PLATELET-MEDIATED ALTERATIONS IN CARDIAC CELLULAR ELECTROPHYSIOLOGY

Recent clinical and experimental evidence indicates that platelet activation contributes to the arrhythmogenic effects of myocardial ischaemia, but little is known about the electrophysiological effects produced by controlled platelet activation under conditions of normal perfusion and how these might relate to effects during ischaemia. To investigate this, we studied changes in cardiac cellular electrophysiology and arrhythmogenesis during infusion of platelets [10(8)/ml] in isolated, perfused guinea-pig hearts during normal perfusion and global myocardial ischaemia. Hearts were studied in four groups: group A (n = 4) receiving frozen/thawed (activated) platelets; group B (n = 4) receiving normal platelets in the presence of 10(-9) M platelet activating factor (PAF); group C (n = 9) receiving buffer only during normal perfusion and myocardial ischaemia; group D (n = 9) receiving platelets during normal perfusion and myocardial ischaemia. Infusion of platelets (group D) had no effects during normal perfusion, but activated platelets (group A) decreased action potential duration (APD) from 165 +/- 1 ms to 138 +/- 5 ms (mean +/- SE) at 15 min of normal perfusion (P < 0.02) and produced ventricular fibrillation (VF) in 3/4 at 21 +/- 1 min. Infusion of platelets in the presence of PAF (group B) produced similar reductions of APD during normal perfusion and VF in 2/4. During ischaemia, platelets (group D) increased the incidence of VF (100% vs 56% group C, P < 0.05) and enhanced the ischaemia-induced reductions in APD (107 +/- 3 ms vs 121 +/- 5 ms (group C) P < 0.05 at 15 min). These studies demonstrate that (i) infusion of activated platelets produces deleterious electrophysiological and arrhythmogenic effects in normally-perfused hearts; (ii) myocardial ischaemia causes platelet activation which contributes to the electrophysiological and arrhythmogenic effects observed.