Effect of Thromboxane A2 Synthetase Inhibitor on Metabolism and Contractility in Ischemic Reperfused Rabbit Heart

Abstract

The effect of thromboxane A2 synthetase inhibitor (OKY-046) on myocardial metabolism and contractility during ischemia and reperfusion was examined by the phosphorus 31- nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts with use of an arti ficial blood substitute, perfluorochemical emulsion Fluosol-43. After normothermic fifteen-minute global zero-flow ischemia or fifteen-minute global low-flow ischemia (coronary perfusion pressure = 20 mmHg), reperfusion of sixty minutes was carried out. OKY-046 was administered from forty-five minutes prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (CrP), inorganic phosphate (Pi), pH, left ventricular systolic developed pressure (LV Dev.P) and coronary flow were continu ously measured. Twenty-eight hearts were divided into four experimental groups consisting of 7 hearts each; Group I consisted of controls with zero-flow ischemia; Group II, perfusion with OKY-046 (10-6 M) in zero-flow ischemia; Group III, controls with low- flow ischemia; and Group IV, perfusion with OKY-046 in low-flow ischemia. Group II showed a significant inhibition of the increase in Pi and of the decrease in ATP, CrP, and pH during global ischemia compared with Group I, and a suppression of the overshoot of CrP observed after postischemic reperfusion. Group IV also showed a significantly marked improvement of ATP, CrP, and pH and significant suppression in Pi during low-flow ischemia compared with Group III. There were no differences in LV Dev.P and coronary flow among any groups. In conclusion, OKY-046 has a significantly beneficial effect on metabolism during both myocardial ischemia and reperfusion.