DIPHENHYDRAMINE PROTECTION OF THE FAILING MYOCARDIUM DURING GRAM-NEGATIVE ENDOTOXEMIA

Abstract

Gram-negative endotoxin (Escherichia coli, 4 mg/kg) in dogs produced a sustained fall in systemic arterial pressure, left ventricular pressure and cardiac output that was blocked by the histamine antagonist, diphenhydramine. Histamine infusion produced a parallel depression of systemic arterial pressure. Endotoxemia produced a significant depression of myocardial contractility (dP/dtmax) [maximum pressure change with time] that was blocked by diphenhydramine. Cardiac myofibrillar ATPase activity from endotoxin-shocked hearts was depressed. ATPase activity from subendocardial myofibrils was more depressed than that of subepicardial myofibrils. Myofibrillar ATPase activity was significantly protected by pretreating the animals with diphenhydramine. The initial hemodynamic phase of endotoxin shock is histamine-mediated and this hemodynamic depression can be blocked with diphenhydramine. Endotoxin is apparently capable of depressing myocardial contractility by depressing contractile protein function (myofibrillar ATPase activity), the subendocardial surface more so than the subepicardial surface, and this depression of myocardial contractility can be blocked with diphenhydramine.