PGE 1-induced arterial thromboresistance is a vascular property as identified by cross-perfusion technique

Abstract

Prostaglandin (PG) E 1 has been shown to improve thromboresistance. This experiment was designed to examine whether an effect on the arterial wall or the platelets is responsible for this phenomenon. Using a cross-perfusion model, the aortic and iliac artery endothelium of rabbits was removed by a balloon catheter before being perfused with blood of donor rabbits. Donor and/or receiver animals were treated with 20 μg PGE 1 or vehicle (cyclodextrin) intravenously daily for 1 week. After the last administration of PGE 1 or its vehicle, the animals were killed and native blood from a donor rabbit was recirculated (30 ml/min) via a deendothelialized segment of a receiver rabbit. The contact (C) and spread (S) platelets as well as the denuded surface covered with platelet aggregates (> 5 μm in height) were quantified by morphometry. Deposition of 111ln-oxine labeled autologous platelets was quantitatively determined per surface unit. In addition, PGI 2- and TXB 2-formation by the denuded aortic and iliac artery segments was determined. Pretreatment of receiver rabbits with PGE 1 resulted in morphometrically assessed decreased platelet adhesion and aggregation, even when the donor rabbit was vehicle-treated. A vehicle-treated receiver rabbit, in contrast, shows platelet deposition comparable to controls, even if the donor rabbit was PGE 1-pretreated. Treatment of donor animals with PGE 1 did not result in a reduction in thrombogenicity. The beneficial in vivo PGE 1 action of decreased arterial thrombogenicity is thus mediated by an effect on the vascular wall rather than on circulating platelets.