Effects of protein kinase C inhibitors in in situ and isolated ischemic rabbit myocardium

Journal of Molecular and Cellular Cardiology
R D LasleyR M Mentzer

Abstract

We tested the effects of the protein kinase C (PKC) inhibitors bisindolylmaleimide (1 microM) and chelerythrine (2 microM) on myocardial ischemia-reperfusion injury in in situ and isolated perfused rabbit hearts. In non-ischemic isolated hearts, bisindolylmaleimide (1 microM) and chelerythrine (2 microM) blocked sn-1,2-dioctanoylglycerol (DOG)-induced coronary vasoconstriction by approximately 80%. Intact hearts were subjected to 45 min coronary artery occlusion and 2 h reperfusion. Infarct size, determined by triphenyltetrazolium chloride (TTC)-staining and expressed as percentage of risk area, was reduced approximately 50% by both bisindolylmaleimide (0.05 mg/kg, i.v.) and chelerythrine (0.1 mg/kg, i.v.) compared to vehicle treated controls. In contrast, a higher dose of chelerythrine (3.8 mg/kg, i.v.) did not significantly reduce infarct size. Isolated hearts were subjected to 45 min of global normothermic (37 degrees C) ischemia and 60 min reperfusion. Control hearts exhibited 45+/-2% recovery of pre-ischemic left ventricular developed pressure (LVDP) compared to bisindolylmaleimide- (73+/-7%) and chelerythrine-treated hearts (70+/-11%). Bisindolylmaleimide and cherythrine reduced infarct size from a control value of 24+/-4...Continue Reading

Citations

Sep 29, 2011·Naunyn-Schmiedeberg's Archives of Pharmacology·Kerry-Anne A PerkinsLindon H Young
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