PGE1-induced arterial thromboresistance is a vascular property as identified by cross-perfusion technique

Prostaglandin (PG) E1 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 microg PGE1 or vehicle (cyclodextrin) intravenously daily for 1 week. After the last administration of PGE1 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 microm in height) were quantified by morphometry. Deposition of (111)In-oxine labeled autologous platelets was quantitatively determined per surface unit. In addition, PGI(2)- and TXB2-formation by the denuded aortic and iliac artery segments was determined. Pretreatment of receiver rabbits with PGE1 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 PGE1-pretreated. Treatment of donor animals with PGE1 did not result in a reduction in thrombogenicity. The beneficial in vivo PGE1 action of decreased arterial thrombogenicity is thus mediated by an effect on the vascular wall rather than on circulating platelets.