Protection of Ischemic Cat Myocardium By CGS13080 a Selective Potent Thromboxane A2Synthesis Inhibitor

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 its effects on isolated cat coronary arteries, in vitroaggregation 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, TxB2concentrations, plasma and tissue CK activities, and myocardial amino-nitrogen concentration in 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 TxA2analog and did not inhibit aggregation of cat PRP induced by arachidonic acid (AA). However, production of TxB2by cat platelets treated with AA was completely inhibited by this agent. Thus, specific inhibition of TxA2synthesis without thromboxane receptor antagonism can exert a protective effect on the myocardium during ischemia in cats.