Resistance of Platelets to Prostacyclin

Abstract

Prostacyclin (PGI₂) is an important homeostatic compound involved in the interaction of platelets with endothelial cells. Its outstanding properties are a platelet antiaggregatory effect, vasodilation, and “cytoprotection”. The activity profile of this compound looks promising for the treatment of ischemic and necrotic syndromes. When applied in patients suffering from these, its effectiveness (relation dose/result) can be surprisingly low. To improve therapeutical efficacy, higher doses appear to be necessary, but the number of side effects will also increase. On the other hand, in atherosclerotic patients or in animals on an atherosclerotic diet or with thrombosis, increased concentrations of prostacyclin in the blood have been reported. These two factors led us to the study of the responsiveness of platelets to prostacyclin under conditions such as acute heart attack or advanced atherosclerotic disease. Platelet resistance to prostacyclin is defined as a metabolic or pathophysiological condition in which platelets exhibit a reduction in response to the antiaggregatory and/or antisecretory effect of prostacyclin or prostacyclin analogues. In this presentation we would like to restrict ourselves to in vitro and ex vivo results.