Roles of cyclooxygenase 2 in sevoflurane- and olprinone-induced early phase of preconditioning and postconditioning against myocardial infarction in rat hearts.

摘要

PURPOSE: It is known that selective cyclooxygenase 2(COX-2) inhibitors increase mortality in patients with previous myocardial infarction, and it has been suggested that COX-2 plays an important role in cardioprotection against ischemia. The current study was carried out to determine whether COX-2 is involved in the mechanisms of sevoflurane- and olprinone-induced early-phase preconditioning (E-PreC) and postconditioning (PostC) in rat hearts. METHODS: Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-minute occlusion of left anterior descending coronary artery followed by 2-hour reperfusion, and the infarct size was measured after the reperfusion. The rats were randomly assigned to groups with pre- and postischemic exposure to sevoflurane and administration of olprinone with or without a selective COX-2 inhibitor, NS-398. RESULTS: The infarct size in the control group was 42% +/- 6% of the area at risk. Infarct size was significantly reduced by pre- and postischemic administration of sevoflurane (16% +/- 7% and 17% +/- 6%, respectively), as well as by olprinone (14% +/- 4% and 15% +/- 10%, respectively). NS-398 prevented the protective effects of both pre- and postischemic exposure to sevoflurane (35% +/- 8% and 42% +/- 10%, respectively), whereas the protective effect of both pre- and postischemic administration of olprinone was not influenced by NS-398 (12% +/- 5% and 19% +/- 7%, respectively). CONCLUSIONS: Cyclooxygenase 2 could be a critical mediator of sevoflurane-induced but not olprinone-induced E-PreC or PostC in rat hearts.