Inhibition of c‐Jun N‐terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats

Myocardial ischemia/reperfusion is associated with inflammation, apoptosis and necrosis. During this process, c‐jun N‐terminal kinase is activated in cardiac myocytes resulting in apoptosis. This study investigates the effects of AS601245, a nonpeptide ATP competitive JNK inhibitor, on infarct size caused by myocardial ischemia/reperfusion in anaesthetized rats. The left descending coronary artery of anaesthetized rats was occluded for 30 min and then reperfused for 3 h. AS601245 was administered 5 min before the end of the ischemia period as an i.v. bolus (1.5, 4.5 or 15 mg kg−1 i.v.) followed by continuous i.v. infusion (18, 55 and 183 μg kg−1 min−1, respectively) during reperfusion. Controls received saline only. 3‐Aminobenzamide, a poly(ADP‐ribose) polymerase inhibitor, was used as reference compound at 10 mg kg−1 i.v. bolus plus 0.17 mg kg−1 min−1 continuous infusion. AS601245 significantly reduced infarct size at 4.5 mg kg−1 (−44%; P