INHIBITOR OF ANGIOTENSIN-CONVERTING ENZYME MODIFIES MYOINTIMAL ORIGININ AN ARTERIAL AUTOGRAFT MODEL

Pharmacologic modulation by an inhibitor of angiotensin-converting enz yme (IACE: cilazapril) of vascular proliferative response to a full-th ickness arterial injury (autograft) was studied in rats. An arterial a utograft 5 mm long was made in the right common iliac artery of 50 fem ale Sprague-Dawley rats (weight 250-300 g) by microsurgical techniques . The animals were divided into two study groups: group I (controls), 20 animals that underwent arterial autograft but received no other tre atment; and group II (cilazapril-treated), 20 rats that underwent arte rial autograft and received cilazapril (Roche), 10 mg/day orally (p.o. ) in an excipient of 2% arabic gum, for 4 days before operation. Anima ls were killed on postoperative days 7, 14, 21, 30, and 50, and grafts were studied by light microscopy, scanning and transmission electron microscopy, and morphometry. In the control group, the hyperplasic res ponse had begun by postoperative day 14 and was established by postope rative day 50, In the medial layer, the muscle cells changed in phenot ype from contractile to secretory cells. The adventitia had a highly p roliferative appearance. In the cilazapril-treated group, fibrin depos its and platelets formed a layer on the internal elastic lamina. This layer appeared to evolve toward an intimal hyperplasia that became qua ntifiable by postoperative day 21. The medial layer was clearly thinne d and showed intense accumulation of lipid microvacuoles, elastic dege neration, and vacuolized cells. Our results suggest that the use of an inhibitor of ACE modified the origin of the intimal hyperplasia in th e arterial autograft model. Enhancement of the thrombogenicity of the luminal surface favors myointimal development by thrombus reorganizati on.