Activation of protein kinase C contributes to the isoflurane-induced improvement of functional and metabolic recovery in isolated ischemic rat hearts.
Isoflurane enhances myocardial functional recovery and improves energy levels after ischemia. We sought to determine whether isoflurane-induced cardioprotection is mediated by protein kinase C (PKC). The Langendorff model was used, and isolated perfused rat hearts were separated into untreated, isoflurane, chelerythrine (PKC inhibitor) plus isoflurane, and chelerythrine groups. All hearts were subjected to treatment before ischemia, followed by 30 min of ischemia and 60 min of reperfusion. We recorded hemodynamic variables, measured metabolites by high-performance liquid chromatography, and analyzed subcellular localization of PKC isoforms by Western blot analysis. Isoflurane significantly improved the recovery of left ventricular developed pressure, attenuated the depletion of myocardial adenosine triphosphate (ATP) and creatine phosphate at 15 min of ischemia, enhanced the recovery of myocardial ATP and creatine phosphate concentrations after ischemia, and was associated with the translocation of PKC-delta and -epsilon to the membrane. Chelerythrine suppressed the translocation of PKC-delta and -epsilon and blocked the improvement of cardiac function and ATP. We conclude that isoflurane delays the decrease in ATP during ischemia and improves the recovery of mechanical function and the energy state 60 min after ischemia. These effects of isoflurane are dependent on the activation of PKC.
Xu
Pengcheng
P
Departments of *Anesthesiology and ‡Physiology & Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York; and †Anesthesiology Key Laboratory of Jiangsu Province, Xuzhou Medical College, Xuzhou, People's Republic of China.
Wang
Jun
J
Kodavatiganti
Ramesh
R
Zeng
Yinming
Y
Kass
Ira S
IS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000470:Alkaloids; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D053119:Benzophenanthridines; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000470:Alkaloids; D018685:Anesthetics, Inhalation; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010617:Phenanthridines; D011506:Proteins; D000255:Adenosine Triphosphate; D007530:Isoflurane; C016299:chelerythrine; D011493:Protein Kinase C