Preservation of ischemic myocardium by pinane thromboxane A2

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Abstract
Pinane thromboxane A2 (PTA2), a thromboxane [TB] A2 analog, antagonizes the vasoconstriction and platelet aggregation induced by TB A2, in addition to specifically inhibiting TB synthetase. Because TB A2 generation would be detrimental in acute myocardial ischemia (MI) by both decreasing coronary blood flow and increasing platelet aggregation, inhibition of TB production and action may be beneficial in MI. In pentobarbital-anesthetized cats, the left anterior descending coronary artery was ligated and PTA2 (0.5 .mu.ol/kg per h) or a Na2CO3 vehicle was infused 30 min post-MI for 270 min. Compared to vehicle treated MI cats, PTA2 prevented the increase in plasma TB levels seen at 2 through 5 h (P < 0.005 at 2 through 5 h) and prevented the large increase in plasma CK [creatinine kinase] activities at 4 and 5 h (P < 0.025). PTA2 treatment abolished the differences in myocardial CK activities between ischemic and nonischemic regions and prevented the decrease in percent-bound cathepsin D in the ischemic region. ECG analysis revealed a decreased incidence of premature beats in PTA2-treated MI cats as compared to MI-vehicle cats. These data indicate that PTA2 protects the ischemic myocardium and inhibition of thromboxane formation, in addition to antagonism of its activity, is beneficial during the early stages of acute myocardial ischemia.