VASCULAR INJURY, REPAIR, AND RESTENOSIS AFTER PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY IN THE ATHEROSCLEROTIC RABBIT

Background Several nonatherosclerotic animal models of restenosis exis t and are used for the evaluation of the vascular response to angiopla sty-induced injury. However, few studies have evaluated the response o f an atherosclerotic vessel to angioplasty. The present study examined the radiographic, histological, immunohistochemical, and morphometric responses over time of atherosclerotic rabbit femoral arteries after percutaneous transluminal angioplasty (PTA). Methods and Results Rabbi ts (n=94) underwent arterial desiccation and were fed a hypercholester olemic diet for 3 weeks, and then PTA was performed. Arteries were obt ained before PTA and 1, 3, 5, 7, 14, and 28 days after PTA. PTA caused radial stretching of the artery, medial compression, intramural hemor rhage, injury to normal arterial segments, and dissection within the i ntima and media. Thrombus filled and cellular accumulation repaired th e dissection. Peak smooth muscle cell and macrophage DNA synthesis was noted at 3 to 5 days after angioplasty, generally at the dissection b ut also in normal sections of the artery. Adventitial injury and subse quent adventitial cellular proliferation and collagen production were observed. A rapid decrease in the radiographic minimal luminal diamete r was noted at 3 days, resulting from vascular recoil or thrombus fill ing the dissection. At 7 to 14 days, only 24% to 33% of the luminal lo ss was accounted for by an increase in the intimal area, and 22% to 28 % of the intima was neointima. Conclusions Restenosis in an atheroscle rotic artery results from a variable combination of intimal proliferat ion, vascular remodeling/wound contraction, and recoil of the normal s ection of the artery. The variability of an atherosclerotic artery to PTA injury results from variable dissection, thrombus formation, and c ellular response to injury as well as variable scar contraction and el astic recoil.