Salutary actions of thromboxane synthetase inhibition during global myocardial ischemia.
Isolated cat hearts were perfused with blood-free Krebs-Henseleit solution for 165 min. Ischemia was induced by reducing perfusion to 0.02 ml/min/g wet heart weight for 2 h followed by reperfusion at controls flows for 30 min. Hearts perfused with the thromboxane synthetase inhibitor OKY-1581 at concentrations of 5 X 10(-6) M were spared from the increases in circulating thromboxane B2 occurring in untreated ischemic hearts. After reperfusion, cardiac contractile force increased to a higher level in OKY-1581 treated hearts. This was associated with a lower coronary vascular resistance than in untreated ischemic hearts. OKY-1581 treated ischemic hearts exhibited lower perfusate and higher myocardial creatine kinase (CK) activity than untreated ischemic hearts, indicative of preservation of cellular integrity. Also, OKY-1581 treated ischemic hearts showed improved lysosomal stability as evidenced by a lower tissue percent free cathepsin D activity than untreated ischemic hearts. These results are consistent with a significant role of thromboxanes in the propagation of myocardial cellular damage during ischemia.
D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D002402:Cathepsin D; D002403:Cathepsins / Q000378:metabolism; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008247:Lysosomes / Q000187:drug effects; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors
D000179:Acrylates; D008689:Methacrylates; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D010088:Oxidoreductases; D003402:Creatine Kinase; D002403:Cathepsins; D002402:Cathepsin D; D013930:Thromboxane-A Synthase