Effects of nicorandil preconditioning on membrane dystrophin

Shojima, Takahiro; Hayashida, Nobuhiko; Nishi, Akinori; Takagi, Kazuyoshi; Hori, Hidetugu; Yoshikawa, Kazuhiro; Aoyagi, Shigeaki
September 2006
European Journal of Cardio-Thoracic Surgery;Sep2006, Vol. 30 Issue 3, p472
Academic Journal
Abstract: Objective: Dystrophin is an integral membrane protein that stabilizes the sarcolemmal membrane integrity, and its loss may be involved in the mechanism of ischemia and reperfusion injury. It has been reported that ischemic preconditioning is related to the preservation of membrane dystrophin during ischemia and reperfusion. Preconditioning with nicorandil, a mitochondrial KATP channel opener, may attenuate the injury by preventing a disturbance in the level of this membrane-associated protein. Methods: The isolated rat hearts were subjected to 60min of cardioplegic arrest, followed by 60min of reperfusion. The hearts were divided into the following three groups according to the drugs given before cardioplegic arrest. The control group received saline intravenously 30min before heart isolation. The nicorandil group received nicorandil (0.3mg/kg) intravenously 30min before isolation. The 5-HD group received 5-hydroxydecanoate (1mg/kg) intravenously, a mitochondrial KATP channel blocker, 5min before nicorandil administration. Cardiac function, myocardial metabolism, dystrophin distribution and protein levels of dystrophin were assessed before and after cardioplegic arrest. Results: The nicorandil group showed significantly better cardiac function and a significant reduction in creatine kinase release during reperfusion. After 60min of cardioplegic arrest, dystrophin, which was distributed predominantly in the sarcolemmal membrane before ischemia, was translocated to the costameric cytoskeleton in all groups. During reperfusion, the level of membrane dystrophin remained decreased in the majority of cardiomyocytes in the control and 5-HD groups, whereas it was restored to nearly the baseline level in the nicorandil group. The immunoblot analysis supported this result. Conclusions: Depletion of sarcolemmal membrane dystrophin occurred during cardioplegic arrest and reperfusion. Nicorandil preconditioning may attenuate ischemia and reperfusion injury by maintaining the membrane structural integrity.


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