Intestinal ischemia preconditions myocardium: role of protein kinase C and mitochondrial K(ATP) channel.
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 K(ATP) 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 microg/kg) or a specific mitochondrial K(ATP) 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 K(ATP) channel are involved in the mechanism of the early preconditioning induced by intestinal ischemia.
Wang
You-Ping
YP
First Department of Surgery, Kagawa Medical University, 1750-1, Ikenobe, Miki, Kita, Japan. wang@kms.ac.jp
Maeta
Hajime
H
Mizoguchi
Kazuhiro
K
Suzuki
Takeo
T
Yamashita
Yoichi
Y
Oe
Masahiro
M
D000470:Alkaloids; D000704:Analysis of Variance; D000818:Animals; D053119:Benzophenanthridines; D001794:Blood Pressure; D003652:Decanoic Acids / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D007422:Intestines / Q000098:blood supply*; D019194:Ischemic Preconditioning / Q000379:methods*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000378:metabolism; D010617:Phenanthridines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors
D000470:Alkaloids; D053119:Benzophenanthridines; D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D006880:Hydroxy Acids; D010617:Phenanthridines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; C016299:chelerythrine; D011493:Protein Kinase C; D019311:Staurosporine