title: Influence of intracoronary platelet aggregation on ventricular electrical properties during partial coronary artery stenosis.
abstract: Several clinical studies suggest that drugs which interfere with platelet function may protect persons at risk for sudden death. However, there is no direct evidence that intracoronary platelet aggregation produces cardiac arrhythmias. Induction of fixed partial coronary stenoses in dogs resulted in spontaneous cyclical reductions in coronary blood flow of 21 to 81% (p less than 0.01). These changes are known to be associated with the formation and distal embolization of platelet aggregates. These reductions in coronary blood flow were accompanied by significant decreases in the repetitive extrasystole (-40%) and ventricular fibrillation (-38%) thresholds. Prostacyclin (PGI2), a potent vasodilator and inhibitor of platelet activation, in increasing doses of from 25 to 100 ng/kg/min caused a stepwise decrease in the frequency and magnitude of coronary blood flow fluctuations and restored the vulnerable period thresholds to control levels. Indomethacin (5 mg/kg), an inhibitor of cyclo-oxygenase activation and platelet thromboxane A2 production, produced similar results. The mechanism of coronary blood flow reduction appears to be mechanical blockade of the vessel lumen by platelet thrombi and production of myocardial ischemia. These results suggest that intracoronary platelet aggregation contributes to electrical destabilization of the myocardium and may predispose to ventricular fibrillation. A model is thus available for further investigating the role of platelets and antiplatelet drugs in modulating ventricular electrical stability.
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D005117:Cardiac Complexes, Premature / Q000188:drug therapy / Q000503:physiopathology; D003326:Coronary Circulation; D003327:Coronary Disease / Q000209:etiology / Q000503:physiopathology*; D004285:Dogs; D004594:Electrophysiology; D011464:Epoprostenol / Q000008:administration & dosage; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D011464:Epoprostenol; D007213:Indomethacin