Clinical Use of Prostacyclin in Vascular Disease

Abstract

Two main biological effects of prostacyclin, i.e., its effect on platelets and vasodilation, were already observed during the first intravenous administration of prostacyclin to man [5, 25] and were confirmed in later studies [7, 14]. The action of pros-tacyclin on platelets is manifested in its anti-aggregatory and disaggregatory properties [5, 18, 26]. The former are seen as a marked inhibition of ADP- or collagen-induced platelet aggregation in PRP, the latter as dispersion of both circulating platelet aggregates and platelet thrombi that have been formed on a collagen surface [18]. These effects are observed within first 15–45 min of infusion of prostacyclin (PGI2). However, after 24 hr, and usually after 72 hr of administration of PGI2, an unexpected activation of platelets is observed in patients who were treated with prostacyclin (2–5 ng/kg/min i.v.) (Fig. 1). Recently, Sinzinger et al. [16]. found in vivo a similar activation of platelets in patients with peripheral arterial disease who were treated with PGI2 (5 ng/kg/min) for a period of 8 days. A sudden decrease in platelet sensitivity to PGI2, increased β-thromboglobulin level in blood, increased circulating platelet factor 4 (PF4) were observed as soon as 24 hr after beginning of the therapy. This “rebound effect” of PGI2 on platelets is of an unknown mechanism but exhaustion of the platelet adenylate-cyclase system is one of possible explanations.