the other abovementioned agents. Swine housed
according to the principles for microbiologically defined animals
have been shown to harbour a lower number of infections than
swine housed according to agricultural SPF guidelines, but also
in microbiologically defined swine, health monitoring may reveal
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the presence of certain agents with a research interference
potential, e.g., rotaviruses.63
genetic monitoring
Genetic monitoring, used as a tool for standardization in labo-

ratory rodent breeding, has not been applied in the same way
to the breeding of swine for research. On the contrary, most
genetic programs are aimed at the development of a research
swine more applicable than those presently available, such as
the selection for a smaller size of Yucatan miniature swine.88
Breeders register certain parameters on a routine basis in order
to use these for selection. Such parameters may include:27,74
weight at birth
growth rate
number of visible ear veins
temper
number of teats
malformations
Recently, genetic maps of the swine genome have been

made.89,90
accreditation
Certain bodies may accredit laboratory animal facilities with

respect to production quality or animal welfare.
AAALAC International
AAALAC International, the Association for Assessment and
Accreditation of Laboratory Animal Care, runs a voluntary
accreditation program in which research institutions demon-
strate that they not only meet the minimums required by law,
but are taking the extra step to achieve and showcase excellence
in animal care and use. Apart from accreditation, AAALAC also
offers independent assessments of animal research programs to
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help institutions to improve their animal care and use practices
continuously. AAALAC International accreditation is common in
the United States, but animal facilities and breeders in other parts
of the world are increasingly seeking AAALAC International
accreditation.
Breeding of common laboratory animal species in European
Union member states is subject to regulations concerning des-
tinational breeding of laboratory animals for research, which
means that all breeders must be licensed by and work under
inspection of the local animal welfare authorities. These regu-
lations, however, do not regulate swine breeding, and therefore,
swine breeders may want to seek AAALAC accreditation instead.
ISO 9000
ISO 9000 is a set of five universal standards for a Quality
Assurance system issued by the International Standardization
Organization (ISO), a worldwide associaton of national standards
bodies. Currently, 90 countries have adopted ISO 9000 as
national standards. The system aims to assure compliance
between the quality of the product and the expectations of the
customer. The less comprehensive standard ISO 9002, the so-
called "Quality SystemModel for Quality Assurance in Produc-
tion, Installation, and Servicing," may be applied to breeders of
laboratory animals. ISO 9000-registered vendors have ensured
that they have a proper quality assurance system. This system
is becoming increasingly important. The overall accreditation is
granted by a national ISO member organization. In the U.S. this
is the American National Standards Institute.
Other Organizations
Several organizations other than AAALAC International and ISO
9000, issue quality directives relevant for laboratory animal
facilities.91 Studies submitted to the Food and Drug Adminis-
tration (FDA) or Environmental Protection Agency (EPA) should
comply with Good Laboratory Practice (GLP). The EN 45000
directive, issued by the ISO, is a quality guide for test, inspec-
tion, and calibration laboratories, whereas production plants
and laboratories working with food and food additives should
comply with the Hazard Analyses Critical Control Points
(HACCP) standards.
1999 CRC Press LLC

4
veterinary care
The veterinary care of swine starts with the arrival of the

animals at the facility. Clinical examination should be a stan-
dard procedure upon arrival. Swine purchased from agricultural
sources usually have no health record, and microbiological sam-
pling should be included as part of the clinical examination.
Swine originating from specialized laboratory swine breeders are
usually provided with a health monitoring report (HMR). The
HMR should be studied for positive findings, and it should be
considered whether positive findings pose a risk for the existing
swine population in the facility. Until results from the clinical
examination are available, swine should be housed in quaran-
tine facilities.
clinical examination of swine92,93
A good clinical examination starts with the history of the indi-

vidual animal. Breed, sex, age, weight, and the animal's identi-
fication number should be recorded, and existing HMR or animal
certificates should be added to the record.
Swine are usually not accustomed to handling, so to avoid
misleading observations of physiological parameters, swine
should be observed as much as possible without handling or
restraint. However, swine arriving at the facility are heavily influ-
enced by transportation, and it should be taken into account
1999 CRC Press LLC

that the animals are excited by the new environment. Posture,
behavior and respiration should be observed prior to restraint.
Diseased swine may have long, rough-haired coats, with the
hair standing up (piloerection). A dog-sitting posture is associ-
ated with respiratory difficulty. Hypothermic swine usually lie
in sternal recumbency with the legs tucked under the body.
Normally, swine lie on their sides, but this is avoided by animals
with heart disease or abdominal pain. Lame swine are reluctant
to rise. Swine in good nutritional states should neither be too
fat nor have observable bony structures in the body. The normal
body temperature is 38-39 C (100-102 F).
A check list for clinical examination of swine is given in Table
4.1.
TABLE 4.1: CHECK LIST OF CLINICAL EXAMINATION OF SWINE.
Condition Desirable Undesirable

body weight normal for breed, age and thin, fat, or obese
sex
skin flat hair coat with a pale, anemic skin,
normal thickness for the thickened keratinized
breed, white-pink color in patches, wounds and
unpigmented areas of the sores, any lesion
skin
mouth, nose, and no discharge, pink discharge, blindness,
eyes mucosa, normal dentition lesions, ulcers
for age
anus, vulva normal size, pink mucosa, diarrhea, excessive or
not fouled; vulva may purulent discharge from
show watery, clear to vulva, prolapses; red,
whitish discharge swollen vulva is a sign of
estus
feet, legs, and gait normal stance and foot lesions, swollen
movement joints, difficulty in lying
down and getting up,
lameness
respiration* no coughing or sneezing, frequent coughing or
normal respiration sneezing, forced or
superficial respiration
cardiovascular normal pulse rate collapse during restraint
system*
feces solid, brownish-yellow to watery or extremely
brownish green color, hard; reddish, black, or
depending on feed yellow color
*Auscultation in swine is difficult because of the course hair, and often because
of lack of cooperation and loud vocalization of the animal.
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microbiological sampling63,92
Blood samples for serology are taken from the jugular vein or
cranial caval vein. Usually, not more than a few drops of blood
can be taken from ear veins, but this may be sufficient for some
tests. Methods of blood sampling are described in Chapter 5.
Sterile, cotton-tipped swabs should be used for sampling
nasal secretions. The swab is introduced into one of the nares,
and inoculated onto a plate or kept in Stuart's transport medium
for bacterial culture.
A fecal sample is collected from the rectum and divided into
two parts. One part is kept in a sterile tube for microbiological
examination, while the other is used for parasitology and is kept
in a plastic container for fecal flotation.
A skin scraping for fungi and mites is taken with a sterile
scalpel blade from an area with lesions or the shoulder, and
kept in a sterile tube for microscopic inspection.
The samples are immediately sent to a health monitoring
laboratory for serological, microbiological, and parasitological
examination. Infectious agents that can be included in the exam-
ination are listed in Table 3.5.
diseases of swine
A complete overview of diseases of swine is not possible within

the scope of this book. If a detailed description of disease is
94
required, it is recommended to use Leman's Diseases of Swine
95
as a reference handbook. An atlas of swine diseases is a useful
tool in diagnosing disease. A summary of swine diseases is given
in Table 4.2.
It should be stressed that prevention of disease by procuring
swine from reliable sources is essential. Use of health-monitored
swine, preferably with an SPF or microbiologically defined sta-
tus, reduces the risk of introducing infectious disease into the
laboratory facility. Swine from sources with differing health
statuses should not be housed together. Thorough sanitation
and disinfection of animal facilities is essential for disease con-
trol. Pathogens may be harboured in the animal facility and,
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Fig. 4.1 Iron dextran (100 mg/kg IM)
Fig. 4.2 Administration of iron to neonatal swine
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consequently, nondiseased swine may be infected, even though
no swine have been present in the facility for a long period.
therapeutic treatment
Medical treatment starts early in the life of swine. All newborn

swine are treated with a prophylactic iron medication. Leaving
96
out iron treatment will lead to severe anemia. This is due to
the rapid growth rate of newborn swine and the low iron content
of sow's milk. Most common is intramuscular treatment with
97
100 mg/kg iron-dextran, but oral dosing is also applied to
prevent neonatal anemia.
Swine have often been exposed to therapeutic treatment, and
one has to consider that this may have an influence on the
experiment. Iron treatment will often lead to siderosis, with iron
97,98
deposits in the liver, kidneys and lymph nodes. But swine
are also routinely treated with antimicrobial and antihelminthic
agents, especially swine originating from agricultural sources.
This could lead to disease after experimental procedures since
infection, suppressed with antimicrobial treatment, may
progress to disease as the animal may be immunosuppressed
99
due to the experimental procedure.
A relatively small number of pharmaceutical compounds are
available for swine. Antimicrobial feed additives make up by far
the largest volume of chemotherapeutic agents administered to
swine. They are administered at low, often subtherapeutic levels,
100
for disease control and improvement of growth rate; hence,
they are often called growth promoters. Growth promotors
should not be used in purpose-bred laboratory swine, and are
not used in miniature swine at the breeding station.
Antimicrobial and antihelminthic therapy may be used in all
swine for the treatment of clinical disease. Table 4.3 lists anti-
microbial drugs for swine, along with guidelines for dosing. It
is recommended to review drug labels for specific doses.
pathological examination
Diseased swine with no prospects of natural recovery or recovery
after medical treatment must be euthanized. Methods of euthanization
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TABLE 4.2: DISEASES OF SWINE92,94
System Condition Cause Remarks

Cardiovascular Myocarditis Streptococci Increased heart rate, sudden death
Encephalomyocarditis virus
Foot-and-mouth
Swine vesicular disease
Vit. E/selinium deficiency, iron deficiency
Malignant hyperthermia
Pericarditis Pasteurella spp. Increased heart rate, sudden death
Mycoplasma spp.
Hemophilus parasuis
Actinibacillus pleuropneumoniae
Streptococci
Vasculitis African swine fever Blood loss, bleedings, anemia
Hog cholera
Erysipelas
Hemophilus parasuis
Actinibacillus pleuropneumoniae
Hemorragic Intoxication Blood loss, bleedings, anemia
conditions Factor VIII deficiency
African swine fever
Platelet disorders (thrombocytopenia)
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TABLE 4.2: DISEASES OF SWINE92,94
System Condition Cause Remarks

Digestive Enteritis Rotavirus Watery to pasty diarrhea
Coronavirus Watery diarrhea
Isospora suis (coccidiosis)
Escherichia coli
Clostridium perfringens Hemorrhagic diarrhea
Serpulina hyodysenteriae Mucohemorrhagic diarrhea
Salmonella spp.
Trichuris suis
Campylobacter spp. Variable
Respiratory Atrophic Pasteurella multocida Nasal discharge, snout deformities
rhinitis
Bordetella bronchiseptica Nasal discharge, sneeze
Mycoplasmae Nasal discharge
Pneumonia Mycoplasma hyopneumoniae Dry cough
Actinobacillus pleuropneumoniae Forced respiration, fever, dogsitting
position
Pleuritis Bordetella bronchiseptica Cough, forced respiration, fever
Viral airway Influenza H1N1 and H3N2 Dry cough, superficial respiration
infections
Aujeszki's disease Cough, periodical fever
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TABLE 4.2: DISEASES OF SWINE
System Clinical sign Cause Remarks

Skin and skeletal Lameness Osteochondrosis (genetic, Vit. D Weak legs, kneeling position
deficiency, nutrient imbalances)
Arthritis Streptococci, Mycoplasmae Swollen, hot joints
Foot lesions Housing conditions (concrete floors, Lesions on hooves, lameness
grids)
Exudative Staphylococcus hyicus Greasy pig disease, black greasy
dermatitis spots
Erysipelas Erysipelothrix rhusiopathiae Red spots, generalized
Abcesses Sterptococci, Actinomyces pyogenes, Enlargement under skin, purulent
multiple agents inflammation
Dermatitis Candida albicans Circular spots, grey exudate
Ringworm Microsporum, Trichphyton Circular red spots
Swine pox Swine poxvirus Palules and pustules
Vesicular diseases Foot-and-mouth, Swine vesicular Vesicular lesions especially on the
disease, Parvovirus snout and edge of the hooves
Parakeratosis Zinc deficiency Eryhtematous areas, overlaid with
scales
Hyperkeratinization Unknown Brownish greasy scales on the
back
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TABLE 4.3: ANTIMICROBIAL DRUGS FOR SWINE100
Drug Maximum daily dose Intervalb Routec

(mg/kg)a
Amoxicillin 11-13 SID PO
Ampicillin 20 TID SC, IM
Erythromycin 11-20 SID IM
Lincomycin 11 SID IM
Neomycin 11 SID PO
Oxytetracycline 7-11 SID IM
Oxytetracycline 44-55 SID PO
Sulfachlorpyridazyne 77-110 SID PO
Sulfamethazine 240 SID PO
Sulfathiazole 220 SID PO
Tiamulin 9 SID PO
Tylosin 18-22 BID IM
Ceftiofur 3 SID IM
Enrofloxacin 2.5 SIC IM
a) Review drug labels for specific dosages

b) SID = once a day; BID = twice a day; TID = three times a day
c) PO = oral (per os); SC = subcutaneous; IM = intramuscular
are described later in this chapter. General conditions in which euth-

anization is advised are:
rectal or vaginal prolapses with tissue damage
wounds of such severity that healing is in doubt
multiple sores and wounds, including tail-biting wounds
cardiac failure
lameness from a broken leg or arthritis
paralysis or neurological disorders
strangulated hernias
emaciation
severe septicemia, pneumonia, or enteritis
The procedure for necropsy is described in Chapter 5.
anesthesia and analgesia
Swine are considered challenging animals to work with. Lack of

cooperation when physical restraint is applied often hinders
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examination and treatment procedures in these animals. They
vocalize loudly and struggle hard when restrained. Furthermore,
massive restraint imposed on swine may profoundly stress car-
diopulmonary function. Therefore, chemical restraint or anes-
thesia are often needed for even minor procedures.
Anesthesia of swine presents some special problems com-
pared to other animal species. There are few accessible super-
ficial veins and arteries. Tracheal intubation can be difficult
because of anatomical peculiarities (i.e., small oral orifice, dorsal
protrusion of the tongue, and ventral sloping of the larynx) which
make the laryngeal opening difficult to see. Also, there is a high
incidence of malignant hyperthermia.
Reactions of Swine to Sedation and Anesthesia

During development of sedation and anesthesia, swine first
become ataxic. Soon after they lose their righting reflex and
become immobile and unresponsive to nonpainful manipula-
tions. At this stage, purposeful movement will occur in response
to a painful stimulus, and the swine may vocalize and try to
right itself. When anesthesia continues to deepen, the animal
will still make purposeful movements in response to painful
stimuli but will not vocalize or attempt to right itself. With
further deepening of anesthesia the response to painful stimu-
lation is limited to the specific region stimulated, whereas with
deep anesthesia local movement in response to a painful stim-
ulus is either slight or completely absent.
Routes of Administration of Sedatives and Anesthetics

Sedatives are usually administered by intramuscular (IM) route,
whereas anesthetics are generally administered intavenously
(IV). Routes of administration are described in Chapter 5.
Preanesthetic Management
Like all other animals, swine should be acclimatized for prefer-
ably one to two weeks in the experimental facility before being
submitted to anesthesia and surgical procedures. Clinical exam-
ination as described in Table 4.3 should be performed before
any procedure.
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The animals should not be fed 12-24 hours prior to anesthesia
to prevent vomiting during and after anesthesia. Piglets are
prone to hypoglycemia and should be held from sucking for only
1-2 hours prior to anesthetic induction. The fasting time should
only be decreased in emergency situations, as fed swine are
prone to develop gaseous distention and are at an increased
101
risk of vomiting with aspiration. Animals should not be
deprived of water at any time unless gastric surgery is being
performed, and in these cases water should only be withheld
for a few hours prior to surgery. The animals should be weighed
in order to calculate the correct anesthetic dosage.
Fig. 4.3 Drugs for premedication (azaperone 4 mg/kg, mida-

zolam 0.5 mg/kg, atropine 0.04 mg/kg IM)
Premedication
Animals are premedicated in order to sedate and relax them
before the anesthetic procedure. The premedication will also
reduce the dosage of the anesthetic drug. Often the premedica-
tion will include an analgesic drug (preemptive analgesia). In
most cases atropine should be administered to reduce bronchial
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and salivary secretions, and to protect the heart from vagal
inhibition which might occur during endotracheal intubation or
during surgical procedures, particularly if the viscera are han-
dled.
F i g . 4 . 4 IV access to the ear vein with a 22-gauge Venflon

cannula
Delivery of inhalation anesthetics via a face mask is very stress-
ful and should be avoided if possible. The induction should be
performed in quiet surroundings, as sedated animals are sus-
ceptible to noise. An IV access of the ear veins is prepared on
the dorsal surface of the ear and the skin is rinsed with alcohol.
While the vein is being compressed at the base of the ear, a 22-
gauge Venflon cannula, or similar cannule, with a length of 25
mm (1 inch) is introduced into the vein and secured with adhe-
sive tape. The Venflon cannula should be flushed with hepari-
nised saline.
Two common anesthetics for induction are:
1. Propofol (5 mg/kg IV)
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Half of the dose is given relatively rapidly, and after one
to two minutes the remaining propofol is slowly injected
until the animal is reflexless, i.e., relaxation of the jaw
muscle and total absence of muscular contractions of
the tongue. At this point the animal should still breathe
spontaneously. (The more rapidly the anesthetic is
injected into the vascular system, the more rapidly the
animal goes through the different anesthetic stages.
Passing the different anaesthetic stages should not be
too slow, but not too rapid, either.)
2. Thiopentone (6 mg/kg IV)
The same procedure is used as for propofol, but not as
rapidly. Inject half of the dose during the first minute,
and after a few minutes inject the remaining thiopentone
until the animal is reflexless.
Endotracheal Intubation
Endotracheal intubation should be performed as soon as anes-
thesia is induced. It provides a means of alveolar ventilation
and protects the airway and lungs in the event of regurgitation.
Endotracheal intubation can present some difficulties, but once
the anatomy is understood the procedure is easily carried out.
Proper placement of the tube is confirmed by feeling expired air
moving through the tube or by visual confirmation via laryn-
goscopy. The size of the tubes range from Nos. 3.0-8.0 for swine
under 50 kg, and Nos. 8.514.0 for swine over 50 kg. Once the
tube is in place, it should be secured using tape or gauze around
101
the lower jaw.
Endotracheal intubation is usually followed by apnea, so
assisted ventilation is critical at this stage, but excessive venti-
lation will decrease blood carbon-dioxide concentration and may
prolong apnea. The tube is connected to a Magill circuit with
oxygen, and the reservoir bag is depressed once or twice to
ventilate the animal manually. This should be repeated until
the animal has a regular spontaneous ventilation.
The intubation procedure may be performed with the animal
in dorsal, lateral, or sternal recumbency.
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Dorsal recumbency
The swine is placed in dorsal recumbency. No assistant is
needed. The laryngoscope is positioned with the handle turned
Fig. 4.5 Endotracheal intubation, schematic. The laryngoscope

(1) first presses the soft palate (3) to dorsal, and thereafter the
tongue to ventral, to reveal the epiglottis (2). When the laryngeal
opening is visible, a tube can be inserted. A= oropharynx; B=
nasophanynx; 1= laryngoscope; 2= epiglottis; 3= soft palate; 4=
pharyngeal diventicle; 5= laryngeal diventricle; 6= trachea; 7=
esophagus
upward and passed into the pharyngeal cavity. The tip of the
laryngoscope is used to displace the epiglottis from the soft
palate. Now the epiglottis and the laryngeal aperture are visible
and can be sprayed with a topical local anesthetic (lidocain) to
prevent laryngeal spasm and coughing when intubating lightly
anesthetized animals. The epiglottis is depressed with the tip of
the laryngoscope upwards against the base of the tongue, and
firm pressure with the blade of the laryngoscope presses the
maxilla against the surface of the table. Now the vocal cords
can be observed. The laryngoscope is tilted 45, which will result
in the larynx being flattened against the ventral surface of the
neck. As a result the laryngeal passage will be straightened. The
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endotracheal tube is passed into the trachea during expiration
while being gently rotated in a screw-like fashion. This will
facilitate the passage through the apertura without undue
102,103,104
force.
Lateral recumbency
The swine is placed in left lateral recumbency with the assistant
extending the neck by holding the upper jaw with the left hand
and the lower jaw and the tongue with the right hand. A laryn-
goscope with a 20-25 cm straight blade is placed at the base of
the tongue. With the tip of the laryngoscope, the soft palate is
lifted upwards so that the epiglottis becomes visible. The larynx
is sprayed with a topical local anesthetic. The endotracheal tube,
stiffened by a guide, is used to press the epiglottis forward onto
the base of the tongue, and the tip of the laryngoscope blade is
placed on the epiglottis to bring the vocal cords into view. The
tube is now advanced into the trachea during expiration. A slight
rotation of the tube will facilitate the introduction.
Fig. 4.6 Endotracheal intubation, lateral recumbency. The

assistant holds the mouth open
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Sternal recumbency
The swine is placed in sternal recumbency with the assistant
holding the mouth open. The procedure is the same as described
for lateral recumbency.
Fig. 4.7 Endotracheal intubation, lateral recumbency. After the

laryngeal opening is visualized with a laryngoscope, a tube is
inserted
General Anesthesia
General anesthesia can be maintained by either inhalation
anesthesia or continuous infusion.
Inhalation anesthesia
Halothane(1-2%) in an oxygen/nitrous oxide (1/1) mixture.
Isoflurane(1.5-2.5%) in an oxygen/nitrous oxide (1/1) mixture.
Sevoflurane(2.5-3.5%) in an oxygen/nitrous oxide(1/1)
mixture.
Respiration should be assisted by artificial respiration with
a tidal volume of 8-12 ml/kg body weight, and a frequency of
101
15-20 strokes per minute.
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TABLE 4.4: ANESTHETIC PROTOCOLS.
Premedication Combinations
Azaperone 4 mg/kg IM Moderate to deep sedation; no analgesia; moderate muscle

Midazolam 0.5 mg/kg IM relaxation; non-painful manipulation possible.
Atropine 0.04 mg/kg IM
Ketamine 6-10 mg/kg IM Deep sedation, or short term surgical anesthesia; muscular
Medetomidine 0.06-0.08 mg/kg IM relaxation; laryngeal relaxation makes intubation possible;
Butorphanol 0.2 mg/kg IM effectively reversed by yohimbine.110 111
Tiletamine/Zolazepam 4.4 mg/kg IM Reliable and rapid anesthetic induction, or light to medium
Xylazine 2.2-4.4 mg/kg IM short term anesthesia for minor procedures; laryngeal
relaxation makes intubation possible; apnea may occur.102
106 108 112 113
Propofol 1.55.0 mg/kg IV Rapid induction, rapid recovery; rapid injection may cause
apnea.102 104 105
Thiopental 6.6-25 mg/kg IV Dilute to 5% solution; prolonged recovery; apnea may
occur.102 104 105
Inhalation Anesthesia
Nitrous oxide MAC= 195% Low potency in swine; not as sole agent; reduces the
requirement of other inhalant agents.103 105
Halothane MAC= 0.91-1.25% Potent myocardial depressant (dose-dependant); lower
safety margin than isoflurane and sevoflurane.103 105
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TABLE 4.4: ANESTHETIC PROTOCOLS.
Isoflurane MAC= 1.2-2.04% More rapid induction and recovery than halothane; dose-
dependant depression of cardiovascular system less than
with halothane, and at higher doses; combination with
nitrous oxide reduces the dose required; no hepatic injury;
minimal biotransformation.103 105
Sevoflurane MAC= 2.3-2.66% New agent; very rapid induction and recovery; minimal
biotransformation; minimal cardiovascular depression.
Infusion Anesthesia
Propofol infusion 4-7 mg/kg/h IV Poor analgesia; must be combined with potent analgesic for
major surgical procedures.
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Infusion anesthesia
Propofol infusion: 4-7 mg/kg/hr IV, in combination with
104
a potent analgesic, e.g., fentanyl (30-100 m g/kg/hr IV).
Anesthetic Maintenance and Assessment of Anesthetic

Depth
During a specific anesthetic regimen it is important to assess the
anesthetic depth continuously. Autonomic responses have been
assumed to be of value in animals, but properly validated studies
still need to be done. In spite of this, it seems reasonable to assume
that i neuromuscular blockers are not used, the loss of conscious-
ness and unresponsiveness to painful stimuli will indicate ade-
quate anesthesia for most drugs. It is generally accepted that
purposeful movement in response to painful stimulus must be
taken as indicating conscious awareness of pain. During surgical
anesthesia the animal should not react to painful stimuli. A sur-
gical rat-tooth forceps should be used to apply the stimulus in
order to predict the absence of response to a surgical stimulus.105
Different areas of the body lose their sensitivity to noxious
stimuli at different planes of anesthesia. Loss of response in the
tail occurs first, followed by loss of pedal withdrawal, and finally
loss of response to stimulus to the nasal septum and perianal
region. Stimulus to a dew claw, applied at full pressure with a
forceps at the level of the coronary band, will be followed by
pedal withdrawal or muscle twitch when the anesthetic level is
insufficient. Stimulus to the nasal septum or the lateral lip fold,
applied at moderate pressure, will be followed by head shaking,
jaw clamping, or vocalization. Stimulus to the perianal region
(anal sphincter), also applied at moderate pressure, will be
followed by contraction of the sphincter muscle. Laxity of jaw
tone and a stable heart rate indicate that a surgical plane of
anesthesia has been achieved.102 Autonomic responses (e.g.
increase in heart rate or blood pressure of more than 10%) may
indicate inadequate anaesthetic depth.105
Drugs used in Swine Anesthesia
Anticholinergics
Atropine:
Reduces bronchial and salivary secretions
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Protects the heart from vagal inhibition, which may
occur during intubation or surgical procedures101, 103
Glycopyrrolate:
Reduces bronchialand salivary secretions
Protects the heart from vagal inhibition
Longer duration of action than atropine
Glycopyrrolate is the drug of choice in swine, since they
occasionally vomit during the recovery period. The drug
tends to decrease gastric fluid secretion and acid con-
tents, and promotes gastric emptying.103
Tranquilizers and sedatives

Phenothiazine: acepromazine
Produces sedation, but no analgesia
Acts synergistically with other anaesthetics and narcotic
analgesics, and reduces the required dosages of these
drugs
The duration of action may extend into the postoperative
phase, making recovery smooth. Moderate hypotension
may occur.108
Butyrophenones: azaperone, fluanisone
Sedation but no analgesia
More potent than phenothiazines
Some hypotension may occur101,103
Benzodiazepines: diazepam, midazolam, zolazepam

Induce mild hypnosis, sedation and muscle relaxation,
but little or no analgesia
Potentiate the action of most anesthetics and narcotic
drugs
Midazolam, being water soluble, may be more reliable in
uptake. Midazolam is more potent than diazepam and
hence requires a smaller dose, but has a shorter duration
of action.
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Antagonists exist (Flumazenil)103,108
Alpha-2-agonists: xylazine, medetomidine

Should not be used as a sole agent.
Alpha-2-agonists have transient analgesic activity and
produce hypotension.
In combination with other agents, good sedation and
muscle relaxation is provided.
Specific antagonists exist (Atipamezole, Yohim-
bine).101,102,108, 109,110
Anesthetics
Ketamine:
Produces a state of cataleptoid sedation with variable
analgesia, increased muscle tone and amnesia.
Minimal depression of the cardiovascular system.
Should not be used as a monoanesthetic since it does
not provide adequate analgesia and muscle relax-
ation.102,105, 107
Tiletamine/zolazepam:
Produces heavy sedation and immobilization for approx-
imately 20 minutes
In combination with other drugs (e.g., xylazine) endotra-
cheal intubation is possible and adequate analgesia is
provided.101, 102, 106, 107, 111,112
Barbiturates: pentobarbitone, thiopental

Dose-dependent sedation advancing into hypnosis.
Poor or no analgesic activity.
Swine are prone to apnea secondary to the administra-
tion of these drugs and assisted ventilation is necessary.
Severe cardiovascular depression and prolonged recovery
may occur.
Should not be used as a sole agent.101,102,108
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Isopropyl derivative: Propofol
Hypnotic agent providing effective sedation, muscle
relaxation, and moderate analgesia with a minimal
depression of cardiovascular function.
Rapid onset and short duration of action
Apnea may occur, so assisted ventilation must be at
hand. Must be combined with adequate analgesic for
major surgery.
No preservative is added, therefore the entire vial must
be used shortly after opening to avoid the risk of bacterial
contamination.101,102,103
Antagonists
Atipamezole:
A potent, selective, specific alpha-2-antagonist.
Effectively reverses medetomidine and xylazine sedation.
Flumazenil:
Specific benzodiazepine antagonist.
Antagonizes lingering sedation and muscle relaxation.103
Nalbuphine:
Specific opioid agonist-antagonist.
Antagonizes the effects of m-agonists (i.e., fentanyl),
while maintaining an analgesic effect at k-receptors.108
Naloxone:
Pure opioid antagonist with effect at m and k-receptors.
Yohimbine:
A specific alpha-2-antagonist.
Rapidly reverses the effects of xylazine.113
Doxapram:
Analeptic with specific stimulatory effect on the respira-
tory system.
Short duration of action, therefore repeated doses may
be required.108
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Analgesia
Pain is a severe, unpleasant sensory and emotional experience
accompanied by fear, anxiety, and panichence suffering of
the animal. Even though there is still a lack of objective means
of pain recognition and assessment in animals, it is reasonable
to assume that pain is of significance to animals and is a
sensation they would rather avoid if they could. Until we know
more about pain perception in animals, we must assume that
conditions which would cause pain in man also lead to the
perception of pain in animals thus it is appropriate to
administer analgesics to prevent pain where it is likely to
occur.103,114
Pain Control
The goal is to weaken or interrupt the nociceptive process at one
or more points between the peripheral nociceptor and the cerebral
cortex. This is done by using balanced analgesia, where analgesic
drugs are administered in combination and at multiple sites to
induce analgesia by altering more than one part of the nociceptive
process. An opioid analgesic combined with a nonsteroidal anti-
inflammatory drug (NSAID) and a local anesthetic could be used.
A local anesthetic (e.g., bupivacaine) infiltrated at the site of inci-
sion will provide analgesia for 10-12 hours, whereas a NSAID will
weaken transduction of the noxious stimuli by decreasing pro-
duction of endogenous algogenic substances (e.g., prostaglandins)
at the site of injury. Opioids will weaken the perception of pain
in the brain.
Preemptive analgesia refers to the application of balanced
analgesic techniques prior to exposing the patient to noxious
stimuli. Administration of drugs prior to a painful procedure
will provide the optimal analgesia.102
Surgically induced pain may require the use of opioids for 24-
48 hours postoperatively (72 hours after major surgery).103, 108
NSAIDs may be used in combination with opioids postoperatively
for 24-36 hours, and can be continued when opioids are no longer
necessary for a further 24-36 hours.108
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Pain Recognition in Swine
It is important that swine recover rapidly after surgical proce-
dures. Rapid recovery will without doubt influence wound heal-
ing positively.
Since there still are no objective tools for pain assessment in
swine, the animals' behavior serves as a standard for subse-
quent pain evaluation. Normal behavioral observations in swine
include interest in the surroundings, including staff; willingness
to move around; explorative behavior; tail wagging; reaction to
handling; vocalization when presented with feed; and willingness
to eat. When swine react differently from this pattern, pain and
distress might be the cause; e.g., when swine lie unresponsive
in sternal recumbancy, it is a typical indication of pain. Also,
when swine are reluctant to eat, pain or distress should always
be considered.115
Drugs Used in Swine Analgesia
Opiates
Opiates are potent analgesics with relatively short half-lives that
are used to alleviate severe and acute pain.103
Butorphanol:
Potent mixed agonist-antagonist that has three to five
times the potency of morphine.
Its m-antagonist properties can be used to reverse the
action of fentanyl while maintaining some analgesic
effects by its agonist action at k-receptors.103
Buprenorphine:
Potent partial m-agonist.
Prolonged duration of action (6-12 hours).103
Fentanyl, Sufentanil:
Potent analgesics, about 80-100 times more potent than
morphine.
Respiratory depression may occur.
Short duration of action.
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Part of balanced anesthesia during surgery; adminis-
tered as continuous IV infusions.108
Non-steroidal anti-inflammatory drugs (nsaids)

Good analgesia for post-surgical pain, or where pain is induced
by inflammation or is chronic and of integumentary or muscu-
loskeletal origin. NSAIDs should not be combined with steroids
or other NSAIDs, but can be combined with opioids or local
anesthetics. Adverse reactions such as disturbed renal function,
impaired platelet function, and gastrointestinal ulceration and
bleeding may occur.103
Carprofen:
Good analgesic for orthopedic and soft-tissue postoper-
ative pain.
Can be administered preoperatively.
No nephrotoxicity, gastro-intestinal bleeding, or hemo-
static problems.
Flunixin:
Should not be administered for longer than three days.
Ketoprofen:
postoperative and chronic treatment of pain.
Keterolac:
Should not be administered for longer than three days.
Moderate to strong analgesic properties.116
Phenylbutazone:
Mild analgesic properties.
Monitoring during Anesthesia

The cardiovascular system, the pulmonary system, and body tem-
perature are important parameters to monitor during anesthesia.
Monitored values should be recorded every ten minutes. Evalua-
tion of the cardiovascular system can be performed by palpation
of peripheral pulse, blood pressure measurement (invasive or non-
invasive), heart rate, and ECG.101 One should remember that ECG
monitoring only assesses the electrical activity of the heart and
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not the mechanical activity.102 Evaluation of the respiratory system
can be perfomed by evaluation of mucous membrane color, blood
gas analysis, pulse oximetry, capnography measures, and blood
pH.
Anesthetic Support
The swine is very prone to hypothermia because of inefficient
thermoregulatory mechanisms and very little body hair, as well
as a large body-surface area. Thermal support is therefore of vital
importance. Circulating warm-water blankets as well as blankets
during surgery will minimize the heat loss.
Intravenous fluid administration during the whole anesthetic
period with a warmed, balanced electrolyte solution administered
at a rate of 5-10 ml/kg/hour should be standard.101
Postoperative apnea is often a problem. When a swine is taken
from the respirator, the ability to breathe should be carefully
monitored.102
Anesthetic Emergencies
Laryngospasm
Insufficient anesthetic level, excessive manipulation, numerous
unsuccessful attempts to intubate, and extubation may all lead
to laryngospasm. Succinylcholine 1-2 mg/kg IV and immediate
ventilatory support may be attempted. Local spraying of the lanynx
with 2% lidocain prior to intubation will decrease the risk of
laryngospasm.101
Edema of the larynx

Difficulties in connection with intubation and overinflation of the
endotracheal cuff can cause swelling and edema of the airways,
and can lead to airway obstruction. Such tissue trauma does not
become apparent until the swine is extubated. Corticosteroids,
NSAIDs or diuretics may be given prophylactically or symptom-
atically.101
Respiratory system
Insufficient ventilation of the animal can lead to respiratory
arrest and death. Whenever there is insufficient ventilation or
respiratory arrest, the oxygen supply should be checked. Admin-
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istration of anesthetic, including nitrous oxide, should be
stopped and 100% oxygen given. Ventilation must be assisted,
manually or mechanically. The airways must be checked to see
if the tongue is obstructing the larynx. The respiratory tract
should be aspired to remove bronchial secretions, blood, or
vomit. A specific respiratory stimulative such as Doxapram can
be used in a dosage of 5-10 mg/kg IV. The action of this drug
is of relative short duration, so repeated doses may be required
every 15-20 minutes. A specific antagonist should be considered.
Cardiovascular system
Most anesthetic drugs depress the cardiovascular function. In
case of cardiovascular failure, administration of anesthetic should
be stopped and ventilation assisted with 100% oxygen, 12-20
breaths/min. Rapid intravenous infusion of fluids (isotonic saline,
plasma expanders, or whole blood) is given. Any hemorrhage is
controlled, and if bradycardia occurs, this is treated with atropine
0.02 mg/kg IV (or intratracheally). In case of cardiac arrest,
external cardiac massage, 80-100 compressions/min, should be
given. Adrenaline 0.01 mg/kg is administered intracardially, but
IV administration or administration into the endotracheal tube
can also be performed.
Malignant Hyperthermia/Porcine Stress Syndrome

Malignant hyperthermia/Porcine Stress Syndrome is a hereditary
condition where the animal, when exposed to halothane, shows
increased blood lactate concentration followed by metabolic aci-
dosis and hyperkalemia. The symptoms are tachycardia, stiffness
of the muscles, tachypnea, and hyperventilation, which rapidly
progresses to apnea, cyanosis of the skin, and a rapid rise in
body temperature. The treatment consists of IV administration
of dantrolene 1-3 mg/kg. The condition can be prevented by
injecting dantrolene 3.5-5 mg/kg IV prior to administration of
halothane.102
Postoperative Management
Postoperative care is of vital importance, and frequent monitoring
of the animal cannot be overemphasized. Recovery should always
take place in a separate room where the animal cannot injure
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itself. A room temperature of 25 C (77 F), a heating lamp, and
circulating warm-water blankets can be used to prevent hypoth-
ermia. Extubation should only be performed when a strong swal-
lowing reflex is apparent. In case of postoperative vomiting or
excessive secretions, the respiratory passages should be cleared
by suction. Fluids and antibiotics should be administered when
necessary.
euthanasia
Swine are euthanized humanely by IV injection of 20% solution
of sodium pentobarbitone, either directly into the cranial caval
vein or into an ear vein after sedation. If the use of sedatives
and anesthetics is excluded, a captive bolt can be used. This
method must be followed by exsanguination. With any method,
cessation of respiration and heartbeat, as well as loss of reflexes,
are good indicators of irreversible death. Death should always
be confirmed by exsanguination.115
Fig. 4.8 Captive bolt pistol; the bolt pisol is placed on the skull,
at the crossing of two immaginary lines from the ears to the eyes
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5
experimental techniques
Swine have been used as experimental animals throughout his-

tory, mainly in anatomical and physiological research. In his De
Humani Corporis Fabrica from 1543, Vesalius referred to swine
experiments performed by the Roman physician Galen (130-200
AD), but made observations in swine himself as well. Also,
Harvey, in his Anatomica de Motu Cordis et Sanguinis Animalibus
(1628), and Bernard, in his Introduction l'tude de la mdicine
exprimental (1865), described observations made in swine. At
present, swine are used in a wide range of disciplines.
restraint
Restraint techniques in swine fall into three categories: manual

11,12, 94
restraint, mechanical restraint and chemical restraint.
An often forgotten but simple method of restraint of placid sows
is stroking the abdomen while talking softly to the animal. This
will allow general examination. In any case, the animals have
to be approached first.
Swine have to be approached quietly, and talking softly will
calm the animal. Crouching is less threatening to the animal
than standing and bending over it. Usually, the swine will face
the approaching person in an awaiting attitude. When swine
feel threatened, they face toward the source of threat to avoid
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Fig. 5.1 Illustration of Galen from De Humani Corporis Fabrica
(1543)
being attacked from the side, since the natural offensive behav-
ior of swine is butting and biting on the shoulder and neck
region. Young swine and miniature swine may be seized by the
front leg in this situation and lifted up onto the arms. If the
animal is facing away or tries to escape, a hind leg may be
grabbed instead. The tail and ears should not be used to lift the
animal.
Larger swine should preferably be trained to walk from their
pens, and they can be driven in the right direction by walking
behind them. A board can be used to drive the animal, and can
also be used to restrain large swine against a wall.
Young swine and miniature swine under 15-20 kg (33-44 lbs)
can be lifted and manually restrained by holding them in one's
arms. One arm is held under the abdomen or hindquarters,
while the other arm supports the bow. This method is suitable
for a single IM administration in the cervical muscles or a short
examination. For examining the abdomen or feet, a swine can
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be positioned on its back in the lap of a sitting person. Alter-
natively, the animal can be held by both hind legs, head down.
When blood sampling is needed, drugs are to be administered,
or a short examination is necessary, large swine are often
restrained with a nose snare. A loop, usually a steel cable, is
placed around the upper jaw behind the tusks to hold the
animal. In large swine, this is often the only method of restraint,
other than chemical restraint. It is a stressful method, and
should be avoided in young and miniature swine.
Swine under 50 kg (110 lbs) can be restrained in dorsal recum-
122
bency in a V-shaped trough, or on the abdomen in a hammock.
Both methods are mainly used for short restraint for blood sam-
pling, but trained, conscious swine may be restrained in a ham-
mock over longer periods, e.g., for infusion studies or ECG
recording. In contrast to dogs being restrained in hammocks,
swine should hang freely without touching the floor, since they
cannot be trained to stand still. Mechanical restraint methods for
specific purposes may be developed individually, such as restraint
123
in a bucket for intranasal inoculation or swabbing.
Fig. 5.2 Restraint method using a V-trough
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Fig. 5.3 Swine restrained in hammocks during a 6-hour infu-
sion study (Photo courtesy of Scantox)
Inactivation of swine by sedatives is referred to as chemical

restraint. The most common sedative in swine is azaperone
(Stresnil, Sedaperone), which should be dosed at 4 mg/kg IM
(see Table 4.4). A single IM administration in large swine can be
carried out in the animal's pen by using a syringe with an
extension tube. The hypodermic needle is darted into the cervical
muscles and the syringe emptied. The extension tube allows
some degree of movement of the animal.
sampling techniques
Blood Sampling
There are few percutaneous access sites to veins in swine, since
veins and arteries lie either under thick skin and subcutaneous
101,103
fat, or deep between muscles. Possible sampling sites are:
cranial caval vein
jugular vein
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femoral vein
saphenous vein
cephalic vein
carotid artery
femoral artery
cardiac puncture
The cranial caval vein and femoral vein are most often used,
and the procedure will be described. The ear veins are not suited
for withdrawal of large blood samples since these veins are too
small and will collapse upon withdrawal of blood. Arteries should
be avoided for blood sampling since puncture may lead to the
formation of hematoma.
The best location for blood sampling is from the cranial caval
vein, with the swine in dorsal recumbency. Large swine have to
be restrained standing, with a snare. For dorsal recumbency,
the swine may be placed on a table top or in a V-shaped trough,
the latter being preferable as it limits the movements of the
animal. One or two assistants are required to restrain the animal
in addition to the person taking the blood sample. The front legs
are bent caudally and the neck is stretched, holding the animal
by its snout. A second person may hold the hind legs. To prevent
a rightening reflex when placing the animal on its back, the
animal should not be rolled over the longitudal axis into the V-
shaped trough, but over the transversal axis. When this is done
in a quiet manner the animal will be relaxed and easy to restrain.
The manubrium of the sternum is now palpated, and a 21-gauge
hypodermic needle inserted into the medial plane at an angle
of 45-60 to an imaginary horizontal line, a few millimeters
cranial to the manubrium of the sternum. Creating a slight
vacuum in the syringe while inserting the needle will facilitate
easy detection when a vein is punctured since blood will stream
into the syringe. A vacutainer blood-sampling system will ease
the procedure. For swine up to 10-15 kg (22-33 lbs), a hypo-
dermic needle of 25 mm (1 inch) can be used. Larger swine,
6
from 15-50 kg (33-110 lbs), require a needle of 45 mm (1 /8
inches), whereas swine over 50 kg (110 lbs) require a needle
1
size of 18 gauge/65 mm (2 /2 inches). The hypodermic needle
should not be inserted at too flat an angle, i.e., under 45,
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because of the risk of puncturing the pericardium or the heart.
Alternatively, a hypodermic needle can be inserted into the
jugular furrow. The point of the needle should be directed toward
the medial plane, dorsal to the manubrium of the sternum. The
angle to an imaginary horizontal line should be 45. The two
methods described will puncture the brachiocephalic plexus,
cranial to the cranial caval vein. The caval vein may also be
punctured since it is unsure exactly which vessel has been
punctured. When inserting a needle into the jugular furrow in
the sagittal plane, the jugular vein will be punctured. However,
in young swine and miniature swine, this method is not as
successful as puncturing the brachiocephalic plexus.
Fig. 5.4 Sites for blood sampling. The needle should be inserted
under 45-60, cranial to the sternum (A), or in the jugular furrow
(B), and directed toward the medial plane. To the right, the figure
shows the location og the needle in a large swine, restrained
with a snare. A= insertion point cranial of the manubrium of
the sternum; B= jugular furrow; 1= briachiocephalic vein; 2=
external jugular vein; 3= internal jugular vein
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Fig. 5.5 Blood sampling from the brachiocephalic plexus in a
miniature swine in dorsal recumbancy
The blood volume of a single sample should not exeed 10% of

124
the total blood volume. Since swine have a blood volume of
75 ml/kg, a maximum volume of 7.5 ml/kg can be taken. An
interval of 2 weeks between single samples should be respected.
In repeated sampling, as used in pharmacokinetic studies, it is
recommended to not take more than a total volume of 7.5 ml/kg.
For a 10-kg swine this corresponds to 15 samples of 5 ml within
24 hours, whereafter the animal is not sampled for two weeks.
Unlimited access to drinking water should be secured to allow
the animal to rehydrate itself. The site of sampling should be
varied in repeated sampling to reduce the risk of hematoma. For
accessing the brachiocephalic plexus, sampling could be varied
between the right and left jugular fossa and the medial plane.
If repeated sampling is necessary over a long period, vascular
101,125,126
catheterization may be considered. Methods are
described later in this chapter.
Urine and Feces
Only in sows can the urethra be catheterized since boars have
a cork-screwed penis tip and a sigmoid curve in the body of the
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penis. However, urine sampling in swine by catheterization of
the urethra is seldom performed since it requires an anesthe-
tized animal. A large suburethral diverticulum disables cathe-
terization in conscious swine since catheterization is difficult
without the help of a speculum.
Urine and feces are often collected by means of a metabolic
cage. Cages designed for dogs may be used for small or miniature
swine. Feces will stay behind on the grid floor of the metabolic
cage, while urine is collected via a pan with a funnel. Contam-
ination of urine with feces is unavoidable, but can be minimized
by collecting the feces regularly.
Cerebrospinal Fluid
Cerebrospinal fluid can be collected from the anesthetized swine
by puncturing the cisterna magna. Sampling cerebrospinal fluid
in conscious swine is not possible because of the non-coopera-
tive behavior of swine. The swine should be placed in lateral
recumbency and the head fully flexed. The cervical area should
be clipped and disinfected, e.g., with 1% chlorhexidine in 70%
ethanol. A 20-gauge spinal needle with a length of 90 mm (3
1/2 inches) provided with a stylet should be inserted about 5
cm (2 inches) caudal to the occipital protuberance and advanced
slowly toward the mouth. The needle should be kept parallel to
the table surface. The atlanto-occipital membrane and dura
mater of the cisterna magna lie about 7 cm (2 6/8 inches) deep
in a 40-kg (88 lbs) swine. A volume of 5-10 ml can be collected
at intervals of four days.127
Bile and Pancreatic Excretions

Bile and pancreatic excretions can be collected in a chronically
catheterized animal.101,128 Methods are described later in this
chapter.
administration of compounds
Small needle sizes (19-21 gauge) can be used for most swine for
SC, IM, or IV injections.104
Subcutaneous administration (SC) is not easily executed
since the swine is a fixed-skin animal, like humans. Small
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Fig. 5.6 SC administration
volumes may be given on the lateral side of the neck immediately

caudal to the ear or in the flank.104,105 In fat swine, the injection
is often administered into the subcutaneous fat.
Intramuscular administration (IM) is preferably given in the
cervical muscle groups, in the region overlaid by the ear, close
to the transition from hairy to hairless skin. This region has the
thinnest layer of fat, with the muscles closest to the skin. The
semimembranous, semitendinosus, and gluteal muscles in the
hind leg may also be used, but cause more resentment to
injection than the neck region. The drugs are administered
through a 19- to 21-gauge needle, with a minimum length of 3-
4 cm (1 1/8 - 1 6/8 inches) to ensure that the injection is given
into the muscle. The needle can be connected to an extension
tube, which will allow the swine to move freely while the drug
is being injected.
Intravenous administration (IV) often requires a sedated
animal. The central or ventrolateral ear veins are most com-
monly used. The artery is located on the dorsolateral aspect of
the ear.105 A 20- to 22-gauge hypodermic needle can be used.
The use of a butterfly needle has the advantage that the needle
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Fig. 5.7 IM administration in the neck
Fig. 5.8 IM administration in the hind leg
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Fig. 5.9 IV administration; puncture of marginal ear vein with
a butterfly needle
can be taped to the ear. When a Venflon over-the-needle can-

nula or similar cannula is used, the cannula can be kept in the
ear vein for two to three days. The use of a stylet will prevent
coagulation inside the cannula in this situation. For an emer-
gency situation the cranial caval vein can be used. This vein
can be accessed as described earlier.
Intraperitoneal administration (IP) is seldom used in swine.
basic surgical procedures101, 103
All surgery should be performed using aseptic procedures and

techniques. Anything that comes into contact with the surgical
site should be sterile, i.e., instruments, suture materials,
syringes, and needles. To prepare the animal for surgery the
hair should be removed from the surgical site with a clipper,
and the skin scrubbed with soap and water, then disinfected
with alcohol and an iodine solution. The surgical site should be
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Fig. 5.10 IV administration; administration of a compound.
The butterfly needle is kept in place with adhesive tape
isolated with sterile drapes. The surgeon and assisting staff

should wear caps, face masks, sterile gowns, and sterile surgical
gloves.
catheterization
Carotid artery and the internal jugular vein
A 5-cm (2-inch) longitudinal incision is made in the midline
approximately 3 cm (1 1/8 inches) cranial to the manubrium
of the sternum. A longitudinal incision is made in the sterno-
hyoideus muscle down to the trachea. The vessels are located
on either side of the trachea. The carotid artery and the jugular
vein are isolated for a length of 2 cm (6/8 inch) using blunt
dissection. There should be as little manipulation of the vein as
possible since it contracts easily, which makes catheterization
more difficult. After isolation of the vessel, a length of suture
material is placed around the vessel at the distal end and at
the proximal end. The distal suture is tied. The proximal suture
is placed loosely around the vessel.
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Carotid artery
An arterial clamp is positioned on the artery right after the
proximal suture. A small cut approximately 1/3 of the diameter
of the arterial wall is made with a pair of fine scissors (preferably
microscissors) close to the distal ligature. A catheter is placed
in the artery, using a vascular guide to hold the lumen of the
artery open and while the arterial clamp is slowly loosened, the
catheter is introduced into the artery. The proximal suture is
tied around the catheter and the artery, and the catheter is fixed
using the distal ligature ends.
Internal jugular vein

A catheter is placed in the vein in the same manner as in the
artery, except that it is not necessary to use the clamp. The
proximal suture is lifted slightly to empty the vessel, and the
catheter is introduced into the vein using a vascular guide. It
might be helpful to loosen the proximal suture a little just prior
to entering the vascular lumen in order to fill the vessel with
blood.
External jugular vein

A 5-cm (2-inch) longitudinal incision is made approximately 5
cm lateral to the midline in the same area as for the carotid
artery. The vein is located deep between the brachiocephalic and
the sternocephalic (sternomastoideus) muscles. The vein is can-
nulated in the same manner as described for the internal jugular
vein.
Cephalic vein
The cephalic vein joins the external jugular vein and lies super-
ficially in the axillary furrow. A 3-cm (11/8-inch) incision is
made in the furrow perpendicular to the midline and beginning
4 cm (16/8 inches) from the manubrium of the sternum. The
vessel is dissected bluntly for a length of 2 cm (6/8 inch). It is
cannulated in the same manner as above.
Femoral artery and vein

The femoral canal can be located by palpating the pulse in the
fold between sartoric and gracilic muscles. An incision is made
starting cranial to the origin of the pectineal muscle and extend-
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Fig. 5.11 IV Catheterization of the jugular vein; isolation of the
vein
ing along the femoral canal distally on the leg. The subcutaneous
tissue is dissected and the two muscle groups are located and
separated bluntly. The two vessels are located in the deep, right
next to the saphenus nerve, which lies cranial to the artery. The
vessels are carefully separated from the nerve and then dissected
over 2-3 cm (6/8 - 1 1/8 inches). Beware of the side-branches
of both the artery and the vein. These must be carefully ligated
and transsected. Both vessels are cannulated as described above.
Other vessels, such as the subcutaneous mammary veins and
the median coccygeal artery, are also suitable for cannulation.
Catheter Maintenance
Catheters need to be flushed daily using heparinized saline (2
U/mL). If an animal is receiving a continuous IV infusion, flush-
ing is not necessary during the infusion period. The end of the
injection cap should be cleaned with isopropyl alcohol before
each use to decrease the risk of introducing bacteria into the
catheter site. The catheter exteriorization site should be cleaned
daily with an antibacterial solution or ointment.
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Fig. 5.12 IV Catheterization of the jugular vein; introduction
of the catheter
Laparotomy
A 15-cm (6-inch) long midline incision is made from the xiphoid-
eal proceeding of the sternum through the skin, subcutaneous
layer, and muscle layer in the linea alba. The peritoneum is
grasped with a tissue forceps, lifted, and incised with a small
hole using a scalpel. The blunt tip of a pair of scissors is inserted
and the peritoneum is incised, lifting the tissue to make sure
not to incise the underlying organs.
Portal vein cannulation

The spleen is exposed and the gastrolienalic veins are located
between the large curve of the stomach and the spleen. The vein
is dissected carefully, without traumatizing the spleen tissue.
Two sutures are placed around the vessel. The distal suture is
tied. A small cut is made in the vein and a soft silicone tube is
placed in the vein and secured very loosely with the proximal
suture. Too tight a ligature will prevent the further insertion of
the catheter. The tube is carefully directed into the splenic vein
(sharp bend), and introduced 30-35 cm (12-14 inches) further
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until it can be palpated in the portal vein. The catheter has a
tendency to turn downward into the gastroduodenal vein. To
prevent this, the tube should be palpated by putting ones fingers
into the epiploic foramen and behind thd tube. Here, one should
be able to guide the tube gently in the cranial direction.
The hepatic vein

The left lobe of the liver is identified. An intestinal clamp is put
on the lobe to control bleeding, and a transverse incision is
made a few centimeters from the edge. A central vein is identi-
fied, and a silicone rubber tube is introduced approximately 8
cm (3 1/8 inches) into the liver after removal of the clamp. The
wound is closed by putting a hemostatic material into the wound
to control bleeding, and then suturing the wound.
Pancreatic duct
The pancreatic duct is identified near the proximal end of the
pancreas, close to the duodenum. The peritoneum is transsected
and the duct is dissected. Two ligatures are placed, and the one
next to the duodenum is ligated. The duct is cut with micro
scissors and the catheter introduced using a vascular guide.
Safety Testing of Chemicals and Drugs

Miniature swine are increasingly used as the nonrodent species
in safety testing of chemicals and drugs. Large swine are used
to a lesser extent, with the exception of toxicity testing of agro-
chemicals or other compounds available in large quantities,
since body weight, and thus dosing, of large swine are the
limiting factors. Miniature swine are used in all fields of safety
testing, including dermal toxicology,129,130 and acute and chronic
systemic toxicology by oral dosing or continuous infusion.76 131
Miniature swine have also been used in specialized fields such
as immunotoxicology,74 reproductive toxicology,132 and teratol-
ogy.133
Dermal toxicology
The procedures for acute dermal toxicity and acute dermal
irritation are described in OECD Guidelines 402 and 404,
respectively, issued by the Organization for Economic Cooper-
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ation and Development (OECD).134,135 The animals should be
prepared as follows:
The back and sides of the swine are clipped one day in
advance.
The back is divided into 6 or 8 squares on both sides of
the spine. The total surface of the squares should cor-
respond to 10% of the total body surface.
The total body surface can be estimated using:
BS = (70 x BW0.75)/1000,
where BS = body surface (m2) and BW = body weight (kg).
The equation is based on the fact that animals have a basal
metabolism of 70 kcal/kg and a heat production of 1000
kcal/m2. The use of metabolic body weight (BW0.75) makes the
equation applicable for interspecies comparison.
A prescribed amount of test compound is applied to the
skin so that all squares are covered, and dressed with
gauze pads. The pads are kept in place with adhesive
tape.
The duration of exposure should be in accordance with
the relevant regulatory guideline. After the period of
exposure, the pads are removed and the compound is
washed off the skin. The skin is then examined for
erythema and edema.130
Acute and chronic systemic toxicology

Guidelines for acute and chronic systemic toxicology relevant
for swine are, among others, described by OECD in guidelines
401, 409 and 452. Guideline 409, subchronic oral toxicity,
nonrodent: 90 days, mentions miniature swine explicitly as an
acceptable species.136
Oral administration of the test compound can be done by:
Mixing the compound directly into the feed.
Administering the compound in capsules into the
oropharynx via a balling gun.
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Administering the compound directly into the stomach
via gastric intubation.
Gastric intubation is the most controlled method of oral admin-

istration. Although swine are ready eaters, feed may have a
reduced palatability after compound has been mixed into it.
Capsule dosing has the uncertainty of capsules not being swal-
lowed. Swine have to be restrained for gastric intubation. The
procedure is as follows:
A technician sitting on a table top holds the swine in an
upright position sitting on its hindquarters; the swine is
held between the legs of the technician by firm pressure.
The front legs of the swine are bent caudally and held
with one hand. The other hand stretches the neck of the
swine, and the animal is pressed against the chest of
the technician. A seat fixed to the table top in which the
swine can sit will ease the restraint.
A soft gastric tube of 3-4 mm in diameter can be used
for miniature swine of 5-15 kg (11-33 lbs). For larger
swine, a 6 mm gastric tube can be used. The length of
the tube should reach from the mouth to past the last
rib of the restrained animal.
The tube is inserted into the mouth and introduced.
Normally, the swine will protest and vocalize loudly.
When the swine stops vocalizing, it should be checked
if the trachea has been intubated instead of the esoph-
agus by listening to the respiration. The compound is
injected into the stomach when the tube is in place. No
guidelines for maximum volumes are available, but a
typical volume is 10-20 ml.
Intravenous administration of test compound can be by single

injection, repeated administration, or continuous infusion.
Methods of single IV administration were described in earlier.
Repeated administration and continuous infusion require a sur-
gically prepared animal. Methods for catheter implantation were
also described earlier. A vascular access port can be used for
repeated administration as well as for blood sampling.125,137 For
continuous infusion, the catheter should be connected to an
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Fig. 5.13 Oral administration by gastric intubation (gavaging)
ambulatory infusion pump which is placed in the pocket of a

jacket on the back of the swine. The procedure is as follows:
After the animal has been catheterized, the catheter is
connected to the infusion pump. The catheter should be
exteriorized on the shoulder, at the same level as where
the pocket of the jacket will be located. The reservoir of
the infusion pump should be filled with saline.
A well-fitting jacket is put on the swine while it is still

anesthetized. The infusion pump is placed in a pocket
of the jacket, and a counterweight is placed into the
other pocket to balance the jacket.
When the swine wakes from the anesthesia with the

jacket in place, it will easily accept the jacket.
The battery and reservoir should be changed daily. Seven

days postoperatively the study can commence, and the
saline is replaced with test compound.
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A typical repeated dose study lasts for 28 days, whereas sub-
chronic toxicity studies last for 90 days.
Fig. 5.14 Miniature swine with jacket for continuous infusion

(Photo courtesy of Scantox)
necropsy92 ,93
Necropsy is an important tool in the diagnosis of disease, but

also in evaluating the pathological effects of an experimental
procedure. Necropsy is an essential part in the safety testing of
chemicals and drugs. Whereas for the diagnosis of disease only
affected organs are sampled for histopathological examination,
in safety testing a narrowly described list of organs is weighed
and sampled. Organs which have to be examined are described
by regulatory bodies such as the Organization for Economic Co-
operation and Development (OECD) and the Food and Drug
Administration (FDA). Table 5.1 gives an overview of organs to
be sampled for histopathological examination.
Equipment.
Necessary equipment includes rubber gloves and boots, a knife
with a five to seven inch blade, scalpel blades and holder,
scissors, and forceps. To collect tissues and take samples for
microbiological examination, containers with formalin, plastic
bags, strings, and culture swabs are essential. Helpful equipment
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TABLE 5.1: ORGANS TO BE SAMPLED FOR HISTOPATHOLOGICAL
EXAMINATION IN SAFETY TESTING OF CHEMICALS AND
DRUGS.
Organ/tissue FDA Redbooka OECDb

Adrenals left + right left + right
Aorta microscopy microscopy
Bone marrow microscopy microscopy
Brain three specified three specified sections
sections
Bronchi microscopy -
Cecum microscopy microscopy
Colon microscopy microscopy
Duodenum microscopy microscopy
Esophagus microscopy microscopy
Eyes left + right left + right
Femur - if signs of toxicity are present
Gall bladder microscopy microscopy
Heart microscopy microscopy
Ileum microscopy microscopy
Jejunum microscopy microscopy
Kidneys left + right left + right
Liver microscopy microscopy
Lungs microscopy microscopy
Lymph nodes only one node only one node
Mammary gland only one gland only one gland
Ovaries left + right left + right, including cervix
Pancreas microscopy microscopy
Pituitary microscopy microscopy
Prostate microscopy -
Rectum microscopy microscopy
Salivary glands left left + right
Sciatic nerves left left
Skeletal muscle left left
Skin - if signs of toxicity are present
Spinal cord two specified three specified sections
sections
Spleen microscopy microscopy
Stomach microscopy microscopy
Testes left + right left + right
Thymus microscopy microscopy
Thyroid including including parathyroids
parathyroids
Trachea microscopy microscopy
Urinary bladder microscopy microscopy
Uterus microscopy microscopy
a) Food and Drug Administration, Redbook, 1982.

b) Organization for Economic Co-operation and Development, Guidelines for
testing of chemicals, Section 4: Health Effects, 1981.
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includes knife, rib cutters, microscope slides, labels, ruler,
syringes, and hypodermic needles.
Preservation.
The only necessary preservative is a buffered 4% formaldehyde
solution (formalin). This can be prepared by adding 100 ml 40%
formaldehyde to 900 ml water, and adding 6.5 g diphasic anhy-
drous sodium phosphate and 4.0 g monobasic sodium phos-
phate. Specimens should not be thicker than 5 mm to allow
proper preservation. The correct tissue-formalin ratio is 1:10.
Specimens meant for microbiology should be kept in a plastic
bag in a refrigerator; they should not be kept in formalin or
frozen.
Procedure
Start by examining the external features, such as described for
a clinical examination. If the animal is found dead, and the
cornea is cloudy and the abdomen discolored green, a necropsy
is often less valuable since the animal has undergone autolysis.
The swine is placed in left lateral recumbency, then:
Cut deep into the right axilla; extend the incision to the
point of the mandible and to the anus (insert the knife
into the subcutis and cut outward); reflect the skin; cut
the right hip joint; open the stifle and reflect the limb;
examine inguinal lymph nodes.
Open the abdomen with a paracostal cut; extend to the
pelvis with a paralumbar cut; reflect abdominal wall
ventrally.
Stab diaphragm and incise; cut ribs and remove.
Examine peritoneal and thoracic cavities; if exudates,
adhesions, fibrin, or other pathological changes are
present, collect tissue for culture and histopathology;
blood and urine should be collected at this point.
Open the pericardium in situ, and examine.
Cut close to the bone on the medial side of both mandi-
bles, and free the tongue; pull the tongue caudally; cut
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hyoid bones; cut soft tissue along vertebrae and free
cervical and thoracic viscera intact.
Examine oral cavity; examine regional lymph nodes;
incise tongue, and open the esophagus.
Palpate lungs; open trachea and major airways; cut bron-
chial lymph nodes; open heart.
Squeeze gallbladder to test patency.
Compress feces from rectum; place a ligature and cut
distal from the ligature; free entire intestinal tract using
blunt and sharp dissection.
Remove both adrenals and incise with scalpel.
Remove the kidneys by pulling the ureter caudally; peel
capsules; cut to the pelvis and examine; open the urinary
bladder.
Examine and remove the reproductive tract.
Remove the spleen from the stomach and incise.
Remove skin and muscle from the head; flex the head
to locate the atlanto-occipital joint and cut to the ventral
surface of the joint; collect cerebrospinal fluid if neces-
sary; cut the joint and neck muscles, and remove the
head.
Remove the skull cap and isolate the brain; examine the
meninges; collect tissue for culture and histopathology.
Spread intestines, and open stomach, duodenum, sec-
tions of the jejunum, ileum, cecum, ascending colon and
descending colon; collect tissue if necessary*.
* Usually, the gastrointestinal tract is examined last in necrop-

sies. If the clinical problem is related to the GI tract, it should
be examined as early as possible since it rapidly undergoes
autolysis.
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6
resources
This chapter is meant to give an overview of laboratory swine-
related resources without the aim of being exhaustive. It should
be realized that resources are time sensitive, especially Internet
resources.
associations
The Association for Assessment and Accreditation of Laboratory
Animal Care International supports the use of animals to advance
medicine and science when there are no nonanimal alternatives,
and when it is done in an ethical and humane way. When animals
are used, AAALAC works with institutions and researchers to
serve as a bridge between progress and animal well-being. This
is done through a voluntary accreditation program in which
research institutions demonstrate that they are not only meeting
the minimums required by regulations, but are going the extra
step to achieve and showcase excellence in animal care and use.
11300 Rockville Pike, Suite 1211, Rockville, MD 20852-3035
Phone: 301.231.5353 - Fax: 301.231.8282
E-Mail: accredit@aaalac.org - Internet: http://www.aaa-
lac.org
1999 CRC Press LLC

AALAS
The American Association for Laboratory Animal Science is a
forum for the exchange of information and expertise in the care
and use of laboratory animals. Since 1950, AALAS has been
dedicated to the humane care and treatment of laboratory ani-
mals, and to the quality research that leads to scientific gains
that benefit mankind and animals. AALAS has more than 8500
members, including clinical veterinarians, technicians, technol-
ogists, educators, researchers, administrators, animal produc-
ers, and national and international experts.
American Association for Laboratory Animal Science
9190 Crestwyn Hill Drive, Memphis, Tennessee 38125
Phone: 901-754-8620 Fax: 901-753-0046
E-mail: info@aalas.org Internet: http://www.aalas.org
AASP
The American Association of Swine Practitioners is a nonprofit,
educational, professional society organized to increase the
knowledge of veterinarians in the field of swine medicine; elevate
the standards of swine practice; promote the relationship
between swine practice, the swine industry, and the public
interest; promote the interests of swine veterinarians; improve
the public stature of swine veterinarians; cooperate with veter-
inary and agricultural organizations and regulatory agencies;
and promote goodwill among AASP members. AASP has approx-
imately 2000 members hailing from practice, industry, and aca-
demia.
American Association of Swine Practitioners
902 1st St, Perry, Iowa 50220-1703
Phone: 515-465-5255 fax: 515-465-3832
E-mail: aasp@aasp.org Internet: http://www.aasp.org
ACLAM
The American College of Laboratory Animal Medicine is an orga-
nization of board-certified veterinary medical specialists who are
experts in the humane, proper, and safe care and use of labo-
ratory animals. ACLAM establishes the standards of education,
training, experience, and expertise necessary to become quali-
fied as a specialist, and recognizes that achievement through
board certification. ACLAM actively promotes the advancement
1999 CRC Press LLC

of knowledge in this field through professional continuing edu-
cation activities, the development of educational materials, and
the conduct of research in laboratory animal medicine and
science. ACLAM fosters the recognition of its members who
contribute to human and animal health improvements by being
the leaders of the veterinary medical specialty known as labo-
ratory animal medicine.
The American College of Laboratory Animal Medicine does not
have a permanent office address, but can be contacted through
its president or secretary. Internet: http://www.aclam.org
ASLAP
The American Society of Laboratory Animal Practitioners pro-
motes the acquisition and dissemination of knowledge, ideas,
and information among veterinarians and veterinary students
with an interest in laboratory animal practice. The society does
so for the benefit of laboratory animals, other animals, and
society in general. ASLAP believes that laboratory animals do
not differ from other animals in their need for proper preventive
and therapeutic medical care, nutrition, physical and psycho-
logical comfort, and all other elements that contribute to their
health and well-being.
The American Society of Laboratory Animal Practitioners does
not have a permanent office address, but can be contacted
through its president or secretary on the Internet:
http://www.aslap.org
FELASA
The Federation of European Laboratory Animal Science Associ-
ations was founded in 1978. Its members are the European
national laboratory animal science associations from England
(LASA), Scandinavia (Scand-LAS), Germany (GV-Solas), France
(SFEA), Spain (SECAL), Italy (CISAL), the Netherlands (NVP),
Belgium (BCLAS), and Switzerland (SGV). As an international
body, FELASA represents the common interests of the constit-
uent associations by coordinating the development of education,
animal welfare, health monitoring, and other aspects of labora-
tory animal science. Within the Council of Europe and the
European Union, FELASA has a political role through offering
authorative advice to these bodies.
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The Federation of European Laboratory Animal Science Asso-
ciations does not have a permanent office address, but can be
contacted through its president or secretary at the following
Internet address:
http://www.felasa.org
ICLAS
The International Council for Laboratory Animal Science was
founded in 1956. Its aim is to promote and coordinate the devel-
opment of laboratory animal science throughout the world, and
promote international collaboration. One of its main activities is
the harmonization of health monitoring programs, and to realize
this it has established reference health monitoring laboratories.
The International Council for Laboratory Animal Science does
not have a permanent office address, but can be contacted
through its president or secretary at the following Internet
address:
http://www.iclas.org
ILAR
The Institute for Laboratory Animal Research is a division of the
Commission on Life Sciences, one of eight major units within
the National Research Council. The National Research Council
is the working arm of the National Academy of Sciences, a
private, nongovernmental, nonprofit organization chartered by
Congress in 1863 to "investigate, examine, experiment, and
report upon any subject of science." ILAR works under the
direction of a 15-member council composed of experts in labo-
ratory animal medicine, zoology, genetics, medicine, ethics, and
related biomedical sciences. The council provides advice on all
aspects of ILAR's program, and formulates plans for the initia-
tion of new programs.
Institute for Laboratory Animal Research
2101 Constitution Avenue, NW, Washington, DC 20418
Phone: 202-334-2590 - Fax: 202-334-1687
E-mail: ILAR@nas.edu .Internet:
http://www4.nas.edu/cls/ilarhome.nsf
1999 CRC Press LLC

National SPF Swine Accrediting Agency
The National SPF Swine Accrediting Agency, Inc., dates back to
May 1952. Its aim is to maintain and monitor hysterectomy-
derived SPF swine colonies of accredited swine producers, to
eliminate and prevent chronic growth retarding diseases, and
to enlarge the economic profit of swine producers. The National
SPF Swine Accrediting Agency can be contacted to obtain
adresses of accredited swine producers in order to procure SPF
swine for the laboratory.
National SPF Swine Accrediting Agency, Inc.
PO Box 280, Conrad, Iowa 50621
Phone: 515-366-2124 - Fax: 515-366-2232
E-mail: spf@marshallnet.com - Internet: http://www.national-
spf.com
books
A wide range of reference books on laboratory swine is available.

Two general books are:
1. Mount, L.E. and D.L. Ingram, The Pig as a Laboratory
Animal, Academic Press, London, 1971.
2. Pond, W.G. and K. Houpt, Biology of the Pig, Comstock
Publishing Associates, Ithaca, NY, 1978.
The symposium "Swine in Biomedical Research" has been orga-

nized three times during the last 35 years, after which the
proceedings were published as handbooks:
1. Bustad, L.K., R.O. McClellan, and M.P. Burns, Eds.,
Swine in Biomedical research, Frayn & McClellan, Seat-
tle, 1966.
2. Tumbleson, M.E., Ed., Swine in Biomedical Research, vol.
1-3, Plenum Press, New York, 1986.
3. Tumbleson, M.E. and L.B. Schook, Eds., Advances in
Swine in Biomedical Research, vol. 1-2, Plenum Press,
New York, 1996.
1999 CRC Press LLC

One author, Michael Swindle, has published several handbooks
on laboratory swine, anesthesia and surgery, and animal mod-
els:
1. Swindle, M.M., Basic Surgical Exercises Using Swine,
Praeger Press, Philalelphia, 1983.
2. Swindle, M.M., Swine as Models in Biomedical Research,
Iowa State University Press, Ames, 1992.
3. Swindle, M.M., Surgery, Anesthesia, and Experimental
Techniques in Swine, Iowa State University Press, Ames,
1998.
A book on cardiovascular research using swine has been

published. According to the authors, this book was especially
prepared because "information on cardiovascular studies in
swine is scattered widely throughout biomedical and agricul-
tural literature, and few comprehensive reviews have been pre-
pared":
Stanton, H.C. and H.J. Mersmann, Eds., Swine in Car-

diovascular Research, vol. 1-2, CRC Press, Boca Raton,
1986.
journals
Contemporary Topics in Laboratory Animal Science

Contemporary Topics in Laboratory Animal Science is a bimonthly
publication that serves as the official communication vehicle for
the American Association for Laboratory Animal Science
(AALAS). Contemporary Topics includes a section of refereed
articles on clinical, technical, management, and philosophical
topics. CT also highlights AALAS news, upcoming meetings, and
activities. It also provides updates on other issues related to
laboratory animal science.
Phone: 901-754-8620 Fax: 901-753-0046
Internet: http://www.aalas.org/pubs/ctonline.htm
1999 CRC Press LLC

ILAR Journal
ILAR Journal is the quarterly, peer-reviewed publication of the
Institute for Laboratory Animal Research (ILAR), which is a unit
of the National Research Council, National Academy of Sciences.
ILAR Journal provides thoughtful and timely information for all
those who use, care for, and oversee the use of laboratory
animals. The audience of ILAR Journal includes investigators in
biomedical and related research, institutional officials for
research, veterinarians, and members of animal care and use
committees.
Institute for Laboratory Animal Research
2101 Constitution Avenue, NW, Washington, DC 20418
Phone: 202-334-2590 - Fax: 202-334-1687
Internet: http://www4.nas.edu/cls/ijhome.nsf
Lab Animal
Lab Animal is a peer-reviewed journal for professionals in animal
research, emphasizing proper management and care. Editorial
features include: new animal models of disease, breeds and
breeding practices, lab animal care and nutrition, new research
techniques, personnel and facility management, facility design,
new lab equipment, education and training, diagnostic activities,
clinical chemistry, toxicology, genetics, and embryology as they
relate to laboratory animal science.
Lab Animal
PO Box 5054, Brentwood, TN 37024-5054
Phone: 800-524-0384 or 615-377-3322 - Fax: 212-696-9591
Internet: http://www.labanimal.com
Laboratory Animals
Laboratory Animals is an international journal with a strong
base in Europe, but with subscriptions in 49 countries. In 1997,
papers from 19 countries were published in the journal. The
editorial board includes members from Europe and North Amer-
ica. Laboratory Animals is published by Laboratory Animals,
Ltd., and is the official journal of the Federation of European
Laboratory Animal Science Associations (FELASA).
1999 CRC Press LLC

The Royal Society of Medicine Press, Ltd.
1 Wimpole Street, London, W1M 8AE, United Kingdom
Phone: (+44) 171-290-2927 - Fax: (+44) 171-290-2929
Internet: http://www.rsmpress.co.uk/
Laboratory Animal Science

Laboratory Animal Science, an international journal of compar-
ative and experimental medicine, is the leading English-lan-
guage publication in the field. It is ranked by the Science
Citation Index in the upper third of all scientific journals. LAS
is published six times a year and presents refereed manuscripts
on topics such as diseases of laboratory animals, animal models
of human diseases, and research methodology. Laboratory Ani-
mal Science serves as a forum for the exchange of information
on etiopathogenesis, epidemiology, diagnosis, therapy, and pre-
vention of infectious and noninfectious diseases of laboratory
animals; naturally occurring and induced models of human
disease; research applications of animals; and the biology of
laboratory animals.
Phone: 901-754-8620 Fax: 901-753-0046
Internet: http://www.aalas.org/pubs/laonline.htm
Pig International
Pig International is an international journal for swine producers.
It contains information on health topics, nutrition and breeding,
and has many product resources. Pig International is published
monthly.
Watt Publishing, Co.

122 S. Wesley Av., Mt. Morris, Illinois 1054-1497
Phone: 815-734-4171 - Fax: 815-734-4201
internet resources
Many of the associations mentioned previously have links to

other Internet resources relevant for laboratory animal science.
Special types of resources are electronic databases for searching
1999 CRC Press LLC

literature or scientific data. Only a small fraction of what is
available is mentioned below.
Literature resources:
PubMed (MedLine) http://www.ncbi.nlm.nih.gov/pubmed
Grateful Med (MedLine) http://www.nlm.nih.gov/services/igm.html
Scientific resources:
PiGBASE, the genome database of the pig
http://www.projects.roslin.ac.uk/pigmap/ecpigmap.html
US National Coordination Program for Swine Gene Mapping
http://www.genome.iastate.edu/maps/index.html
swine diet and equipment
Resources of swine diet and equipment are so diverse that a

summary is not possible. The majority of swine used in research
originate from agricultural sources, and local directories should
be used. If SPF swine are required, the National SPF Swine
Accrediting Agency can be contacted for local adresses. Minia-
ture swine are generally supplied by specialized laboratory ani-
mal breeding companies. At least two buyer guides specialized
in the laboratory animal field are available:
Lab Animal Buyers' Guide 1999, Lab Animal, 27 (11), 1998.
Published yearly by Lab Animal.
Laboratory Animals Buyers' Guide 1999. Published every
three years by Laboratory Animals, Ltd.
Miniature Swine Resources

Charles River Laboratories (Yucatan, Hanford)
251 Ballardvale Street, Wilmington, MA 01887
Phone: 978-658-6000 - Fax: 800-992-7329
Charles River France (Yucatan)
59 Rue de la Paix, F-76410 Saint Aubin Les Elbeuf, France
Phone: (+33) 2-3296-9110 - Fax: (+33) 2-3577-0999
Harlan Sprague Dawley (Sinclair, Yucatan)
1999 CRC Press LLC

PO Box 29176, Indianapolis, IN 46229-0176
Phone: 317-984-7521 - Fax: 317-894-1840
Ellegaard Gttingen Minipigs (Gttingen)
Soroe Landevej 302, DK-4261 Dalmose, Denmark
Phone: (+45) 58185818 - Fax: (+45) 58185880
Several other breeders in the U.S. produce miniature swine,

among others Panepinto and Associates, S&S Farms, and Lone
Star Laboratory Swine.
Diet Resources
Diet for miniature swine can be obtained from:
Bio-Serv
1 Eighth St., Frenchtown, NJ 08825
Phone: 908-996-2155 - Fax: 908-996-4123
Harlan Telkad
PO Box 44220, Madison, WI 53744-4220
Phone: 608-277-2070 - Fax: 608-277-2066
Purina Mills
PO Box 66812, St. Louis, MO 63166-6812
Phone: 314-768-4592 - Fax: 314-768-4859
Zeigler Bros.
PO Box 95, Gardners, PA 17324
Phone: 717-677-6181 - Fax: 717-677-6826
Special Diet Services
PO Box 705, Witham, Essex CM8 3AB, United Kingdom
Phone: (+44) 1376-511-260 - Fax: (+44) 1376-511-247
Diets can be obtained from several other companies.
1999 CRC Press LLC

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The Laboratory Swine

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Axel Kornerup Hansen, Dr.Vet.Sci., DVM, is professor of

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Helle Juul Rasmussen, DVM, is appointed as a veterinary

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3 MANAGEMENT AND QUALITY ASSURANCE

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Swine are increasingly used as models in biomedical research.

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Order Suborder Family Genus Species

Artiodactyla Suiformes Hippopotamidea Hippopotamus

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Fig. 1.1 Landrace (Photo Leif Schack-Nielsen/Biofoto)

and with English breeds in the late 1800s, established the

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The Yorkshire or Large White

Fig. 1.2 Yorkshire (Photo Leif Schack-Nielsen/Biofoto)

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Fig. 1.6 Yucatan micropig (Photo courtesy of Charles River

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Fig. 1.8 Hanford minipig (Photo courtesy of Charles River Lab-

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The Vietnamese Potbellied Pig

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anatomical and physiological features9, 10, 11, 12

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Parameter Swine Miniature swine

lifespan (yrs) 10-15 10-15 10-15

a) Yucatan micropig, Gttingen and Sinclair minipig

The large intestines are coiled and voluminous. Because of the

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35-55 kga 19 20 70-90 kgb 21

RBC (106/mL) 4.4-8.6 5.30-9.25 5.6-8.8

a) Yucatan micropig, Gttingen and Sinclair minipig

Lymphatic and Endocrine System

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TABLE 1.4: CLINICAL CHEMICAL PARAMETERS (RANGE) OF SWINE, AND

Parameter Swine 22 Miniature swine

Glucose (mg/dL) 48-135 43-133 56-153

a) Yucatan micropig, Gttingen and Sinclair minipig

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Parameter Swine 24 Miniature swine

heart rate 105 10.6 83 15 105 7

a) Yucatan micropig, Gttingen and Sinclair minipig

TABLE 1.6: REPRODUCTION PARAMETERS OF SWINE, AND MINIATURE SWINE

Parameter Swine 7 Miniature swine

sexual maturity 6 4-5 6

a) Yucatan micropig, Gttingen and Sinclair minipig

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An important factor for the successful use of swine in biomedical

At a typical commercial breeding establishment, separate quar-

In the growing quarters, swine are housed in groups of the

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Fig. 2.1 Group pen at a breeding facility with solid concrete

space are not able to maintain a stable dominance order, result-

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Fig. 2.2 Single pen at a research facility with solid concrete

whereas plastic-coated steel and fiberglass preserve heat more