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Eur J Cardiothorac Surg 2006;30:472-479
© 2006 Elsevier Science NL

Effects of nicorandil preconditioning on membrane dystrophin

^a Department of Surgery, Kurume University, 67 Asahi-machi, Kurume 830-0011, Japan
^b Department of Pharmacology, Kurume University, 67 Asahi-machi, Kurume 830-0011, Japan

Received 17 November 2005; received in revised form 20 April 2006; accepted 1 June 2006.

^_* Corresponding author. Tel.: +81 942 35 3311; fax: +81 942 35 8967. (Email: shojima{at}med.kurume-u.ac.jp).

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 K_ATP 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 60 min of cardioplegic arrest, followed by 60 min 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 30 min before heart isolation. The nicorandil group received nicorandil (0.3 mg/kg) intravenously 30 min before isolation. The 5-HD group received 5-hydroxydecanoate (1 mg/kg) intravenously, a mitochondrial K_ATP channel blocker, 5 min 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 60 min 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.

Key Words: Myocardial preconditioning • Mitochondrial K-ATP channel • Ischemia–reperfusion injury • Cardioplegia