Translational physiology: porcine models of human coronary artery disease: implications for preclinical trials of therapeutic angiogenesis.

"Therapeutic angiogenesis" describes an emerging field of cardiovascular medicine whereby new blood vessels are induced to grow to supply oxygen and nutrients to ischemic cardiac or skeletal muscle. Various methods of producing therapeutic angiogenesis have been employed, including mechanical means, gene therapy, and the use of growth factors, among others. The use of appropriate large-animal models is essential if these therapies are to be critically evaluated in a preclinical setting before their use in humans, yet little has been written comparing the various available models. Over the past decade, swine have been increasingly used in studies of chronic ischemia because of their numerous similarities to humans, including minimal preexisting coronary collaterals as well as similar coronary anatomy and physiology. Consequently, this review describes the most commonly used swine models of chronic myocardial ischemia with special attention to regional myocardial blood flow and function and critically evaluates the strengths and weaknesses of each model in terms of utility for preclinical trials of angiogenic therapies.

[1]  D. Yellon,et al.  Species variation in the coronary collateral circulation during regional myocardial ischaemia: a critical determinant of the rate of evolution and extent of myocardial infarction. , 1987, Cardiovascular research.

[2]  J. Isner,et al.  Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. , 1999, Circulation research.

[3]  M. Leschke,et al.  Refractory angina pectoris in end-stage coronary artery disease: evolving therapeutic concepts. , 1997, American heart journal.

[4]  H C Hughes,et al.  Swine in cardiovascular research. , 1986, Laboratory animal science.

[5]  O. Rimoldi,et al.  Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans. , 2001, Cardiovascular research.

[6]  Hughes Gc Cellular models of hibernating myocardium: implications for future research. , 2001 .

[7]  J. Isner,et al.  Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. , 1999, The Annals of thoracic surgery.

[8]  J D Pearlman,et al.  Therapeutic angiogenesis with basic fibroblast growth factor: technique and early results. , 1998, The Annals of thoracic surgery.

[9]  R. Coleman,et al.  Is chronically dysfunctional yet viable myocardium distal to a severe coronary stenosis hypoperfused? , 2001, The Annals of thoracic surgery.

[10]  S. Vatner,et al.  Inotropic reserve and histological appearance of hibernating myocardium in conscious pigs with ameroid-induced coronary stenosis , 1996, Basic Research in Cardiology.

[11]  W. Schaper Quo vadis collateral blood flow? A commentary on a highly cited paper. , 2000, Cardiovascular research.

[12]  A. Vineberg,et al.  The experimental production of coronary artery insufficiency and occlusion. , 1957, American heart journal.

[13]  J. Longhurst,et al.  Chronic Reduction of Myocardial Ischemia Does Not Attenuate Coronary Collateral Development in Miniswine , 1992, Circulation.

[14]  J. Vanoverschelde,et al.  The pathophysiology of myocardial hibernation: current controversies and future directions. , 2001, Progress in cardiovascular diseases.

[15]  H. Spotnitz,et al.  Validation study of a new transit time ultrasonic flow probe for continuous great vessel measurements. , 1996, ASAIO journal.

[16]  J. Pearlman,et al.  Intrapericardial delivery of fibroblast growth factor-2 induces neovascularization in a porcine model of chronic myocardial ischemia. , 2000, The Journal of pharmacology and experimental therapeutics.

[17]  W. Schaper,et al.  A self-perpetuating vicious cycle of tissue damage in human hibernating myocardium , 2000, Molecular and Cellular Biochemistry.

[18]  M. Codd,et al.  Correlation of myocardial histologic changes in hibernating myocardium with dobutamine stress echocardiographic findings. , 1998, American heart journal.

[19]  R. Millard,et al.  Induction of functional coronary collaterals in the swine heart , 1981, Basic Research in Cardiology.

[20]  R. Coleman,et al.  Neovascularization after transmyocardial laser revascularization in a model of chronic ischemia. , 1998, The Annals of thoracic surgery.

[21]  J. Lowe,et al.  Metabolic Changes in the Normal and Hypoxic Neonatal Myocardium , 1999, Annals of the New York Academy of Sciences.

[22]  L. Cohn,et al.  Complete reversal of ischemic wall motion abnormalities by combined use of gene therapy with transmyocardial laser revascularization. , 1998, The Journal of thoracic and cardiovascular surgery.

[23]  F. Sellke,et al.  Therapeutic angiogenesis for coronary artery disease , 2002, Current treatment options in cardiovascular medicine.

[24]  R. B. Coleman,et al.  Intermediate-term clinical outcome following transmyocardial laser revascularization in patients with refractory angina pectoris. , 1999, Circulation.

[25]  W. Schaper,et al.  Generation and localisation of monoclonal antibodies against fibroblast growth factors in ischaemic collateralised porcine myocardium. , 1993, Cardiovascular research.

[26]  G. Schulz,et al.  Prolonged myocardial hibernation exacerbates cardiomyocyte degeneration and impairs recovery of function after revascularization. , 1998, Journal of the American College of Cardiology.

[27]  F. C. White,et al.  Coronary collateral circulation in the pig: correlation of collateral flow with coronary bed size , 1981, Basic Research in Cardiology.

[28]  W. Baumgartner,et al.  Anatomic and anesthetic considerations in experimental cardiopulmonary surgery in swine. , 1986, Laboratory animal science.

[29]  J. Vanoverschelde,et al.  Glucose for the heart. , 1999, Circulation.

[30]  J I Hoffman,et al.  Blood flow measurements with radionuclide-labeled particles. , 1977, Progress in cardiovascular diseases.

[31]  W. Elzinga Ameroid constrictor: uniform closure rates and a calibration procedure. , 1969, Journal of applied physiology.

[32]  R. Coleman,et al.  Induction of angiogenesis after TMR: a comparison of holmium: YAG, CO2, and excimer lasers. , 2000, The Annals of thoracic surgery.

[33]  S. Vatner,et al.  Mechanism of impaired myocardial function during progressive coronary stenosis in conscious pigs. Hibernation versus stunning? , 1995, Circulation research.

[34]  F. Peale,et al.  Gene profiling techniques and their application in angiogenesis and vascular development , 2001, The Journal of pathology.

[35]  R. Coleman,et al.  A comparison of mechanical and laser transmyocardial revascularization for induction of angiogenesis and arteriogenesis in chronically ischemic myocardium. , 2002, Journal of the American College of Cardiology.

[36]  W. Schaper,et al.  Molecular mechanisms of coronary collateral vessel growth. , 1996, Circulation research.

[37]  D. Waters,et al.  Reversibility and pathohistological basis of left ventricular remodeling in hibernating myocardium. , 2000, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[38]  R. Coleman,et al.  Improved perfusion and contractile reserve after transmyocardial laser revascularization in a model of hibernating myocardium. , 1999, The Annals of thoracic surgery.

[39]  R. Crystal,et al.  Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. , 1998, The Journal of thoracic and cardiovascular surgery.

[40]  Deepak L. Bhatt,et al.  Direct myocardial revascularization and angiogenesis--how many patients might be eligible? , 1999, The American journal of cardiology.

[41]  R. Phillips,et al.  The Yucatan miniature pig: characterization and utilization in biomedical research. , 1986, Laboratory animal science.

[42]  C. Bloor,et al.  The pig as a model for myocardial ischemia and exercise. , 1986, Laboratory animal science.

[43]  W. Zoghbi,et al.  Dobutamine echocardiography in myocardial hibernation. Optimal dose and accuracy in predicting recovery of ventricular function after coronary angioplasty. , 1995, Circulation.

[44]  P. Pagel,et al.  Temporal dependence of coronary collateral development. , 1997, Cardiovascular research.

[45]  D. Waters,et al.  Myocardial cell death and apoptosis in hibernating myocardium. , 1997, Journal of the American College of Cardiology.

[46]  A. Liedtke,et al.  An animal model of chronic coronary stenosis resulting in hibernating myocardium. , 1992, The American journal of physiology.

[47]  J. Longhurst,et al.  Development of coronary collateral circulation in left circumflex Ameroid-occluded swine myocardium. , 1987, The American journal of physiology.

[48]  R. deKemp,et al.  Delay in revascularization is associated with increased mortality rate in patients with severe left ventricular dysfunction and viable myocardium on fluorine 18-fluorodeoxyglucose positron emission tomography imaging. , 1998, Circulation.

[49]  D. Waters,et al.  Functional and structural alterations with 24-hour myocardial hibernation and recovery after reperfusion. A pig model of myocardial hibernation. , 1996, Circulation.

[50]  N. Weissman,et al.  Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia. , 2001, Journal of the American College of Cardiology.

[51]  J. Longhurst,et al.  Effect of long-term exercise on regional myocardial function and coronary collateral development after gradual coronary artery occlusion in pigs. , 1990, Circulation.

[52]  J. Pearlman,et al.  Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia. , 2000, The Annals of thoracic surgery.

[53]  Dobutamine Stress Echocardiography Identifies Hibernating Myocardium and Predicts Recovery of Left Ventricular Function after Coronary Revascularization , 1993 .

[54]  M. Simons,et al.  Therapeutic coronary angiogenesis: a fronte praecipitium a tergo lupi? , 2001, American journal of physiology. Heart and circulatory physiology.

[55]  C M Bloor,et al.  Coronary collateral development in swine after coronary artery occlusion. , 1992, Circulation research.

[56]  D. Warltier,et al.  Repetitive coronary artery occlusions induce release of growth factors into the myocardial interstitium. , 1998, American journal of physiology. Heart and circulatory physiology.

[57]  A. Deussen,et al.  Coronary reserve of high- and low-flow regions in the dog heart left ventricle. , 1998, Circulation.

[58]  J. Canty,et al.  Differential 18F-2-deoxyglucose uptake in viable dysfunctional myocardium with normal resting perfusion: evidence for chronic stunning in pigs. , 1999, Circulation.

[59]  I. Buschmann,et al.  Arteriogenesis, the good and bad of it. , 1999, European heart journal.

[60]  W Schaper,et al.  The development of collateral circulation in the pig and dog heart. , 1967, Cardiologia.

[61]  D. Hearse,et al.  The elusive coypu: the importance of collateral flow and the search for an alternative to the dog , 2000 .

[62]  J. Lowe,et al.  Transmyocardial laser revascularization: experimental and clinical results. , 1999, The Canadian journal of cardiology.

[63]  I. Herman,et al.  Mechanisms of normal and tumor-derived angiogenesis. , 2002, American journal of physiology. Cell physiology.

[64]  D. Levin Pathways and Functional Significance of the Coronary Collateral Circulation , 1974, Circulation.

[65]  A newly developed X-ray transparent ameroid constrictor for study on progression of gradual coronary stenosis , 1980, Basic Research in Cardiology.

[66]  Gil Vm Hibernating myocardium. An incomplete adaptation to ischemia , 1998 .

[67]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[68]  E. Unger,et al.  Experimental evaluation of coronary collateral development. , 2001, Cardiovascular research.

[69]  A. S. Greene Application of Physiological Genomics to the Microcirculation , 2002, Microcirculation.

[70]  R. B. Johnson,et al.  Efficacy of intracoronary or intravenous VEGF165 in a pig model of chronic myocardial ischemia. , 2001, Journal of the American College of Cardiology.

[71]  T. Turkington,et al.  Estimation of myocardial blood flow for longitudinal studies with 13N-labeled ammonia and positron emission tomography , 1996, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[72]  L. Opie,et al.  Myocardial metabolism in ischemic heart disease: basic principles and application to imaging by positron emission tomography. , 1989, Progress in cardiovascular diseases.

[73]  L. Opie The multifarious spectrum of ischemic left ventricular dysfunction: relevance of new ischemic syndromes. , 1996, Journal of molecular and cellular cardiology.

[74]  Hughes Hc,et al.  Swine in cardiovascular research. , 1986 .

[75]  J. Longhurst,et al.  Ameroid constriction of the proximal left circumflex coronary artery in swine. A model of limited coronary collateral circulation. , 1987, The American journal of cardiovascular pathology.

[76]  D. Warltier,et al.  Ischemia-Induced Coronary Collateral Growth Is Dependent on Vascular Endothelial Growth Factor and Nitric Oxide , 2000, Circulation.

[77]  D. Duncker,et al.  Animal models in the study of myocardial ischaemia and ischaemic syndromes. , 1998, Cardiovascular research.

[78]  L. Smith,et al.  General anesthetic techniques in swine. , 1996, The Veterinary clinics of North America. Food animal practice.

[79]  R. Coleman,et al.  An experimental model of chronic myocardial hibernation. , 2000, The Annals of thoracic surgery.

[80]  F. Sellke,et al.  Therapeutic angiogenesis in cardiology using protein formulations. , 2001, Cardiovascular research.

[81]  Diao Mf Predicting improved function after myocardial revascularization. , 1998 .

[82]  R Greene,et al.  Left ventricular functional improvement after transmyocardial laser revascularization. , 1998, The Annals of thoracic surgery.

[83]  J. Canty,et al.  18F-2-deoxyglucose deposition and regional flow in pigs with chronically dysfunctional myocardium. Evidence for transmural variations in chronic hibernating myocardium. , 1997, Circulation.

[84]  A. Vineberg,et al.  Experimental gradual coronary artery constriction by ameroid constrictors. , 1960, Surgery.

[85]  C. Degueldre,et al.  Relation between contractile reserve and positron emission tomographic patterns of perfusion and glucose utilization in chronic ischemic left ventricular dysfunction: implications for identification of myocardial viability. , 1997, Journal of the American College of Cardiology.

[86]  W. Schaper,et al.  Microvascular and collateral adaptation in swine hearts following progressive coronary artery stenosis , 1989, Basic Research in Cardiology.

[87]  G. C. Hughes Cellular models of hibernating myocardium: implications for future research. , 2001, Cardiovascular research.

[88]  N. A. Dame,et al.  Ultrasonic assessment of internal thoracic artery graft flow in the revascularized heart. , 1994, The Annals of thoracic surgery.