U-63,557A, a new selective
thromboxane synthetase inhibitor, was evaluated for its ability to prevent the extension of
myocardial infarct size. Left coronary arteries of male Sprague-Dawley rats (230 - 270 g) were acutely ligated, producing a consistent model of
myocardial infarction (MI) in rats analyzed 48 hours later. Left ventricular free wall (LVFW),
creatine kinase (CK) activity, and amino-
nitrogen concentrations were assayed as indices of
infarct size. U-63,557A was administered intravenously in two doses (4 and 8 mg/kg) with a split schedule (2 min post-
ischemia and either 4 or 24 hrs later). Administration of the
thromboxane synthetase inhibitor significantly reduced both myocardial CK and amino-
nitrogen loss at a dose of 8 mg/kg, but it was only slightly effective at 4 mg/kg.
Drug treatment significantly increased the percent LVFW spared; 27 +/- 3% (vehicle) vs 43 +/- 7% and 52 +/- 7% (8 mg/kg). U-63,557A is an effective agent in
myocardial ischemia for limiting the extension of
infarct size after acute coronary artery
ligation. Previous studies of other
thromboxane synthetase inhibitors showed effectiveness in the early stages of MI. This study shows an effect on true
infarct size 48 hours post-
ligation, and suggests that inhibition of
thromboxane A2 plays an important role in the pathogenesis of ischemic damage in the myocardium.