Preservation of myocardium in transient ischemia by the thromboxane synthetase inhibitor UK 38.485.
This study was performed to examine potential protective effects of UK 38.485, an inhibitor of thromboxane synthetase, in canine myocardium stressed by transient ischemia. On anesthetized open-chest mongrel-dogs (n = 9) repeated ischemia (3 min) was produced by proximal, intermittent occlusion of the left anterior descending artery. A total of 18 occlusions after 3 mg UK 38.485/kg body wt. and 12 occlusions after 5 mg UK 38.485/kg body wt. were compared to a total of 24 occlusions under control conditions. In each experiment, 2-3 control occlusions and 3-4 therapy occlusions were performed. The drug was applied i.v. in a dose of 3 or 5 mg/body wt. 30 min before the first therapy occlusion. In both groups, hemodynamics and energetics did not significantly change as compared to control. The efficiency of the drug in protecting ischemically stressed myocardium was examined by (a) quantification of oxygen debt and oxygen repayment in the occlusion and reperfusion periods and (b) the amounts of inorganic phosphate, lactate, and potassium released in the first minute of reperfusion. Compared to control occlusions, premedication with either 3 or 5 mg UK 38.485 led to a significantly reduced oxygen debt combined with a significant decrease of the release of inorganic phosphate, lactate, and potassium. The protective effect is suggested to be mainly due to enhanced flow to ischemic areas. Data obtained in this study suggest protective effects of the compound in the preservation of myocardium in transient ischemia and attest to the concept that thromboxane A2 may aggravate the metabolic and energetic situation of myocardium in circumstances with reduced oxygen supply.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D007093:Imidazoles; C039242:dazmegrel; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase