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Cardiovascular Research 2002 55(3):576-582; doi:10.1016/S0008-6363(02)00245-6
© 2002 by European Society of Cardiology
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Copyright © 2002, European Society of Cardiology

Intestinal ischemia preconditions myocardium: role of protein kinase C and mitochondrial KATP channel

You-Ping Wang*, Hajime Maeta, Kazuhiro Mizoguchi, Takeo Suzuki, Yoichi Yamashita and Masahiro Oe

First Department of Surgery, Kagawa Medical University, 1750-1, Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan

wang{at}kms.ac.jp

* Corresponding author. Tel.: +81-878-91-2186; fax: +81-878-91-2187

Objective: The present study was designed to test the hypothesis that intestinal ischemia results in an early preconditioning against myocardial infarction and that the mechanism of the early preconditioning involves the activation of protein kinase C-mitochondrial KATP channel signaling pathway in anesthetized rats. Methods: Rats were either preconditioned with a 25-min occlusion of the superior mesenteric artery followed by 15 min of reperfusion or underwent a 40-min sham period. Subsequently, all rats were subjected to a sustained 30 min of coronary occlusion and 180 min of reperfusion. Infarct size was determined by triphenyltetrazolium chloride staining. Results: In sham-operated rats receiving no pharmacological intervention, the percentage of myocardial infarct within the area at risk and left ventricle was 73±4% and 31±2%, respectively, and these were significantly reduced to 44±4% and 23±1% (P<0.01) after intestinal ischemia preconditioning. Intravenous injection of protein kinase C inhibitors chelerythrine (5 mg/kg) and staurosporine (50 µg/kg) or a specific mitochondrial KATP channel inhibitor 5-hydroxydecanoate (5 mg/kg) 5 min before sustained myocardial ischemia abolished the preconditioning afforded by intestinal ischemia. However, hexamethonium, a ganglion blocker, did not attenuate the preconditioning. Conclusions: These data provide pharmacological evidence that protein kinase C and mitochondrial KATP channel are involved in the mechanism of the early preconditioning induced by intestinal ischemia.

KEYWORDS Infarction; Ischemia; K-ATP channel; Mitochondria; Preconditioning; Protein kinases; Reperfusion


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