Pigs, Dogs, Baboons, and Man: Lessons for Stenting from Animal Studies

A new era in interventional cardiology has arrived with the widespread use of intracoronary stents. These devices have not only markedly improved the safety of dilatation, but have also limited restenosis through achievement of a larger postprocedure lumen. Much work remains in furthering this technology, since two major limitations are thrombosis and neointimal hyperplasia that still cause restenosis. Stent placement in animals provides insight into both of these areas. The volume of neointima is directly proportional to the depth of injury induced by the stent in at least three species: the pig, baboon, and dog. Across each species, a numerically different slope exists for the injury-neointimal thickness regression. Treatments to limit hyperplasia within a species do not change this slope, but instead alter the y-intercept. Stent thrombosis in animal models consists principally of platelet-rich thrombi. The time course of thrombus appears to differ across pigs and baboons. Antiplatelet agents limit, but do not eliminate the problem in animals, suggesting that newer and more potent antiplatelet agents may improve scent thrombosis in clinical trials. The future of stent technology lies in developing an antithrombotic device that also eliminates neointimal hyperplasia. Intense studies of animal models and improved understanding of their pathophysiology will facilitate this progress.

[1]  K. Robinson,et al.  Intra-arterial stenting in the atherosclerotic rabbit. , 1988, Circulation.

[2]  R. Mason,et al.  Some species differences in fibrinolysis and blood coagulation. , 1971, Journal of biomedical materials research.

[3]  W. Edwards,et al.  Restenosis after balloon angioplasty. A practical proliferative model in porcine coronary arteries. , 1990, Circulation.

[4]  W. Roberts,et al.  Effectiveness of Recombinant Desulphatohirudin in Reducing Restenosis After Balloon Angioplasty of Atherosclerotic Femoral Arteries in Rabbits , 1991, Circulation.

[5]  K. Robinson,et al.  Coronary intimal proliferation after balloon injury and stenting in swine: an animal model of restenosis. , 1992, Journal of the American College of Cardiology.

[6]  M. Leon,et al.  Management of restenosis within the Palmaz-Schatz coronary stent (the U.S. multicenter experience. The U.S. Palmaz-Schatz Stent Investigators. , 1993, The American journal of cardiology.

[7]  J. Gavin,et al.  The intima of human coronary arteries. , 1989, American heart journal.

[8]  M. Reidy,et al.  Mechanisms of stenosis after arterial injury. , 1983, Laboratory investigation; a journal of technical methods and pathology.

[9]  C M Gibson,et al.  Generalized model of restenosis after conventional balloon angioplasty, stenting and directional atherectomy. , 1993, Journal of the American College of Cardiology.

[10]  F Joffre,et al.  Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. , 1987, The New England journal of medicine.

[11]  Sim Fh The internal elastic lamina in normal and abnormal human arteries. A barrier to the diffusion of macromolecules from the lumen. , 1989 .

[12]  K. Bailey,et al.  Effect of external beam irradiation on neointimal hyperplasia after experimental coronary artery injury. , 1992, Journal of the American College of Cardiology.

[13]  S. King,et al.  Intravascular stents, intimal proliferation and restenosis. , 1992, Journal of the American College of Cardiology.

[14]  G. Schuler,et al.  Regular Physical Exercise and Low‐Fat Diet: Effects on Progression of Coronary Artery Disease , 1992, Circulation.

[15]  K. Bailey,et al.  Coronary restenosis: prospects for solution and new perspectives from a porcine model. , 1993, Mayo Clinic proceedings.

[16]  V. Fuster,et al.  Platelet inhibitor therapy. Agents and clinical implications. , 1990, Hematology/oncology clinics of North America.

[17]  E. Gang,et al.  High dose oral amiodarone loading: electrophysiologic effects and clinical tolerance. , 1992, Journal of the American College of Cardiology.

[18]  J. Stauffer,et al.  Long-term follow-up of the first 56 patients treated with intracoronary self-expanding stents (the Lausanne experience). , 1991, The American journal of cardiology.

[19]  J. Badimón,et al.  The porcine model for the understanding of thrombogenesis and atherogenesis. , 1991, Mayo Clinic proceedings.

[20]  R A Schatz,et al.  Clinical experience with the Palmaz-Schatz coronary stent. , 1991, Journal of the American College of Cardiology.

[21]  K. Robinson,et al.  Early and late results of intracoronary arterial stenting after coronary angioplasty in dogs. , 1987, Circulation.

[22]  R E Vlietstra,et al.  Percutaneous Polymeric Stents in Porcine Coronary Arteries: Initial Experience With Polyethylene Terephthalate Stents , 1992, Circulation.

[23]  R A Schatz,et al.  Balloon-expandable intracoronary stents in the adult dog. , 1987, Circulation.

[24]  D. E. Smith,et al.  Anticoagulant effects of the selective factor XA inhibitors tick anticoagulant peptide and antistasin in the APTT assay are determined by the relative rate of prothrombinase inhibition. , 1991, Thrombosis research.

[25]  C. Dunwiddie,et al.  Comparison of the In Vivo Anticoagulant Properties of Standard Heparin and the Highly Selective Factor Xa Inhibitors Antistasin and Tick Anticoagulant Peptide (TAP) in a Rabbit Model of Venous Thrombosis , 1991, Thrombosis and Haemostasis.

[26]  R E Vlietstra,et al.  Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. , 1992, Journal of the American College of Cardiology.

[27]  R. Erbel,et al.  Coronary stent implantation in acute vessel closure 48 hours after an unsatisfactory coronary angioplasty. , 1990, Catheterization and cardiovascular diagnosis.

[28]  V. Fuster,et al.  Importance of antithrombin therapy during coronary angioplasty. , 1991, Journal of the American College of Cardiology.

[29]  S. Schwartz,et al.  Endothelial regeneration. V. Inhibition of endothelial regrowth in arteries of rat and rabbit. , 1983, Laboratory investigation; a journal of technical methods and pathology.

[30]  Sim Fh Discontinuities in the internal elastic lamina: a comparison of coronary and internal mammary arteries , 1985 .

[31]  A. Colombo,et al.  Coronary stenting: single institution experience with the initial 100 cases using the Palmaz-Schatz stent. , 1992, Catheterization and cardiovascular diagnosis.

[32]  P. Serruys,et al.  Restenosis after coronary angioplasty: the paradox of increased lumen diameter and restenosis. , 1992, Journal of the American College of Cardiology.

[33]  E J Topol,et al.  The restenosis paradigm revisited: an alternative proposal for cellular mechanisms. , 1992, Journal of the American College of Cardiology.

[34]  R A Schatz,et al.  Introduction to intravascular stents. , 1988, Cardiology clinics.

[35]  W J Penny,et al.  Hirudin, heparin, and placebo during deep arterial injury in the pig. The in vivo role of thrombin in platelet-mediated thrombosis. , 1990, Circulation.