Protection of ischemic cat myocardium by CGS-13080, a selective potent thromboxane A2 synthesis inhibitor.

Abstract

A specific inhibitor of thromboxane A2 (TxA2) synthesis, CGS-13080, was studied during acute myocardial ischemia (MI) in cats. To define more clearly the mechanism of action of CGS-13080, we also studied it effects on isolated cat coronary arteries, in vitro aggregation of cat platelets, and production of thromboxane B2 (TxB2) from cat platelet-rich plasma (PRP). MI cats that received the vehicle for CGS-13080 exhibited a significant increase in plasma concentration of TxB2. This was accompanied by increases in the ST segment of the electrocardiogram, specific activity of plasma creatine kinase (CK), and loss of CK activity and amino-nitrogen from the ischemic myocardium. In contrast, TxB2 concentrations, plasma and tissue CK activities, and myocardial amino-nitrogen concentration of MI cats treated with CGS-13080 were not significantly different from those in sham MI cats that had received the drug. In vitro, CGS-13080 did not inhibit contraction of cat coronary arteries produced by a stable TxA2 analog and did not inhibit aggregation of cat PRP indiced by arachidonic acid (AA). However, production of TxB2 by cat platelets treated with AA was completely inhibited by this agent. Thus, specific inhibition of TxA2 synthesis without thromboxane receptor antagonism can exert a protective effect on the myocardium during ischemia in cats.