The Cardioprotective Effect of Intravenous Nicorandil for Ischemia/Reperfusion Injury

ABSTRACT

BACKGROUND AND OBJECTIVES: Nicorandil is a potassium channel opener, and it has been known to have a cardioprotective effect against ischemia/reperfusion injury. However, the exact mechanisms of the effect are not known. In the previous studies on cardioprotection, administration of nicorandil was started early during the coronary occlusion. Therefore, it is not clear whether nicorandil can also be beneficial when it is administered from the time of coronary recannalization. MATERIALS AND METHODS: We studied 15 cats that had their chests surgically opened (8 nicorandil cats and 7 control cats). The proximal portion of the left anterior descending artery (LAD) was occluded with ligation for 90 minutes, then it was recannalized for 60 minutes. Intravenous injection of nicorandil was started at the time of recannalization of the artery (a bolus of 100 microgram.kg(-1) plus an infusion at a rate of 10 microgram.kg(-1).min(-1) ). At each stage of the experiments, the risk area and myocardial perfusion were assessed using color microspheres and myocardial contrast echocardiography. The size of the infarction was evaluated by postmortem triphenyltetrazolium chloride staining. Myocardial contrast echocardiography was performed with Pulse Inversion Harmonic Imaging (Sonoace9900, Medison). RESULTS: The risk area during coronary occlusion was 18.8+/-12.6% in the nicorandil group and 19.3+/-9.6% in the control group (p=NS). The perfusion defect immediately after and 1 hour after reperfusion was 13.0+/-8.7% and 8.4 +/-7.6%, respectively, in nicorandil group, and 16.7 +/-11.1 % and 13.4+/-8.8%, respectively, in the control group, (p=NS between groups). Myocardial blood flow in the LAD territory during occlusion immediately after and 1 hour after reperfusion was 56+/-31 %, 73+/-31 % and 69+/-28%, respectively, of the normal myocardium in the nicorandil group, and 65+/-20%, 101+/-75% and 77+/-42%, respectively, in the control group (p=NS between groups). The postmortem infarction size was 8.1+/-9.6% in the nicorandil group and 7.7+/-7.5% in the control group (p=NS). CONCLUSION: With administration of nicorandil from the time of recannalization in the ischemia/reperfusion injury model, we could not find any significant cardioprotective effect. The cardioprotective effect of nicorandil may be associated with preconditioning before reperfusion.