Prostaglandin redirection by thromboxane synthetase inhibition. Attenuation of myocardial stunning in canine heart

We have previously reported that inhibition of thromboxane synthesis results in an improvement in postischemic function in stunned myocardium of dogs. The purpose of the present study was to investigate further the mechanism by which thromboxane synthesis inhibition improves recovery of function in stunned myocardium (15 minutes of coronary occlusion and 3 hours of reperfusion) in barbital anesthetized dogs. The recovery of regional myocardial wall function (percent segment shortening, % SS) following treatment with two doses (0.5 and 10 mg/kg) of a thromboxane receptor blocker, BM 13.505, given prior to coronary occlusion, was not different from that of a control group (3-hour % SS of pretreatment control, PTC, 12 +/- 11) throughout reperfusion (3-hour % SS of PTC with BM 13.505: 0.5 mg/kg 14 +/- 10; 10 mg/kg, 27 +/- 9). In contrast, the specific thromboxane synthetase inhibitor, dazmegrel (3.0 mg/kg), significantly improved % SS throughout reperfusion (3-hour % SS of PTC, 66 +/- 8). In addition, while dazmegrel produced a marked decrease in thromboxane, 6-keto-PGF1 alpha was significantly increased in coronary venous blood throughout the occlusion and reperfusion period. The cyclooxygenase inhibitor, indomethacin, had no bene...Continue Reading