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Information Resources on Swine in Biomedical Research

1990-2000

piglet photo
February 2000
AWIC Resource Series No. 11
Updates
Animal Models in Biomedical Research: Swine, 1994

Editor:
Cynthia P. Smith, M.S.

Featured article by:
M. Michael Swindle, D.V.M. and
Allison C. Smith, D.V.M.

Published by:
United States Department of Agriculture
Agricultural Research Service
National Agricultural Library
Animal Welfare Information Center
10301 Baltimore Avenue
Beltsville, MD 20705-2351
Contact us: http://www.nal.usda.gov/awic/contact.php

Published in cooperation with the Virginia-Maryland Regional College of Veterinary Medicine

Web Policies and Important Links
Photo courtesy of USDA, ARS


Information Resources on Swine in Biomedical Research


Acknowledgements

The staff of AWIC would like to acknowledge the contributions of M. Michael Swindle, D.V.M. Director of the Division of Laboratory Animal Resources and Professor and Chair of the Department of Comparative Medicine, at the Medical University of South Carolina. Dr. Swindle's expertise in swine anesthesia and surgery is world renowned. He is the recipient of the distinguished Smithy Research Award from the American Heart Association and the VonRecum Award from the Academy of Surgical Research. He has published and lectured extensively on swine antomy, anesthesia, analgesia and surgical techniques. His sharing of resources and expert review of this project is greatly appreciated.

We would also like to thank the editors of the Scandinavian Journal of Laboratory Animal Science for permission to load the previously published article Comparative Anatomy and Physiology of the Pig authored by M. M. Swindle, D.V.M. and A. C. Smith, D.V.M., to this online resource.

Special thanks to Barbara Buchanan for editing and loading the final documents.


Introduction

Swine have increasingly become utilized as biomedical research models in the last two decades. This increased use as an animal model is not only a result of regulatory pressure on other large animal species, but also because swine are recognized as a suitable animal model for human disease based upon their comparative anatomy and physiology. Swine are used as general surgical models of most organs and systems, for cardiovascular research including atherosclerosis, for digestive system models, and in recent years in transplantation and xenografic research.

They are being explored as models in many other systems because of the widespread availability of both domestic and miniature breeds. Hand-in-hand with this increase in the number of swine in research, have come technical developments in surgery, anesthesia, husbandry and handling techniques. These technical advancements have made it easier to use this species in research and have also improved the humane care and use of swine by research institutions worldwide.

This resource was developed to provide investigators, laboratory animal veterinarians, technicians, and others, using swine for biomedical purposes with access to baseline literature on common models and procedures. As the resources available on laboratory swine continues to expand, investigators are encouraged to review multiple publications and to find information that supports their particular research needs.


How to Use This Document

This document is divided into three major sections: Comparative Anatomy and Physiology of the Pig; Bibliography; and Web Resources on Swine.

Comparative Anatomy and Physiology of the Pig

This article provides information on the comparative anatomy and physiology of the porcine cardiovascular, digestive, dermal and urinary system. Differences between farm and miniature breeds are discussed. Comparisons and similarities between swine and human anatomy and physiology are also reviewed. The article is followed by a list of reference citations.

Bibliography

The bibliographic section of this document is divided into 29 subsections. Subsections range in topic from anatomy, anesthesia, surgical procedures, body systems, common biomedical models, and husbandry of laboratory swine. Citations in each subsection were compiled from a variety of medical, agricultural, and biological databases and other resources.

Citations were also generously contributed from the personal files of laboratory swine expert, M. Michael Swindle; D.V.M. Citations include NAL call numbers for sources available at the National Agricultural Library (NAL). Information on how to request materials that are included in the collection of the National Agricultural Library (NAL) may be found on the the Request Library Materials page at http://www.nal.usda.gov/services/request.shtml.

Web Resources on Swine

This section contains links to World Wide Web resources organized into eleven different categories: Articles, Pamphlets, and Handbooks; Bibliographies; Books; Courses/Learning Modules/Techniques; General Swine Sites; Genetics and Breeding; Journals; Proceedings; Literature Databases; Model Research; and Organizations. Emphasis was placed on information that would be helpful to researchers, laboratory animal veterinarians, and technicians. Web addresses were current as of August 1, 2000.

To: Top of Document | Acknowledgements | Introduction | How to Use This Document | Comparative Anatomy and Physiology of the Pig
Bibliography | Web Resources on Swine


Comparative Anatomy and Physiology of the Pig

Abstract | Introduction | Cardiovascular and Pulmonary Systems | Digestive System | Urogenital System
Musculoskeletal System | Integumentary and Lymphatic Systems | Central Nervous and Ophthalmic Systems
Discussion | References

Abstract

Swine, Sus scrofa domestics, are widely used in research and testing. Most of the animals are small domestic farm breeds, but miniature swine such as the Yucatan, Hanford and Gottingen are widely used for chronic studies where the significant growth of the domestic breeds would be an issue. They share anatomic and physiologic characteristics with humans that make them a unique and viable model for biomedical research. The cardiovascular anatomy, physiology and response to atherogenic diets have made them a universally standard model for the study of atherosclerosis, myocardial infarction and general cardiovascular studies. Their gastrointestinal anatomy has some significant differences from that of humans, however, the physiology of their digestive processes has made them a valuable model for digestive diseases. The urinary system of swine is similar to humans in many ways, especially in the anatomy and function of the kidneys. Swine are also a standard model for skin and plastic surgical procedures and have been developed as models of transdermal toxicity. The anatomy and physiology of organs such as the liver, pancreas, kidney and heart have also made this species the primary species of interest as organ donors for xenografic procedures. This manuscript reviews the anatomy and physiology of swine as it relates to biomedical research.

Introduction

Swine have been used extensively in biomedical research and the most relevant models have been reviewed in a series of technical proceedings and books in the last two decades (Stanton & Mersmann, 1986; Swindle, 1983; Swindle, 1992; Swindle, 1998; Swindle & Adams, 1988; Tumbleson, 1986; Tumbleson & Schook, 1996).

All swine commonly used in research and testing are Sus scrofa domestics, whether they are farm or miniature breeds. The main difference between breeds is size at sexual maturity. Domestic breeds typically reach 100 kg by 4 months of age and miniature breeds typically range from 25-50 kg at the same age. The predominant breeds of miniature swine used in research are the Yucatan, Hanford, Göttingen and Sinclair Hormel, although dozens of other breeds have been utilized in the scientific literature (Swindle et al, 1994).

The predominant porcine systems studied in biomedical research are cardiovascular, digestive, dermal and urinary. However, a smaller number of models have utilized other systems. This manuscript reviews the relevant anatomy and physiology of the pig as it applies to biomedical research. The discussion is organized by systems with the glandular and endocrine structures discussed with the anatomically associated organs.

Cardiovascular and Pulmonary Systems

The heart of the pig is anatomically similar to humans with a notable exception being the presence of the left azygous (hemiazygous) vein, which drains the intercostal system into the coronary sinus (Swindle et al, 1986). The coronary system is similar to 90% of the human population in anatomy and function. There are no preexisting collateral vessels in the myocardium (Bloor et al, 1992). The heart of a 40-50 kg miniature pig is approximately the same size as an adult human heart. The heart is approximately 0.5% of the body weight at sexual maturity in miniature swine, however, the heart decreases as a percentage of body weight in domestic swine as the animal grows and is approximately 0.3% at the same age as the miniature swine. Differences in heart weight between species of miniature swine have been noted with the Yucatan having a significantly larger heart than the Hanford at the same age (Smith et al, 1990; Swindle et al, 1988). The blood supply to the conduction system is from the posterior septal artery and thus is predominantly right side dominant like the human (Gardner & Johnson, 1988). There are large numbers of adrenergi cholinergic fibers in the AV node and right and left bundle branches. However, nerve cells are sparse in the fibers. The endocardium and epicardium are activated simultaneously because of differences in the distribution of the conduction system. The Purkinje system has large subendocardial fibers. These characteristics give the pig a more neuromyogenic conduction system than the human. However, other species used in cardiac electrophysiology also have anatomic and functional differences in the conduction system from humans as well. Conduction system rates decrease as the animal matures, but in general are more rapid than for humans of equivalent maturity (Gardner & Johnson, 1988); (Stanton & Mersmann, 1986).

The aorta of swine contains a vaso vasorum like humans. It also has a comparable histologic anatomy. However, blood vessels and the atria in swine tend to be more friable than other species, especially in neonates. The blood vessels are also more prone to vasospasm during manipulation. The external jugular vein and sheath are at approximately the same depth as the ventral surface of the cervical vertebrae. The jugular furrow may be visualized running from the ramus of the mandible to the point of the shoulder by pulling the forelimb caudally while the pig is in dorsal recumbency. Many of the peripheral blood vessels are located relatively deep in the tissues compared to other species, however, vascular access may be readily obtained with standard sized needles from the cephalic, external and internal jugular, auricular, anterior abdominal, saphenous and femoral veins with practice. All of these vessels as well as internal abdominal and thoracic vessels may be chronically catheterized surgically (Swindle, 1983; Swindle, 1998; Swindle et al, 1986; Swindle et al, 1988).

Hemodynamically, swine have been demonstrated to be similar in cardiac function to humans. There are variations between breed and age of swine that need to be taken into consideration. For instance, the Yucatan micropig has a significantly higher pulmonary vascular resistance at the same age as the Yucatan and Hanford miniature breeds. The Hanford has a higher systolic blood pressure than either Yucatan under equivalent conditions. When reproducing studies between laboratories, caution should be taken in comparing hemodynamics between different breeds. Animals should be age and weight matched (Smith et al, 1990; Swindle, 1998). The development of atherosclerosis occurs both spontaneously and by experimental induction in swine feed an atherogenetic diet. The metabolism of lipoproteins is similar to humans. Endothelial damage with balloon catheters can be utilized to localize the site of development of the atherosclerotic plaque, however, the distribution of the atherosclerotic plaques will be similar to humans if allowed to develop spontaneously over time. The histology and pathogenesis of the plaques appears to be similar to humans as well (Gal & Isner, 1992; White et al, 1992) .

Swine do have congenital cardiovascular anomalies including ventricular septal defect (VSD), atrial septal defect, patent foramen ovale, patent ductus arteriosus and tricuspid dysplasia. Hypertrophic cardiomyopathy also has a spontaneous occurrence i n some breeds of domestic and miniature swine (Swindle et al, 1992). The model of VSD has been developed as a genetically reproducible model which has been shown to be analogous to human infants with VSD and failure to thrive syndrome. It consistently develops the various morphologies of high membranous defects and may be useful for the study of interventional closure of the defects. Congenital shunts may also be created by use of angioplasty balloon techniques. If shunts are reopened in neonates with balloon catheters they will remain open and develop volume overload hypertrophy. They also develop pressure overload hypertrophy following banding of the great vessels of the heart like other species (Swindle, 1998).

Most of the cardiovascular models in swine (Stanton & Mersmann, 1986; Swindle, 1998) are related to testing of interventional catheter devices (Gal & Isner, 1992; Swindle, 1998), atherosclerosis White et al, 1992), myocardial infarction (Bloor et al, 1992; (Gardner & Johnson, 1988), coronary blood flow (Bloor et al, 1992; (Gardner & Johnson, 1988), intracardiac electrophysiology (Brownlee et al; (Smith et al, 1997) and cardiovascular surgery (Swindle, 1998; Swindle et al, 1986), predominantly with the implantation of biomechanical devices (Gal & Isner, 1992; Mehran et al, 1991).

The characteristics that have led to the use of swine over other species for these models are related to the anatomic and physiologic characteristics described above. The porcine model develops an infarction pattern like the human and develops arrhythmogenic activity with reperfusion. The canine model of infarction already has an existing collateral blood supply, but may represent the portion of the human population which has slowly developed collateral circulation due to gradual occlusion of a coronary artery. Gradual occlusion may be created in swine by causing endothelial damage with an angioplasty balloon and feeding an atherogenic diet of 2% cholesterol. The pattern of infarction and healing of the myocardium is almost identical to humans (Bloor et al, 1992; (Gal & Isner, 1992; (Gardner & Johnson, 1988); (Stanton & Mersmann, 1986; Swindle, 1998; White et al, 1992).

Likewise, the wound healing characteristics in the cardiovascular system mimic these in man following implantation of some devices, such as intracoronary stents. Unlike other models they develop coronary restenosis syndrome (Swindle, 1998; White et al, 1992). For intravascular healing, investigators may be required to use multiple models since no single species is exactly analogous to humans. The pig has the advantages of predictable size and platelet function, unlike the dog. Even the primate models are not exactly analogous. Wound healing in the myocardium has typically used swine, dogs and sheep. The myocardial wound healing characteristics of swine are more analogous to humans than sheep models since ruminants healing is characterized by the formation of collagenous scars (Mehran et al, 1991); National Institutes of Health, 1985; Von Recum, 1986).

The lungs are composed of apical, middle and diaphragmatic lobes with an additional accessory lobe for the right lung. The interlobular fissures are incomplete. The larynx is prominent with a large vestibule and lateral and middle ventricles that create a caudal narrowing of the structure. The trachea courses from approximately C3-4 into the thorax. The apical lobe of the right lung has a bronchus that stems from the trachea cranial to the tracheal bifurcation which supplies the other lobes of the lung. The bronchial tree divisions are typical of other species (Swindle, 1998). Functional studies of the airway, including neurochemical anatomy and smooth muscle function, make them useful in models of acute respiratory distress syndrome and asthma. The neonatal development of the lungs and airways is useful for extrapolation to humans (Brown & Terris, 1996). The thyroid gland is located on the ventral surface of the trachea at the thoracic inlet rather than near the larynx. The thymus gl and is located in the cranial thorax and neck coursing along the trachea. The paired parathyroid glands are located near the cranial thymus rather than the thyroid (Swindle, 1983; Swindle, 1998).

Digestive System

The digestive system of swine has anatomic differences from humans fig. 2, fig. 3, fig. 4, however, the physiology of digestion remains similar to humans. Swine are true omnivores.

The dental formula for swine is 2(I 3/3, C 1/1, P 4/4)=32 for deciduous teeth. For permanent teeth it is 2(I 3/3, C 1/1, P 4/4, M 3/3)=44. A full set of permanent teeth is usually present by 18 months of age (Swindle, 1998).

The salivary glands of the pig are large and consist of paired parotid, mandibular and sublingual glands. The parotid duct enters the oral cavity opposite the juncture of the premolars and molars. The mandibular and sublingual glandular ducts enter t he floor of the mouth near the frenulum. Buccal glands are located opposite the cheek teeth. The parotid gland is serous, the sublingual glands are mucous and the rest are mixed for glandular secretions. The tonsils are embedded in the oropharynx (Schantz et al, 1996).

There is a pharyngeal diverticulum dorsal to the larynx in the caudal portion of the nasopharynx. The muscular layers of the esophagus are mainly composed of smooth muscle until its termination cranial to the esophageal sphincter when it becomes partially striated muscle. The stomach is typical of monogastric animals with the exception of the torus pyloricus, which is a muscular outpouching near the pyloric sphincter. The small intestine is long and located mainly in the right side of the abdomen. The mesenteric vessels form a vascular arcade in the subserosa rather than in the mesentery as in other species. Mesenteric lymph nodes are prominent. The majority of the large intestine is located in the spiral colon in the left upper quadrant of the abdomen. it consists of the cecum, ascending, transverse and a portion of the descending colon coiled tightly into a series of centripetal and centrifugal coils. The outer coil contains two tenia. The descending colon passes caudally along the left abdominal wall to the rectum and anal sphincter. Neither a true sigmoid flexure nor an appendix are present. The pigs intestinal length is approximately 30 times its body length (Schantz et al, 1996).

The liver contains six lobes and a gall bladder. The lobules of the liver are separated by fibrous septae. The common bile duct enters the duodenum separately from the pancreatic duct caudal to the pylorus. The pancreas is extensive and the tail follows the lesser curvature of the stomach from the spleen to the proximal duodenum. The body encircles the superior mesenteric vein and extends dorsally to the left kidney. The pancreatic ducts in the tail and body join at the juncture of the two lobes to enter the duodenum distal from the bile duct. The islet cells are relatively indistinct histologically. Functionally, both the liver and pancreas are similar to humans (Mullen et al, 1992; Pennington & Sarr, 1988; (Schantz et al, 1996).

In spite of the anatomic differences, the pig has been used extensively as a gastrointestinal model. Most of the classical models involving the digestive system have been related to nutritional studies to study digestion of the pig and for studying human digestive phenomena. They will readily ingest such test substances as alcohol in its various forms. The metabolic functions, intestinal transport times, and characteristics of absorbtion of nutrients have made them useful in basic nutritional research. Other specific functional characteristics of swine that relate directly to humans include ion transport and motility, neonatal development of the gastrointestinal tract and splancnic blood flow characteristics. Development of host defenses and endotoxi c shock studies have made them useful as biomedical models in these areas. Like the human, these physiologic characteristics of the gastrointestinal tract are probably due to the omnivorous diet that they consume, unlike that of carnivores, ruminants, rabbits and rodents (Brown & Terris, 1996; Reeds & Odle, 1996; Tumbleson, 1986; Tumbleson & Schook, 1996).

More recently endoscopic and laparoscopic surgical models have been developed and used extensively in the pig. The size and function of structures such as the biliary system and pancreatic duct make them amenable for studying human sized equipment an d biomaterial implants. Surgical modifications have made the intestinal tract amenable to the study of surgical and chronic fistulation procedures ( Swindle, 1998; Swindle & Adams, 1988).

Swine have a similar cytochrome P450 system to humans except for the absence of CYP2C19 and CYP2D6 (Skaanild & Friis, 1997). However, metabolically the liver functions similar to humans and has been used for xenoperfusion protocols for humans in hepatic comas (Collins et al, 1994; Swindle, 1998).

Urogenital System

The female reproductive system has a bicornuate uterus with torturous fallopian tubes. The fallopian tubes of an adult female are the same diameter as those of humans, however they are much longer. The sow has an estrous cycle of 2021 days rather tha n a menstrual cycle. Domestic farm breeds have larger litters, usually of 8-12 pigs, than miniature pigs which typically have litters of 4-6. The numbers are variable depending upon the breed and the parity of the sow. The gestation period of 112-114 days allows sows to have up to three litters per year. Uterine placentation is diffuse epitheliochorial. There are typically 12-14 paired mammary glands on the ventral abdomen (Swindle, 1998; Tumbleson, 1986; Tumbleson & Schook, 1996).

The sow has been used in studies of fetal surgery to create models that mimic the human situation. Even though the placentation is unlike humans, the physiologic characteristics of transplacental transfer of antiarrhythmics has been shown to be more similar to the human situation than the traditional ewe model. This transplacental transfer of therapeutic agents may make the sow a predictable model of teratogenicity and efficacy of pharmaceutic agents (Wiest et al, 1996).

The male reproductive system has the same structures as humans, however, the accessory sex glands which predominate are different. The scrotum and testicles are located in the perineal region. The penis is fibromuscular with a sigmoid flexure on the ventral abdomen. The penis has a corkscrew shaped tip. The prepuce is located caudal to the umbilicus and has a preputial diverticulum which contains foul smelling urine and secretory material. The accessory sex glands are: vesicular glands, prostate gland, and bulbo urethral glands. The, vesicular glands are prominent and located at the neck of the bladder. The prostate and bulbourethral glands are relatively small. The shape of the penis and the preputial diverticulum make it impossible to catheterize a male pig through the penile opening. Catheterization has to be performed in the perineal urethra percutaneously (Swindle, 1983); Swindle, 1998).

The kidneys of the pig are more like humans in anatomy and function than most other species of animals. The left kidney is cranial to the right and both are located ventrally to the transverse processes of LI-4. The adrenal glands are located near the cranial poles of both kidneys and the right gland is intimately associated with the wall of the postcava. The kidneys are multirenculate and multipapillate like humans. The blood supply to the kidney divides transversely between the cranial and caudal poles rather than longitudinally like most species (Brown & Terris, 1996), Pennington, 1992; Sachs, 1992; Terris, 1986).

The bladder is thin walled, but functionally is similar to other species. The innervation is derived from S2-4. The pelvic urethra courses along the ventral floor of the pelvis. The female urethra opens on the ventral floor of the vagina about 1/3 of the distance to the cervix. The male urethra courses through the penis as described above (Swindle, 1983; Swindle, 1998; Swindle & Adams, 1988).

Swine have been used in studies of developmental and pediatric urology because of the unique anatomy of the kidneys which allows them to develop vesicoureteral and intrarenal reflux (Swindle, 1998; Swindle & Adams, 1988; Terris, 1986). The kidney has also been used extensively in transplantation biology, including xenografic studies (Institute of Medicine, 1996; Pennington, 1992; Sachs, 1992; Swindle, 1998).

The anatomic and physiologic characteristics of the porcine kidney may make it useful for the study of pharmacologic agents since the anatomy of the kidney is more similar to humans than even primates. Swine can be utilized in studies of renal hypertension and can be developed as a model of intact renal DOCA salt induced hypertension or as surgical ablation models of renin induced hypertension (Swindle, 1998; Swindle & Adams, 1988; Terris, 1986).

Musculoskeletal System

The skeletal system of the pig is massive with relatively thick cortical bone. This is consistent with the support of a rapidly growing animal with a relatively small stature. The Vertebral formula for swine is C7, T14-15, L6-7, S4, Cy2O-23. There ar e 7 sternal and 7 asternal ribs. If a 15th rib is present, it is floating. The principle digits of the pig are III and IV. Digits 11 and V are vestigial and form the dewclaws. Swine are considered to be ungulent or hooved animals. The long bone epiphyses close by 3-4 years in domestic farm breeds and generally 1-2 years earlier in the miniature breeds (Adams, 1988; Donovan et al, 1993; Swindle, 1998).

The muscles of the pig tend to be massive which is consistent with its primary use as a food source. The muscles have a predominance of Type IIB fibers with lesser numbers of Types IIA and IIC. The quadriped locomotion of swine is different from humans and the muscles reflect this characteristic in their morphology like other quadrupeds (Adams, 1988).

Because of the massive nature of the musculoskeletal system and the quadriped locomotion characteristics, swine have rarely been used in studies of these systems. Recently, there has been increased interest in the model for temporomandibular joint studies as well as bone healing and grafting techniques (Adams, 1988; Bermejo et al, 1993; Donovan et al, 1993; Swindle, 1998).

Integumentary and Lymphatic Systems

Swine are relatively hairless animals with a fixed skin tightly attached to the subcutaneous tissues like humans. Overall, the skin is thicker and less vascular than humans, however, the cutaneous blood supply characteristics are similar. Apocrine sweat glands are absent. Fat cells may be located in the dermis. As the animal grows a substantial amount of subcutaneous fat is deposited. The skin tends to be thicker on the neck and dorsum of the animal (Bolton et al, 1988; Chvapil & Chvapil, 1992; Kerrigan et al, 1986; Montiero-Riviere & Riviere, 1996).

The lymph nodes of the pig have a unique histologic structure. The typical cortex and medulla are reversed with the germinal centers being located in the interior of the gland (Swindle, 1983; Swindle, 1998).

The anatomy and physiology of the cutaneous blood supply and the wound healing characteristics have made the pig a standard model for plastic surgical and wound healing studies (Kerrigan et al, 1986; Mertz et al, 1986). Recently interest has developed in the pig as a model of dermal and transdermal toxicology Montiero-Riviere, 1986); Montiero-Riviere & Riviere, 1996; Riviere et al, 1986). Besides the anatomic similarities swine are equivalent to primates for percutaneous absorbtion studies and have similar lipid biophysical properties, epidermal turnover kinetics and carbohydrate metabolism in the skin Montiero-Riviere & Riviere, 1996).

Central Nervous and Ophthalmic Systems

The brain is encased in a cranial vault formed by the massive cranial bones. The brain is relatively large with structures typical of those of other species. The spinal cord terminates at S2-3 with the origin of the cauda equina. The anatomy of the blood supply to the brain and spinal cord is similar to humans. A stereotactic atlas of the pig brain has been published (Stodkilde-Jorgensen, 1986; Swindle, 1998).

The eye contains a nictitating membrane, Bowman's membrane and Descemet's membrane. Draining for the lacrimal glands is by either one or two puncta in the conjunctiva. The nictitating membrane contains a Harder's gland. The globe is relatively deep i n the orbit with seven extraocular muscles. The eye has an open field of vision with a pupil and retina that resembles humans. The tapetum is absent (Adams, 1988).

Relatively little work has been performed to study the function of the central nervous system in this species. Because of the massive bone structure, surgical access to the brain and spinal cord is difficult. However, the brain development of swine a nd the similar topical, histologic and vascular anatomy make them useful as general mammalian models. Hypophysectomy and cannulation techniques have been described (Swindle, 1998).

Discussion

This review of the anatomy of the pig details the unique characteristics that differentiate it from other species. It also describes characteristics that are significant when using the animal as a biomedical model for humans. More detailed descriptio ns of the anatomy are available (Getty, 1975; Gilbert, 1966; Leman et al, 1992; Poppesko, 1977; Sack, 1982).

The anatomic and physiologic characteristics of swine have made them a valuable animal model of human diseases as well as a model for general mammalian physiology. The systems that are most often studied experimentally are the cardiovascular, digestive, integumentary and urinary ((Stanton & Mersmann, 1986; Swindle, 1983; Swindle, 1992; Swindle, 1998; Swindle & Adams, 1988; Tumbleson, 1986; Tumbleson & Schook, 1996). Interest in the development of models using other systems is rapidly increasing because of the decreased availability and rising costs of other species such as nonhuman primates and dogs. It is likely that comparative descriptions of other systems will appear increasingly in the literature. The interest in swine as xenografic transplant donors is also likely to increase their characterization physiologically and at the molecular level (Institute of Medicine, 1996; Swindle, 1998).

Swine can not replace all other large animal models in biomedical research, however, they are at least as similar to humans for many types of studies which use species such as ruminants and dogs. Consequently, they can be selected as a general mammalian model unless other models have been shown to develop unique physiologic responses to experimental manipulations.

References

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Mullen, Y, Y Taura, M Nagata, K Miyazawa & E Stein: Swine as a model for pancreatic betacell transplantation. In: Swindle, MM (ed.), Swine as Models in Biomedical Research, Ames, IA: Iowa State University Press, pp. 1634, 1992.

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Pennington, LR: Renal transplantation in swine. In: Swindle, MM (ed.), Swine as Models in Biomedical Research, Ames, IA: Iowa State University Press, pp. 35-43, 1992.

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Reeds, P & J Odle: Pigs as models for nutrient functional interaction. In: Tumbleson, ME and Schook LB (eds.), Advances in Swine in Biomedical Research, Vol. 2, NY: Plenum Publishers, pp. 709-711, 1996.

Riviere, JE, KF Bowman & NA Monteiro-Riviere: The isolated perfused porcine skin flap: A novel animal model for cutaneous toxicologic research. In: Swine in Biomedical Research, Vol. 1, Tumbleson, ME (ed.). NY: Plenum Press, pp. 657-666, 1986.

Sachs, DH: MHC-homozygous miniature swine. In: Swindle, MM (ed.), Swine as Models in Biomedical Research, Ames, IA: Iowa State University Press, pp. 3-15, 1992.

Sack, WO: Essentials of Pig Anatomy. In: Harowitz/ Kramer Atlas of Musculoskeletal Anatomy of the Pig, Veterinary Textbooks, Ithaca, NY, 1982.

Schantz, LD, K Laber-Laird, S Bingel & M Swindle: Pigs: Applied anatomy of the gastrointestinal tract, In: Jensen, SL, Gregersen, H, Moody, F and Shokouh-Amiri, MH (eds.), Essentials of Experimental Surgery: Gastroenterology, NY. Harwood Academic Publishers, pp. 2611-2619, 1996.

Skaanild, MT & C Friis: Characterization of the P450 system in Göttingen minipigs, Pharm Toxicol 80(Suppl 11): 28-33, 1997.

Smith, AC, B Knick, M Swindle & PC Gillette: A technique for conducting non-invasive cardiac electrophysiology studies in swine. J Invest Surg, 10(1-2): 25-30, 1997.

Smith, AC, FG Spinale & MM Swindle: Cardiac function and morphology of Hanford miniature swine and Yucatan miniature and micro swine. Lab Anim Sci. 40(l): 47-50, 1990.

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Swindle, MM, AC Smith & BJS Hepburn: Swine as models in experimental surgery. J Invest Surg. l(l): 65-79, 1988.

Swindle, MM: Swine as Models in Biomedical Research, Ames IA: Iowa State University Press, 1992.

Swindle, MM, RP Thompson, BA Carabello, AC Smith, C Green & PC Gillette: Congenital cardiovascular disease. In: Swindle, MM (ed.), Swine as Models in Biomedical Research, Ames, IA: Iowa State University Press, pp. 176-184, 1992.

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White, CJ, SR Ramee, AK Banks, D Wiktor & HL Price: The Yucatan miniature swine: An atherogenic model to assess the early potency rates of an endovascular stent. In: Swindle, MM (ed.), Swine as Models in Biomedical Research, Ames, IA: Iowa State University Press, pp. 156-162, 1992.

Wiest, DB, MM Swindle, SS Garner, AC Smith & PC Gillette: Pregnant Yucatan miniature swine as a model for investigating fetal drug therapy. In: Tumbleson, M and Schook, L (eds.), Advances in Swine in Biomedical Research, Vo l. 2, p. 629-635, 1996.

To: Top of Document | Acknowledgements | Introduction | How to Use This Document | Comparative Anatomy and Physiology of the Pig
Bibliography | Web Resources on Swine


Bibliography


 Anatomy  |   Anesthesia  |  Atherosclerosis  |  Cardiopulmonary Bypass  |  Cardiovascular 
 Central Nervous System  |  Endoscopic and Laparoscopic Surgery  |  Fetal  |  Gastrointestinal 
 General  |  Head and Neck  |  Hemodynamics, Cardiovascular Catheterization and Electrophysiology 
 Husbandry  |  Immunology  |  Kidney and Urology  |  Liver  |  Malignant Hyperthermia  |  Musculoskeletal 
 Obstetrics and Gynecology  |  Ophthalmology  |  Pancreas  |  Pediatrics and Neonatal  |  Physiology  |  Pulmonary 
 Reproductive  |  Skin and Wound Healing  |  Surgery  |  Transplantation  |  Xenografic Transplant





ANATOMY

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Frandson, R.D. (1981). Anatomy and Physiology of Farm Animals, 3rd ed., Philadelphia: Lea and Febiger, Philadelphia.
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Frandson, R.D. and T.L. Spurgeon (1992). Anatomy and Physiology of Farm Animals, 5th ed., Philadelphia: Lea and Febiger, Philadelphia.
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Gade, J., Norgaard, M.A., Andersen, C.B., et al. (Feb. 1999). The porcine bronchial artery: surgical and angiographic anatomy. Journal of Anatomy 194(Part 2): 241-247.

Getty, R. (1975). Porcine. In: Sisson and Grossman's The Anatomy of Domestic Animals, S. Sisson, J.D. Grossman, and R. Getty (eds.), Vol. 2, Philadelphia: W.B. Saunders, pp. 1215-1422.
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Gilbert, S.G. (1966). Pictoral Anatomy of the Fetal Pig, 2nd ed. Seattle: University of Washington Press.

Popesko, P. (1977). Atlas of Topographical Anatomy of the Domestic Animals, Vol. 1, 2nd ed., Philadelphia: W.B. Saunders Company.
NAL call number: SF761.P63 1977

Sack, W.O. (1982). Essentials of pig anatomy. In: Harowitz/Kramer Atlas of Musculoskeletal Anatomy of the Pig, Veterinary Textbooks, Ithaca, NY.

Salinas-Zeballos, M.E., G.A. Zeballos, and P.M. Gootman (1986). A stereotaxic atlas of the developing swine (Sus scrofa) forebrain. In: Swine in Biomedical Research, M.E. Tumbleson (ed.), Vol. 2, NY: Plenum Publishers, pp. 887-906.
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Schantz, L.D., K. Laber-Laird, S. Bingel, and M. Swindle (1996). Pigs: Applied anatomy of the gastrointestinal tract. In: Essentials of Experimental Surgery: Gastroenterology, S.L. Jensen and H. Gregersen (eds.), NY: Harwood Academic Publishers, pp. 2611-2619, ISBN:3-7186-5496-2.

Sisson, S. (1975). Appendages. In: Sisson and Grossman's The Anatomy of Domestic Animals, S. Sisson, J.D. Grossman, and R. Getty (eds.), 5th ed., Vol. 2, Philadelphia: W.B. Saunders, pp. 1222-1230.
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Sisson, S. and S.E. St. Clair (1975). Porcine digestive system. In: Sisson and Grossman's The Anatomy of Domestic Animals, S. Sisson, J.D. Grossman, and R. Getty (eds.), 5th ed., Vol. 2, Philadelphia: W.B. Saunders, pp. 1268-1282.
NAL call number: SF761.S65 1975

Swindle, M.M. (1998). Biology, husbandry, handling, and anatomy. In: Surgery, Anesthesia and Experimental Techniques in Swine, Ames, IA: Iowa State University Press, pp. 3-32.
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Swindle, M.M. and D.L. Bobbie (1987). Comparative anatomy of the pig. Charles River Technical Bulletin 4(1): 1-4.

Swindle, M.M. and A.C. Smith (1998). Comparative anatomy and physiology of the pig. Scandinavian Journal of Laboratory Animal Science 25, 1-10.
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Truex, R.C. and M.Q. Smythe (1965). Comparative morphology of the cardiac conduction tissue in animals. Annals of the New York Academy of Sciences 127: 19-23.
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ANESTHESIA

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Adam, H.K., J.B. Glen, and P.A. Hoyle (1980). Pharmacokinetics in laboratory animals of ICI 35 868: A new i.v. anaesthetic agent. British Journal of Anaesthesia 52(8): 743-746.

Akeson, J., S. Bjorkman, K. Messeter, and I. Rosen (1993). Low-dose midazolam antagonizes cerebral metabolic stimulation by ketamine in the pig. Acta Anaesthesiologica Scandinavica 37: 525-531.

Akeson, J., S. Bjorkman, K. Messeter, I. Rosen, and M. Helfer (1993). Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig. Acta Anaesthesiologica Scandinavica 37: 211-218.

Andersen, H., R. Fosse, K. Kuiper, and J. Nordrehaug (1998). Ketorolac (Toradol(R)) as an analgesic in swine following transluminal coronary angioplasty. Laboratory Animals 32: 307-315.
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Becker, M. (1986). Anesthesia in Gottingen miniature swine used for experimental surgery. Laboratory Animal Science 36(4): 417-419.
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Benson, G.J. and J.C. Thurmon (1979). Anesthesia of swine under field conditions. Journal of the American Veterinary Medical Association 174(6): 594-596.
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Blobner M., R. Bogdanski, S. Jelen-Esselborn, J. Henke, W. Erhard, and E. Kochs (Feb. 1999). Visceral resorption of intra-abdominal insufflated carbon dioxide in swine. [Viszerale Resorption von intraabdominell insuffliertem Kohlendioxid beim Schwein.] Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie 34(2): 94-99.

Blum, J.R. (1988). Laboratory animal anesthesia. In: Experimental Surgery and Physiology: Induced Animal Models of Human Disease, M.M. Swindle and R.J. Adams (eds.), Baltimore, MD: Williams and Wilkins, pp. 329-345.
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Bollen, P.J., A.K. Hansen, and H.J. Rasmussen (2000). Veterinary care: anesthesia and analgesia. In: The Laboratory Swine, Boca Raton, FL: CRC Press LLC, pp. 61-82, ISBN: 0849310350.

Bolin, S.R., L.J. Runnels, and D.P. Bane (1992). Chemical restraint and anesthesia. In: Diseases of Swine, A.D. Leman, B. Straw, R.D. Glock, W.L. Mengeling, R.H.C. Penny, and E. Scholl (eds.), 7th ed., Iowa State University Press, Ames, IA, pp. 933-942.
NAL call number: SF971 D57 1992

Braun, W. (1993). Anesthetics and surgical techniques useful in the potbellied pig. Veterinary Medicine 88: 441-447.
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Breese, C.E. and N.H. Dodman (1984). Xylazine-ketamine-oxymorphone: An injectable anesthetic combination in swine. Journal of the American Veterinary Medical Association 184(2): 182-183.
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Brower, R.W. and R.G. Merin (1979). Left ventricular function and compliance in swine during halothane anesthesia. Anesthesiology 50(5): 409-415.

Burrows, F.A., J.B. Norton, R.E. Creighton, and J. Fewel (1988). Hemodynamic effect of ketamine in swine with mature autonomic nervous system. Anaesthesiologie und Reanimation 13: 169-75.

Busund, R., L. Balteskard, G. Ronning, K. Hogasen, and A. Revhaug (1995). Fatal myocardial depression and circulatory collapse associated with complement activation induced by plasma infusion in severe porcine sepsis. Acta Anaesthesiolgica Scandinavica 39: 100-108.

Calzia, E., W. Stahl, T. Handschuh, T. Marx, G. Froba, M. Georgieff, and P. Rademacher (March 1999). Continuous arterial P(O2) and P(CO2) measurements in swine during nitrous oxide and xenon elimination: prevention of diffusion hypoxia. Anesthesiology 90(3): 829-834.

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Cheng, D., J. Moyers, R. Knutson, M. Gomez, and J. Tinker (1992). Dose-response relationship of isoflurane and halothane versus coronary perfusion pressures. Anesthesiology 76(1): 113-122.

Christiansen, I. J. (1976). Caesarean section in sows anesthetized with Azaperone and Metomidate [Sedaperone og Hypnodil til anaestesi ved kejsersnit pa sooer]. Nordisk Veterinaemedicin 28: 88-99.
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Conradie S., A. Coetzee, and J. Coetzee (Jan. 1999). Anesthetic modulation of myocardial ischemia and reperfusion injury in pigs: comparison between halothane and sevoflurane. Canadian Journal of Anaesthesia 46(1): 71-81.

Coppock, R.W., S.P. Swanson, H.B. Gelberg, and G.D. Koritz (1987). Pharmacokinetics of diacetoxyscirpenol in cattle and swine: Effects of halothane. American Journal of Veterinary Research 48(4): 691-695.
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Crane, L., N. Gootman, and P.M. Gootman (1975). Age-dependent cardiovascular effects of halothane anesthesia in neonatal pigs. Archive Internationales de Pharmacodynamie et de Therapie 214(2): 180-187.

Danneberg, P., R. Bauer, K. Boke-Kuhn, W. Hoefke, F.J. Kuhn, E. Lehr, and A. Walland (1986). General pharmacology of brotizolam in animals. Arzneimittel-Forschung 36(3A): 540-51.

Dantzer, R., R.M. Bluthe and A. Tazi (1986). Stress-induced analgesia in pigs. Annales de Recherches Veterinaires 17: 147-151.
NAL call number: SF602 A5

Diederen, W. and R. Kadatz (1981). Effects of AR-L 115BS, a new cardiotonic compound on cardiac contractility, heart rate and blood pressure in anaesthetized and conscious animals. Arzneimittel-Forschung. Drug Research 31(1a): 146-150.
NAL call number: RS1 A7

Dimigen, J. and I. Reetz (1970). Clinical trials with analgesia in the swine using the neuroleptic Azaperone and the hypnotic Metomidate. 1 [Versuche zur Schmerzausschaltung beim Schwein mit dem Neuroleptikum Azaperon und dem Hypnotikum Metomidat. 1.] Deutsch Tierarzliche Wochenschrift 77: 470-473.
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Dyess, D.L., E. Tacchi, R.Q. Powell, J.L Ardell, W.S. Roberts, and J.J. Ferrara (1994). Development of a protocol to provide prolonged general anesthesia to pregnant sows. Journal of Investigative Surgery 7: 235-242.

Eger, E., B. Johnson, R. Weiskopf, M. Holmes, N. Yasuda, A. Targ, and I. Rampil (1988). Minimum alveolar concentration of I-653 and isoflurane in pigs: Definition of a supramaximal stimulus. Anesthesia and Analgesia 67(12): 1174-1176.

Eger, E. II (1984). Respiratory effects of nitrous oxide. In: Nitrous Oxide, New York, NY, Elseiver, pp. 109-123, ISBN: 0-444-00860-8.

Ehler, W.J., J.W. Mack, D.L. Brown, and R.F. David (1985). Avoidance of malignant hyperthermia in a porcine model for experimental open heart surgery. Laboratory Animal Science 35(2):172-175.
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Eisele, P.H., L. Talken, and J.H. Eisele (1985). Potency of isoflurane and nitrous oxide in conventional swine. Laboratory Animal Science 35(1): 76-78.
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Ennis, M., C. Schneider, E. Nehring, and W. Lorenz (1991). Histamine release induced by opioid analgesics: a comparative study using porcine mast cells. Agents Actions 33: 20-22.

Erhardt, W., C. Ring, H. Kraft, A. Schmid, H.M. Weinmann, R. Ebert, B. Schlager, M. Schindele, R. Heinze, N. Lomholt, et al. (1989). CO2-stunning of swine for slaughter from the anesthesiological viewpoint. [Die CO2-Betaubung von Schlachtschweinen aus anasthesiologischer Sicht]. DTW Deutsche Tierarztliche Wochenschrift 96: 92-99.
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Errando, C.L., C. Sifre, S. Moliner, J.C. Valia, et al. (March-April 1999). Subarachnoid ketamine in swine--pathological findings after repeated doses: acute toxicity study. Regional Anesthesia and Pain Medicine 24(2): 146-52.

Fay, R. and E. Gallant (1990). Halothane sensitivity of young pigs in vivo and in vitro. American Physiological Society 259(1, Part2):R133-R138.

Flecknell, P.A. (1984). The relief of pain in laboratory animals. Laboratory Animals 18(2): 147-160.
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Flecknell, P.J. (1997). Medetomidine and antipamezole: Potential uses in laboratory animals. Laboratory Animals 26(2): 21-25.
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Flecknell, P.A. (1996). Laboratory Animal Anaesthesia: A Practical Introduction for Research Workers and Technicians, 2nd ed., London; San Diego: Academic Press, 274p.
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Foster, P.S., K.C. Hopkinson, and M.A. Denborough (1992). Propofol anaesthesia in malignant hyperpyrexia susceptible swine. Clinical and Experimental Pharmacology and Physiology 19(3): 183-186.

Ganter, M. and M. Kanngiesser (1991). Effect of ketamine and its combinations with xylazine and climazolam on the circulation and respiration in swine. [Auswirkung von Ketamine und dessen Kombinationen mit Xylazin und Climazolam auf Kreislauf und Atmung beim Schwein.] Zentralblatt fur Veterinarmedizin A 38: 501-509.
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Ganter, M. and K. Ruppert (1990). The effect of the anesthetic Tilest in swine. [Uber die Wirkung des Anasthetikums Tilest beim Schwein.] DTW Deutsche Tierarztliche Wochenschrift 97: 360-364.
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Ganter, M., K. Ruppert, and M. Kanngiesser (1990). The development of a residue-poor anesthesia in swine. [Untersuchungen zur Entwicklung einer belastungsarmen Anästhesia beim Schwein.] Berliner Muenchener Tierarztliche Wochenschrift 103: 341-348.

Garrido S., M. Fraga , M.J. Martin, and J. Belda (1999). Malignant hyperthermia during desflurane-succinylcholine anesthesia for orthopedic surgery. Anesthesiology 90(4): 1208-1209.

Geers, R., C. Decanniere, H.Ville, P.V. Hecke, V. Goedseels, L. Bosschaerts, J. Deley, S. Janssens, and W. Nierynck (1992). Identification of halothane gene carriers by use of in vivo 31P nuclear magnetic resonance spectroscopy in pigs. American Journal of Veterinary Research 53: 1711-1714.
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Gelman, S., E. Dillard, and E.L. Bradley (1987). Hepatic circulation during surgical stress and anesthesia with halothane, isoflurane, or fentanyl. Anesthesia and Analgesia 66(10): 936-943.

Gilbert, M., M. Mori and E. Myhre (1989). Hemodynamic dose-responses to halothane and isoflurane are different in swine with and without critical coronary artery stenosis. Anesthesia and Analgesia 68(6): 752-758.

Gilbert, M., S. Roberts, M. Mori, R. Blomberg, and J.H. Tinker (1988). Comparative coronary vascular reactivity and hemodynamics during halothane and isoflurane anesthesia in swine. Anesthesiology 68(2): 243-253.

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Glen, J.B., G.E. Davies, D.S. Thomson, S.C. Scarth, and A.V. Thompson (1979). An animal model for the investigation of adverse responses to IV anaesthetic agents and their solvents. British Journal of Anaesthesia 51(9): 819-827.

Gootman, P.M., H.L. Cohen, A.M. Steele, A.L. Sica, G. Condemi, M.R. Gandhi, and L.P. Eberle (1990). Effects of anesthesia on efferent phrenic activity in neonatal swine. Brain Research 522: 131-134.

Gordh, T. Jr., U. Feuk, and K. Norlen (1986). Effect of epidural clonidine on spinal cord blood flow and regional and central hemodynamics in pigs. Anesthesia and Analgesia 65: 1312-1318.

Haasio, J., M.T. Pitkanen, J. Kytta, and P.H. Rosenberg, (1990). Treatment of bupivacaine-induced cardiac arrhythmias in hypoxic and hypercarbic pigs with amiodarone or bretylium. Regional Anesthesia 15: 174-179.

Hall, G.M., C. Young, A. Holdcroft, and J. Alaghband-Zadeh (1978). Substrate mobilization during surgery. A comparison between halothane and fentanyl anesthesia. Anesthesiology 33(10): 924-930.

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Harrison, G.G. and D.F. Morrell (1980). Response of MHS swine to i.v. infusion of lignocaine and bupivacaine. British Journal of Anaesthesia 52: 385-387.

Harrison, G.G., D.F. Morrell, V. Brain, and G.G. Jaros (1987). Acute calcium homeostasis in MHS swine. Canadian Journal of Anaesthesia 34: 377-9.

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Henrikson, H., M. Jensen Waern, and G. Nyman (1995). Anaesthetics for general anaesthesia in growing pigs. Acta Veterinaria Scandinavica 36: 401-411.
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Hermansen, K., L.E. Pedersen, and H.O. Olesen (1986). The analgesic effect of buprenorphine, etorphine and pethidine in the pig: a reandomized double blind cross-over study. Acta Pharmacologica et Toxicologica 59(1): 27-35.

Hickey, R.F. (1994). Regional vasodilating properties of isoflurane in normal swine myocardium. Anesthesiology 80: 574-581.

Holmes, M., R. Weiskopf, E. Eger, B.H. Johnson, and I.J. Rampil (1990). Hepatocellular integrity in swine after prolonged desflurane (I-653) and isoflurane anesthesia: evaluation of plasma alanine aminotransferase activity. Anesthesia and Analgesia 71(3): 249-253.

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Ko, J.C., B.L. Williams, E.R. Rogers, L.S. Pablo, W.C. McCaine, and C.J. McGrath, (1995). Increasing xylazine dose-enhanced anesthetic properties of telazol-xylazine combination in swine. Laboratory Animal Science 45: 290-294.
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Ko, J.C.H., B.L. Williams, V.L. Smith, C.J. McGrath, and J.D. Jacobson (1993). Comparison of Telazol, Telazol-Ketamine, Telazol-Xylazine and Telazol-Ketamine-Xylazine as chemical restraint and anesthetic induction combination in swine. Laboratory Animal Science 43(5): 476-480.
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Thurmon, J.C. and G.J. Benson (1987). Pharmacologic consideration in selection of anesthetics for animals. Journal of the American Veterinary Medical Association191(10): 1245-1251.
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