Abstract
Recurrent atherosclerotic plaque growth, restenosis. continues to be a significant problem, severely limiting the usefulness of interventions such as balloon angioplasty. Percutaneous angioplasty is designed to open narrowed or occluded arteries that cause acute heart attacks, but 30-50% of angioplasty vessels reocclude within 6 months. In this paper we review the animal models of atherosclerosis and restenosis. None of the models currently in use is entirely acceptable or accurate for the study of new therapeutic approaches to the treatment of restenosis. In this review we discuss the basis of native and induced atherosclerosis for each animal model and the success rate for each model in the prediction of clinical efficacy is then examined. The issues of single versus multiple arterial injury models as well as coronary versus peripheral arterial models are also examined. We also address the potential use of in vitro organ and cell coculture testing of new anti-restenosis agents. We have concluded after this extensive review that there is no animal model system with proven predictive accuracy in testing new agents. Further, the use of multiple injury models versus single injury models is not established. The swine and nonhuman primate models have the highest predictive accuracy, but the primate model has many inherent difficulties. The rat, rabbit, and avian models have selective use for assessment of new pharmaceutical agents and interventional devices. Final analysis of any agent as a treatment for restenosis requires clinical testing for a assessment of efficacy.