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Animal Models in Cardiovascular Research (eBook)

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2009 | 3rd ed. 2009
XXVI, 431 Seiten
Springer New York (Verlag)
978-0-387-95962-7 (ISBN)

Lese- und Medienproben

Animal Models in Cardiovascular Research - David Gross
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Interest in the humane and scientifically justifiable use of research animals has intensified since the publication of the 2nd edition of Animal Models in Cardiovascular Research. This completely revised and updated edition will provide information essential to any researcher interested in using animal models for cardiovascular research, or any research which requires normal cardiovascular function. The format and presentation will be changed to make the text more easy to read and use: (1) This edition is in outline format, for ease and utility. (2) The opening chapter includes more information on the cardiovascular effects of post-operative analgesia and will address the recognition of pain behavior in species commonly used in research settings, particularly rats and mice. (3) New edition includes reference material more useful to researchers using transgenic and naturally occurring animal models to dissect these mechanisms.



Dr. David R. Gross entered private veterinary practice after earning the DVM degree from Colorado State University in 1960. In 1974 he was awarded the PhD degree in physiology from the Ohio State University beginning a 36-year career in academics that culminated as professor and head of the Department of Veterinary Biosciences in the College of Veterinary Medicine, University of Illinois, Urbana-Champaign. Dr. Gross' research career encompassed 58 funded projects totaling over $5.5 million and 91 papers published in refereed journals using a wide variety of animal models. Ironically his three most-cited research papers received no external funding. He and his colleagues showed that feeding dietary cholesterol to rabbits induced Alzheimer's-like lesions in the brain. Their work also showed that surgery involving cardiopulmonary bypass resulted in Alzheimer's-like brain lesions in pigs. With another group of colleagues he helped pioneer minimally invasive coronary artery bypass grafting techniques using the pig as a model.


This new edition of Animal Models in Cardiovascular Research describes historical and recent advances in our understanding of the cardiovascular system from studies conducted in a variety of animal models. Since the last edition we have witnessed an explosion in the use of both congenic and transgenic animals. The use of specific knock-in and knock-out transgenic models has resulted in an avalanche of genetic, molecular and protein-based information that, potentially, could result in an amazing new array of treatment and management options. However, the results of these studies also introduce a sometime bewildering array of redundant, overlapping and competing molecular pathways involved in both physiological and pathological responses. This third edition is designed to provide a better basis for understanding and using animal models in the current climate of background knowledge and information. It is significantly different than the previous two editions. Chapter 1 is updated from the previous editions addressing general principles of animal selection. It also provides expanded tables of normal physiological values for easy reference. Chapter 2 covers preoperative care, pre-anesthesia, chemical restraint, and includes a significantly expanded section on pain recognition and analgesia particularly in rodents. Chapter 3 provides a summary of normal cardiovascular parameters obtained from intact, awake animals. The data have been rearranged in outline rather than the previous tabular form hopefully resulting in easier reference. Chapter 4 addresses the techniques, problems and pitfalls of measuring cardiac function in animals. There is an emphasis on the proper use of these measurements to develop new treatment and management strategies as well as using them to study mechanisms of disease. Chapter 5 emphasizes the techniques, problems and pitfalls involved in the measurement of arterial function and ventricular/arterial coupling dynamics. Again the emphasis is on the use of these parameters to develop new treatment and management strategies and for studying the mechanisms of disease. Chapter 6 is a all new chapter dealing specifically with the problems and pitfalls inherent in using isolated heart preparations. The need for this chapter became apparent because so much information was published using obviously non-physiologic preparations. The use of both pumping and non-pumping preparations are described along with techniques necessary for using hearts from larger species where oxygen carrying capacity of the perfusate is critical. The importance of hypoxia and anoxia in the interpretation of results is discussed. Chapter 7 focuses on the cardiovascular effects of the post-operative analgesic drugs commonly used today and how to avoid potential problems resulting from these effects when reporting experimental data. These data are also presented in outline form rather than the tabular format used in the two previous editions. Chapter 8 addresses the use of naturally occurring animal models of valvular and infectious cardiovascular disease. The information presented has been updated and expanded from the second edition. Chapter 9 examines iatrogenic models of ischemic heart disease. Chapter 10 is new. It provides a review of iatrogenic, transgenic and naturally occurring animal models of cardiomyopathy and heart failure. Chapter 11 includes new, updated and revised information reviewing iatrogenic and transgenic models of hypertension. Chapter 12 contains new, and updated information on iatrogenic and transgenic models of atherosclerotic disease. Chapter 13 is completely new material dealing with animal models for the study of neurohumeral and central nervous system control of the cardiovascular system. Chapter 14 is also new. It provides examples of cardiovascular studies involving the use of specific transgenic models not normally associated with the cardiovascular system, such as estrogen receptor knockouts, to study cardiovascular function.

Dr. David R. Gross entered private veterinary practice after earning the DVM degree from Colorado State University in 1960. In 1974 he was awarded the PhD degree in physiology from the Ohio State University beginning a 36-year career in academics that culminated as professor and head of the Department of Veterinary Biosciences in the College of Veterinary Medicine, University of Illinois, Urbana-Champaign. Dr. Gross’ research career encompassed 58 funded projects totaling over $5.5 million and 91 papers published in refereed journals using a wide variety of animal models. Ironically his three most-cited research papers received no external funding. He and his colleagues showed that feeding dietary cholesterol to rabbits induced Alzheimer’s-like lesions in the brain. Their work also showed that surgery involving cardiopulmonary bypass resulted in Alzheimer’s-like brain lesions in pigs. With another group of colleagues he helped pioneer minimally invasive coronary artery bypass grafting techniques using the pig as a model.

Preface 6
Acknowledgements 8
Introduction 9
Contents 11
About the Author 22
General Principles of Animal Selection and Normal Physiological Values 23
Special Requirement Considerations 24
Normal Physiological Data 25
References 30
Preanesthesia, Anesthesia, Chemical Restraint, and the Recognition and Treatment of Pain and Distress 38
General Principles of Pain Recognition in Animals 38
The Use of Anti-Cholinergic Drugs for Preanesthesia 42
General Comments on Preanesthetic Agents 43
Preanesthesia and Anesthesia in Rats and Mice 43
Chemical Restraint (Sedation) in Rats and Mice 44
Pain and Distress Recognition in Rats and Mice 44
Treatment of Pain in Rats and Mice 47
Preanesthesia and Anesthesia in Rabbits 49
Chemical Restraint (Sedation) in Rabbits 50
Pain Recognition in Rabbits 50
Treatment of Pain in Rabbits 50
Preanesthesia and Anesthesia in Dogs 51
Chemical Restraint (Sedation) in Dogs 53
Pain Recognition in Dogs 54
Treatment of Pain in Dogs 55
Preanesthesia and Anesthesia in Cats 56
Chemical Restraint (Sedation) in Cats 57
Pain Recognition in Cats 58
Treatment of Pain in Cats 58
Preanesthesia and Anesthesia in Guinea Pigs 59
Chemical Restraint (Sedation) in Guinea Pigs 59
Pain Recognition in Guinea Pigs 59
Treatment of Pain in Guinea Pigs 60
Preanesthesia and Anesthesia in Pigs 60
Chemical Restraint (Sedation) in Pigs 62
Pain Recognition in Pigs 62
Treatment of Pain in Pigs 62
Preanesthesia and Anesthesia in Calves, Sheep, and Goats 63
Chemical Restraint (Sedation) in Small Ruminants 64
Recognition of Pain in Small Ruminants 64
Treatment of Pain in Small Ruminants 65
Preanesthesia and Anesthesia in Rhesus Monkeys 66
Chemical Restraint (Sedation) in Rhesus Monkeys 66
Pain Recognition in Rhesus Monkeys 66
Treatment of Pain in Rhesus Monkeys 67
Conclusions 68
References 68
Normal Cardiac Function Parameters 76
References 80
Measuring Cardiac Function 86
The Pressure–Volume Relationship 88
Another Measure of Ventricular Elasticity 89
Measurement of Electrical Activity 89
Measurement of Pressure 90
Echocardiography 91
Doppler Flow Velocity and Tissue Doppler Imaging 95
Tissue Doppler Imaging 97
Examples of Ultrasound Data Reported Using < 20-MHz Transducers
Examples of Ultrasound Data Reported Using 20-MHz ( or Greater) Transducers 99
Summary of Information Needed to Ascertain the Reliability of Ultrasound Data 101
Techniques for Measuring Ventricular Volumes 101
Other Measures of Myocardial Physical Properties 105
Measuring Diastolic Dysfunction 107
References 108
Measuring Vascular Function and Ventricular/ Arterial Coupling Dynamics 113
History 113
Quantification of Arterial Compliance 114
Force-Displacement Measurements 115
Pulse Wave Velocity 117
Modeling Techniques for Estimating Vascular Mechanical Behavior 119
Ventricular/Vascular Coupling 121
Tissue Doppler Imaging and Elasticity Imaging 124
References 125
Isolated Heart Preparations, Problems, and Pitfalls 129
Development of the Isolated Heart Preparation 129
Retrograde Perfusion Preparations ( The Langendorff Preparation) 132
Choosing between the Pressure-Regulated or Flow-Regulated Langendorff- Type Preparation 134
The Isolated, Working, In Situ Heart-Lung Preparation 134
The Isolated Working Left Heart Preparation 134
The Langendorff-Type Perfused Working Left Heart Preparation 135
The Biventricular Isolated Working Heart Preparation 137
The Biventricular, Retrograde-Perfused, Working Heart Preparation 139
Perfusion Solutions 140
Support Animals 142
Washed Red Blood Cell Addition to the Perfusate 142
Problems and Pitfalls 143
Heterotopic Transplants 146
References 147
Cardiovascular Effects of Anesthetics, Sedatives, Postoperative Analgesic Agents, and Other Pharmaceuticals 151
Barbiturates 151
Propofol 152
a -Chloralose 153
Urethane 154
a -Chloralose + Urethane 154
Steroid Anesthetic Agents 154
Inhalation Anesthetic Agents 155
The Opioids 161
Dissociative Anesthetic Agents 170
Imidazole and Other Hypnotic, Amnesiac, Anxiolytic, or Antipsychotic Compounds 172
a-2 Adrenergic Receptor Agonists 176
a-2-Adrenergic Receptor Agonists 177
Rauwolfia Derivatives 178
Phenothiazine Derivatives 180
Other Phenothiazine Derivatives 183
Butyrophenones 184
Other Antipsychotic/Anxiolytic/Antidepressant ( Tranquilizer) Drugs 186
Atypical Antipsychotics 189
Atypical Antipsychotics 191
Drugs in Combination Providing Neurolept Analgesia/ Anesthesia 192
Local Anesthetic Agents 202
Non-steroidal Anti-inflammatory Agents 203
Neuromuscular Blocking Agents 205
Aminoglycoside, Fluoroquinolone, and Anthracycline Antibiotics 207
References 207
Naturally Occurring and Iatrogenic Animal Models of Valvular, Infectious, and Arrhythmic Cardiovascular Disease 222
Congenital Cardiac Defects, General Information 222
Genetically Engineered Models, General Information 223
Naturally Occurring Models of Valvular Disease 224
Iatrogenic Models of Valvular Disease 226
Infectious Cardiovascular Disease 227
Diphtheritic Myocarditis 228
Encephalomyocarditis Virus 229
Autoimmune Myocarditis 229
Arrhythmic Cardiovascular Disease 230
References 233
Iatrogenic Models of Ischemic Heart Disease 238
Global Ischemia 238
Regional Ischemia 240
References 245
Iatrogenic, Transgenic, and Naturally Occurring Models of Cardiomyopathy and Heart Failure 249
Naturally Occurring Models of Cardiomyopathy 250
Iatrogenic Models of Cardiomyopathy and Heart Failure 253
Other Iatrogenic Models of Cardiomyopathy and Heart Failure 255
Transgenic Models of Cardiomyopathy and Heart Failure 259
References 264
Iatrogenic, Congenic, and Transgenic Models of Hypertension 276
Renovascular Hypertension 277
Genetic Models of Hypertension 283
Dahl Salt-Sensitive and Insensitive Rats 287
Angiotensin-II-Induced Hypertension 290
DOCA-Induced Hypertension 293
NO-Synthesis Blockade Hypertension 295
Glucocorticoid-Induced Hypertension 297
Intrauterine Growth-Restricted Induced Hypertension 298
Other Transgenic and Congenic Models of Hypertension 300
Other Models of Systemic Hypertension 308
Pulmonary Hypertension 309
References 311
Naturally Occurring, Iatrogenic and Transgenic Models of Atherosclerotic Disease 323
Characteristics of Plaque Rupture and Resulting Thrombosis 325
Implication of New “Players” in the Pathogenesis of Atherosclerotic Disease 325
Animal Models 326
Graft Vasculopathy 339
Hamsters 340
Sand Rats 340
References 340
Animal Models for the Study of Neurohumeral and Central Neural Control of the Cardiovascular System 346
The Autonomic Nervous System in Blood Pressure Homeostasis and Cardiorespiratory Reflex Responses 348
Rostal and Caudal Ventrolateral Medulla 349
Nucleus Tractus Solitarius 352
Hypothalamic Paraventricular Nucleus 354
Periaqueductal Gray 355
Anterior and Posterior Hypothalamic Areas 357
Median Preoptic Nucleus 357
Nucleus Cuneatus 357
Lateral Parabrachial Nucleus and the Dorsal Raphe Nucleus 358
Caudal Vestibular Nucleus 358
Gender Effects on Central Control of Cardiovascular Responses 358
Neurohumeral Control 359
References 363
Other Transgenic Animal Models Used in Cardiovascular Studies 370
Sex-Related Responses 371
Kinases 372
Oxidases and Oxygenases 373
Adenosine and Adrenergic Receptors 374
Nitric Oxide Synthase 375
Metabolic Syndrome 376
Xenotransplantation 377
Na + /Ca 2+ and Na + /H + Exchangers 379
Inflammatory Cytokines 380
Peroxisome Proliferator-Activated Receptor 381
Renin-Angiotensin System 381
Bradykinin-2 Receptor 382
Apolipoprotein-E and Low-Density Lipoprotein Knockout Models 382
Toll-Like Receptors 383
Caveolin-1 (Cav-1) 383
Long QT Syndrome 384
Nuclear Factor Kappa-B 384
Orphan Nuclear Receptors 385
Troponin 385
Chromogranin A 386
Lectin-Like Oxidized Low-Density Lipoprotein Receptor 386
Junctin 386
Connexin 387
Phospholamban 387
Fas Ligand 388
Proteases, Metalloproteinases, and ATPases 388
Binary Calsequestrin/P2Xr-Purinergic Receptor ( CSQ/ P2X4R) Transgenics 389
pro-ANP Gene Disrupted Mouse 390
Macrophage Colony-Stimulating Factor 390
Endothelin-1 390
Elastin 391
a-2-Antiplasmin 391
cAMP Response Element Binding Protein 391
Fatty Acid Transport Protein: CD36 391
Clotting Factor XIII 392
Apelin 392
T-Box Transcription Factor 392
Thrombospondin-1 and Its Receptor CD47 392
Polyomavirus Middle T Antigen 393
Thrombopoietin Receptor 393
Vascular Endothelial Growth Factor 393
Osteopontin 393
ATP-Binding Membrane Cassette Transporter-A1 394
The K + /Cl Cotransporter KCC3 394
Aldosterone Synthase Overexpression 394
Cysteine and Glycine-Rich Protein-2 (CSRP-2) 394
Parathyroid Hormone Type-1 Receptor and PTH/ PTH- Related Protein 395
Vitamin D Receptor 395
Thromboxane Receptor (Tp) 395
T and B Cells 395
Vanilloid Type-1 Receptors (TRPV-1) 396
Serotonin Transporter (SERT) 396
CC Chemokine Receptor-2 (CCR-2) 396
Thymosin b -4 396
References 397
Index 408

Erscheint lt. Verlag 26.6.2009
Zusatzinfo XXVI, 431 p.
Verlagsort New York
Sprache englisch
Themenwelt Medizin / Pharmazie Medizinische Fachgebiete Chirurgie
Medizinische Fachgebiete Innere Medizin Kardiologie / Angiologie
Naturwissenschaften Biologie Zoologie
Technik
Schlagworte animal • cardiac function • Cardiovascular • cardiovascular function • Dynamics • Gross • Hypertension • Models • nervous system • Research
ISBN-10 0-387-95962-9 / 0387959629
ISBN-13 978-0-387-95962-7 / 9780387959627
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