Antiplatelet therapy reduces aortic intimal hyperplasia distal to small diameter vascular prostheses (PTFE) in nonhuman primates.

Abstract

While the use of prosthetic grafts in small diameter arterial reconstruction is required when suitable autogenous graft material is unavailable, late occlusion of prosthetic grafts caused by proliferative lesions has been described. This study evaluated the suitability of 3-mm (ID) microporous polytetrafluoroethylene (PTFE) Gore-Tex grafts inserted in the abdominal aorta of eight nonhuman primates (Macaca fascicularis), and the effects of prolonged antiplatelet treatment on both graft patency and the development of intimal hyperplasia in the adjacent vasculature. Four monkeys received antiplatelet medication consisting of aspirin (163 mg twice daily) and dipyridamole (25 mg twice daily). When killed at four months following graft insertion, all four grafts in the antiplatelet medicated group were patent, while in the control group, only two of four grafts were patent. Histologic examination and quantitative photogravitometric evaluation of the degree of luminal narrowing were performed on all grafts and the adjacent vasculature. These studies revealed that while all graft and aortic segments showed varying amounts of intimal thickening, occlusions in the control animals were related to intimal hyperplasia in the host aorta at the site of the distal anastomosis. Intimal hyperplasia in all aortic segments examined distal to the graft was significantly reduced by antiplatelet therapy. Electronmicroscopy showed that smooth muscle cells were the predominant cells of the intimal thickening of the aorta (intimal hyperplasia), and that proliferation of these cells did not extend into the graft itself. The predominant cell population of the intimal thickening of the graft were of the myofibroblast type (neointimal hyperplasis). The luminal surface of the graft was lined with cells that had some but not all of the characteristics of mature endothelial cells. In vitro studies confirmed global interference with platelet function and arachidonic acid metabolism in medicated animals. Medication inhibited platelet cyclo-oxygenase without affecting platelet lipoxygenase, thromboxane synthetase, or prostacyclin-like activity in undisturbed arteries. This study shows that severe intimal hyperplasia develops rapidly in the recipient vessel adjacent to small diameter Gore-Tex grafts, and that the severity of the response is reduced by antiplatelet agents. Histologic examination revealed that the intimal thickening in the graft and the adjacent aortic segments were composed of cells that were not morphologically identical, suggesting two separate aetiologies and the possible need to use different approaches in their prevention.