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 to 8+/-2 and 9+/-3%, respectively. Preconditioning isolated hearts with 5 min ischemia and 10 min reperfusion prior to prolonged ischemia reduced infarct size to 10.4+/-2.3%, an effect which was blocked by chelerythrine (22.5+/-4.2% infarct size). These results suggest that although PKC may play a role in ischemic preconditioning, PKC inhibitors can be cardioprotective during prolonged ischemia.
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Authors | R D Lasley, M A Noble, R M Mentzer Jr |
Journal | Journal of molecular and cellular cardiology
(J Mol Cell Cardiol)
Vol. 29
Issue 12
Pg. 3345-56
(Dec 1997)
ISSN: 0022-2828 [Print] England |
PMID | 9441840
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Copyright | Copyright 1997 Academic Press Limited. |
Chemical References |
- Alkaloids
- Benzophenanthridines
- Enzyme Inhibitors
- Indoles
- Maleimides
- Phenanthridines
- Purines
- chelerythrine
- Protein Kinase C
- bisindolylmaleimide
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Topics |
- Alkaloids
- Animals
- Benzophenanthridines
- Enzyme Inhibitors
(pharmacology)
- Female
- In Vitro Techniques
- Indoles
(pharmacology)
- Ischemic Preconditioning, Myocardial
- Male
- Maleimides
(pharmacology)
- Myocardial Infarction
(enzymology)
- Myocardium
(enzymology)
- Phenanthridines
(pharmacology)
- Protein Kinase C
(antagonists & inhibitors)
- Purines
(metabolism)
- Rabbits
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