MYOCARDIAL-ISCHEMIA INDUCES PLATELET ACTIVATION WITH ADVERSE ELECTROPHYSIOLOGICAL AND ARRHYTHMOGENIC EFFECTS

Objective: The aim was to investigate how platelet activation during m yocardial ischaemia can induce electrophysiological and arrhythmogenic effects, and examine the involvement of different platelet membrane r eceptors in producing these effects. Methods: Transmembrane action pot entials and electrograms were recorded from isolated, Langendorff perf used guinea pig hearts during normal perfusion, global myocardial isch aemia, and reperfusion during infusion of human platelets. Platelet re activity was altered by treating platelets with forskolin, aspirin, th e platelet activating factor (PAF) receptor antagonist BN 52021, the t hromboxane A(2) (TP) receptor antagonist GR 32191B, and the alpha(2) a drenoceptor antagonist yohimbine. Myocardial catecholamine depletion w as induced by treatment with 6-hydroxydopamine. Results: Platelet infu sion had no electrophysiological effects during normal perfusion, but during ischaemia it enhanced the reduction in action potential duratio n at 95% repolarisation [APD(95), 110(SEM 3) ms v 121(5) ms, p<0.05, a t 15 min] and increased the incidence of ventricular arrhythmias (from 56% to 94%, p = 0.04) compared to hearts receiving buffer but no plat elets. The reductions in APD,, and the arrhythmogenic effects were att enuated when forskolin treated, aspirin treated or GR 32191B treated p latelets were infused (VF: 50% v 94%, p = 0.03; 50% v 94%, p = 0.02; 2 2% v 94%, p<0.001, respectively). Similar results were obtained when n ormal platelets were infused into catecholamine depleted hearts (VF: 6 0% v 94%, p = 0.0549). These differences were associated with inhibite d aggregatory responses to thrombin (for forskolin treated platelets) and the thromboxane mimetic U44069 (far GR 32191B treated platelets). Yohimbine was antiarrhythmic in the presence and absence of platelets, suggesting direct myocardial effects, but BN 52021 had no antiarrhyth mic effects. Conclusions: Myocardial ischaemia causes platelet activat ion resulting in electrophysiological and arrhythmogenic effects. PAF receptor antagonism does not prevent these effects, but inhibition of platelet reactivity, platelet thromboxane receptor antagonism, and myo cardial catecholamine depletion are effective. These findings suggest that the arrhythmogenic effects of platelet activation during myocardi al ischaemia are principally mediated by a thromboxane dependent mecha nism, while catecholamine release has a contributory role.