GEOMETRIC REMODELING IS NOT THE PRINCIPAL PATHOGENETIC PROCESS IN RESTENOSIS AFTER BALLOON ANGIOPLASTY - EVIDENCE FROM CORRELATIVE ANGIOGRAPHIC-HISTOMORPHOMETRIC STUDIES OF ATHEROSCLEROTIC ARTERIES IN RABBITS

Background Restenosis after balloon angioplasty of coronary arteries i s thought to be a proliferative response of the arterial wall to injur y. Recently, it has been suggested that geometric remodeling of the ar terial wall, rather than intimal fibromuscular hyperplasia, may be the major pathophysiological mechanism underlying restenosis. In this stu dy, we evaluated the relative contribution of a geometric decrease in arterial size versus neointimal growth to luminal narrowing associated with restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits. Methods and Results Focal femoral atherosclerosis was induced by endothelial desiccation injury followed by a 2% choles terol diet. After 1 month on the high cholesterol diet, the animals we re subjected to one of four strategies: (1) balloon angioplasty, (2) b alloon angioplasty followed by treatment with the factor Xa inhibitor antistasin, (3) combined laser and balloon angioplasty, or (4) no angi oplasty. Animals were killed 2 hours or 28 days after angioplasty, and excised femoral artery segments were prepared for histomorphometric a nalysis. Angiography was performed serially before and immediately aft er angioplasty and before the animals were killed. An initial postproc edural gain in luminal diameter at sites of angioplasty was followed b y a significant reduction in diameter by angiography and a significant increase in luminal cross-sectional area narrowing by plaque by histo morphometry 28 days after angioplasty compared to adjacent nonangiopla stied segments of the same arteries, to nonangioplastied control arter ies, or to angioplastied segments of animals treated with the factor X a inhibitor antistasin. By contrast, the overall arterial size (cross- sectional area bounded by the external elastic lamina) at sites of res tenosis was not significantly different from adjacent nonangioplastied segments in the majority of arteries excised at 28 days, and the mean overall arterial size at sites of restenosis was not significantly di fferent from corresponding segments of nonangioplastied control arteri es or from angioplastied segments of animals treated with antistasin. In the minority of angioplastied arteries in which the arterial size d id change, most got larger. Conclusions Geometric remodeling resulting in a decrease in overall cross-sectional arterial size does not appea r to be the principal pathogenetic mechanism for restenosis after ball oon angioplasty with or without laser in this experimental model.