Effects of nicorandil preconditioning on membrane dystrophin.
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.
Shojima
Takahiro
T
Department of Surgery, Kurume University, 67 Asahi-machi, Kurume 830-0011, Japan. shojima@med.kurume-u.ac.jp
Hayashida
Nobuhiko
N
Nishi
Akinori
A
Takagi
Kazuyoshi
K
Hori
Hidetugu
H
Yoshikawa
Kazuhiro
K
Aoyagi
Shigeaki
S
D000818:Animals; D003326:Coronary Circulation / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D016189:Dystrophin / Q000032:analysis*; D005455:Fluorescent Antibody Technique / Q000379:methods; D006321:Heart / Q000503:physiopathology; D006324:Heart Arrest, Induced / Q000379:methods; D015151:Immunoblotting / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D018613:Microscopy, Confocal / Q000379:methods; D008929:Mitochondria, Heart / Q000378:metabolism; D017202:Myocardial Ischemia / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D020108:Nicorandil / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D012508:Sarcolemma / Q000737:chemistry; D014665:Vasodilator Agents / Q000494:pharmacology*; D016596:Vinculin / Q000032:analysis
D016189:Dystrophin; D015221:Potassium Channels; D014665:Vasodilator Agents; D016596:Vinculin; D020108:Nicorandil; D003402:Creatine Kinase