Isoflurane Produces Delayed Preconditioning against Myocardial Ischemia and Reperfusion Injury: Role of Cyclooxygenase-2

Abstract

Background: Whether volatile anesthetics produce a second window of preconditioning is unclear. The authors tested the hypothesis that isoflurane causes delayed preconditioning against infarction and, further, that cyclooxygenase (COX)-2 mediates this beneficial effect. Methods: Rabbits (n = 43) were randomly assigned to receive 0.9% intravenous saline, the selective COX-2 inhibitor celecoxib (3 mg/kg intraperitoneal) five times over 2 days before coronary artery occlusion and reperfusion, or isoflurane (1.0 minimum alveolar concentration) 24 h before acute experimentation in the absence or presence of celecoxib pretreatment. Two additional groups of rabbits received a single dose of celecoxib either 30 min before or 21.5 h after administration of isoflurane. Rabbits were then instrumented for measurement of hemodynamics and underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Myocardial infarct size was measured using triphenyltetrazolium staining. Western immunoblotting to examine COX-1 and COX-2 protein expression was performed in rabbit hearts that had or had not been exposed to isoflurane. Results: Isoflurane significantly (P < 0.05) reduced infarct size (22 ± 3% of the left ventricular area at risk) as compared with control (39 ± 2%). Celecoxib alone had no effect on infarct size (36 ± 40%) but abolished isoflurane-induced cardioprotection (36 ± 4%). A single dose of celecoxib administered 2.5 h before coronary occlusion and reperfusion also abolished the delayed protective effects of isoflurane (36 ± 4%), but celecoxib given 30 min before exposure to isoflurane had no effect (22 ± 4%). Isoflurane did not alter COX-1 and COX-2 protein expression. Conclusions: The results indicate that the volatile anesthetic isoflurane produces a second window of preconditioning against myocardial ischemia and reperfusion injury. Furthermore, COX-2 is an important mediator of isoflurane-induced delayed preconditioning.