Parecoxib Inhibits Apoptosis in Acute Myocardial Infarction Due to Permanent Coronary Ligation But Not Due to Ischemia-Reperfusion

Abstract

PURPOSE: Myocardial ischemia induces cyclooxygenase 2 (COX-2) expression. We evaluated the effects of parecoxib, a COX-2 inhibitor, in 2 different mouse models of myocardial ischemia: permanent left coronary artery ligation (PI) and transient ligation (30 minutes ischemia) followed by reperfusion (I/R). METHODS: Forty adult male Institute of Cancer Research mice underwent PI (n = 24) or I/R (n = 16), followed by randomization to parecoxib (0.75 mg/kg intraperitoneal daily) or normal saline for 7 days. RESULTS: Parecoxib significantly reduced apoptosis [0.8% vs. 3.4% (saline), P < 0.001] and 7-day mortality [0% vs. 57% (saline), P = 0.040] in the PI group but showed no benefit in the I/R group. Parecoxib-treated mice also exhibited greater fractional shortening in the PI group [22% vs. 14% (saline), P = 0.045) but not in the I/R group. Parecoxib did not affect infarct size in either group. CONCLUSIONS: COX-2 may play a pivotal role in mediating apoptosis in the ischemic peri-infarct myocardium that is not reperfused after infarct.