Interaction of platelets with the vessel wall in the pathophysiology of sudden cardiac death.

The occurrence of ventricular fibrillation after occlusion of the circumflex coronary artery in the conscious dog was examined as one preparation for sudden cardiac death arising from coronary artery disease. The incidence of ventricular fibrillation after after circumflex occlusion was reduced from 53% to 6% (p less than .01) by the infusion of prostacyclin in doses that do not alter cardiac output or peripheral resistance. This effect of prostacyclin led to the evaluation of two structurally different inhibitors of thromboxane synthase in this preparation; RO 22-4679 and U-63557A reduced ventricular fibrillation by 82% and 100%, respectively (p less than .05). The inhibition of ventricular fibrillation by U-63557A was abrogated by pretreatment with indomethacin, suggesting that a metabolite of the endoperoxide that accumulated during thromboxane synthase inhibition was responsible for the protection from ventricular fibrillation.