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.