PLATELET-ACTIVATING-FACTOR AND CARDIAC DISEASES - THERAPEUTIC POTENTIAL FOR PAF INHIBITORS

Platelet-activating factor (PAF) is a potent phospholipid mediator rel eased from inflammatory cells in response to diverse immunologic and n on-immunologic stimuli. Animal studies have implicated PAF as a major mediator involved in coronary artery constriction, modulation of myoca rdial contractility and the generation of arrhythmias which may bear o n cardiac disorders such as ischemia, infarction and sudden cardiac de ath. PAF effects are induced by direct actions of PAF on cardiac tissu e to modify chronotropic and inotropic activity, or indirectly via the release of eicosanoids such as thromboxane A(2) (TXA(2)), leukotriene s (LT) or cytokines (TNF alpha). The development of selective, high af finity PAF receptor antagonists has permitted investigations on the ro le of PAF in experimental animal models of cardiac injury. In vivo and in vitro studies strongly suggest that PAF receptor antagonists might convey therapeutic benefits in ischemic conditions and certain arrhyt hmias. In addition, PAF antagonists might have a cardiac allograft-pre servation effect. Although clinical studies with PAF receptor antagoni sts in patients with cardiac diseases have not yet been reported, the experimental results to date suggest that PAF receptor antagonists mig ht be useful in some specific cardiac disorders in humans. Copyright ( C) 1997 Elsevier Science B. V.