NEGATIVE INOTROPIC EFFECT OF PLATELET-ACTIVATING FACTOR ON HUMAN MYOCARDIUM - A PHARMACOLOGICAL STUDY

Publisher Website
Google Scholar
Abstract
Because platelet-activating factor (PAF) has prominent depressant effects on cardiac contractility in various mammalian species, we assessed the negative inotropic effect of PAF on noncoronary perfused human right atrial pectinate muscles paced at constant rate. We found that PAF is a potent negative inotropic agent (EC50 .apprxeq. 160 pM), whose action is unmodified by atropine, indomethacin and the leukotriene receptor antagonist compound FPL 55712. The negative inotropic effect of PAF was, however, antagonized by drugs known to inhibit PAF-induced platelet aggregation: the order of relative potency was SRI 63-441 > CV-3988 > alprazolam .gtoreq. triazolam; i.e., the same order in which these compounds antagonize the effects of PAF on platelets. Thus, the potent negative inotropic effect of PAF on human myocardium is independent of coronary flow changes, involves neither cholinergic mechanisms nor arachidonate metabolites and is probably mediated by specific receptors.