CGS-12970, a thromboxane synthetase inhibitor, limits ischemic damage following coronary artery occlusion

A new thromboxane synthetase inhibitor, CGS-12970, was evaluated for its ability to reduce the extension of myocardial infarct size in rats. CGS-12970 was given at either 4 or 8 mg/kg following acute coronary artery ligation. Both myocardial creatine kinase (CK) and amino-nitrogen loss from the left ventricular free wall (LVFW) were used as indices of ischemic damage at 48 hours. Rats given only the vehicle following coronary artery ligation lost 4.9 +/- 0.5 IU/mg protein (p less than 0.001) CK activity from the LVFW. This loss of CK activity was only slightly reduced by CGS-12970 at 4 mg/kg. However, at 8 mg/kg, the CK depletion from the LVFW was significantly reduced (p less than 0.05). This protective effect was confirmed by similar curtailment (p less than 0.05) of the loss of nitrogenous compounds from ischemic myocardium, at the high dose of CGS-12970. These findings represent a protective effect of CGS-12970 in reducing the extent of ischemic cardiac damage following experimental coronary artery ligation.