Nicorandil induces late preconditioning against myocardial infarction in conscious rabbits

Tang, Xian-Liang, Yu-Ting Xuan, Yanqing Zhu, Gregg Shirk, and Roberto Bolli. Nicorandil induces late preconditioning against myocardial infarction in conscious rabbits. Am J Physiol Heart Circ Physiol 286: H1273-H1280, 2004. First published December 18, 2003; 10.1152/ajpheart.0l055.2003.--Nicorandil has been shown to induce an infarct-limiting effect similar to that induced by the early phase of ischemic preconditioning (PC). The goals of this study were to determine whether nicorandil induces a delayed cardioprotection that is analogous to the late phase of ischemic PC and, if so, whether nicorandil-induced late PC is associated with upregulation of cardioprotective proteins. Chronically instrumented, conscious rabbits received vehicle (intravenous normal saline; control group, n = 10), nicorandil (100 [micro]g/kg bolus + 30 [micro]g.[kg.sup.-1].[min.sup.-1] iv for 60 min; nicorandil group, n = 10), or ischemic PC (6 cycles of 4-min coronary occlusion/4-min reperfusion; PC group, n = 8). Twenty-four hours later, rabbits underwent a 30-min coronary occlusion, followed by 3 days of reperfusion. Myocardial infarct size was significantly reduced in rabbits pretreated with nicorandil (27.5 [+ or -] 5.3% of the risk region) or with ischemia (30.3 [+ or -] 4.2%) versus controls (59.1 [+ or -] 4.7%, P < 0.05 vs. both). Furthermore, the expression of cyclooxygenase-2 (COX-2) and Bcl-2 was significantly elevated (+38% and + 126%, respectively; P < 0.05) in myocardium of rabbits given nicorandil 24 h earlier versus controls. We conclude that nicorandil induces delayed cardioprotection against myocardial infarction similar to that afforded by the late phase of ischemic PC, possibly by upregulating COX-2 and Bcl-2. Bcl-2; cyclooxygenase-2; infarct size; ischemia-reperfusion