Platelet-Activating-Factor-Induced Changes in Cardiovascular Function and Oxyradical Status of Myocardium in Presence of the PAF Antagonist CV-6209

Abstract

The effects of platelet-activating factor (PAF) on cardiac function and con tractility and its mechanism of action are not fully understood. The authors investigated the effects of PAF in the absence or presence of a potent PAF antag onist CV-6209 on the cardiac function and contractility; lipid peroxidation prod uct malondialdehyde (MDA), an indirect measure of oxygen free radicals; serum creatine kinase (CK); blood lactate; and pH in anesthetized dogs. CV- 6209 (1 mg/kg, IV) did not produce significant changes in the various parame ters studied. PAF (1 μg/kg, IV) produced decreases in the cardiac function (cardiac index, left ventricular work index) and indices of cardiac contractility [(+) and (-) dp/dt, dp/dt at CPIP, (dp/dt)/IP, dp/dt at CPIP/IP, V_max] and in creases in the systemic and pulmonary vascular resistance. It also produced increases in cardiac MDA, serum CK, blood lactate, and H⁺ and decreases in blood pH and HCO₃ ^- . CV-6209 completely prevented the PAF-induced changes in the hemodynamic and biochemical parameters.

These results suggest that PAF-induced cardiac depression may be due to PAF-induced release of oxyradicals from neutrophils and that PAF antagonist may be useful in counteracting the deleterious effects of PAF on the cardiovas cular system.