Acute alcohol-induced protection against infarction in rabbit hearts: differences from and similarities to ischemic preconditioning.
Recent studies reveal that brief ethanol exposure induces cardioprotection against simulated ischemia in cardiomyocytes by the activation of protein kinase C- epsilon. The present study tests the ability of ethanol to induce protection in rabbit hearts in which infarct size was the end-point and explores the signal transduction pathways involved. In isolated rabbit hearts, 50 m m ethanol infused for 5 min with 10 min of washout prior to 30 min of regional ischemia reduced infarct size (triphenyltetrazolium chloride staining) by 49%. Neither adenosine receptor blockade with 8-(p -sulfophenyl) theophylline nor the free radical scavenger N-2-mercaptopropionyl glycine inhibited the protection triggered by ethanol. In contrast, protein kinase C inhibition with chelerythrine, protein tyrosine kinase inhibition with genistein, and blockade of ATP-sensitive potassium channels (K(ATP)) with either 5-hydroxydecanoate or glibenclamide did abolish protection. Thus, transient ethanol exposure followed by washout prior to ischemia elicits a preconditioning-like effect involving protein kinase C, at least one protein tyrosine kinase, and K(ATP)channels, but neither adenosine nor free radicals.
Krenz
M
M
Department of Physiology, University of South Alabama, Mobile, AL 36688, USA.
Baines
C P
CP
Heusch
G
G
Downey
J M
JM
Cohen
M V
MV
D000255:Adenosine Triphosphate / Q000378:metabolism; D000438:Alcohols / Q000494:pharmacology*; D000470:Alkaloids; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D053119:Benzophenanthridines; D003652:Decanoic Acids / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D007527:Isoenzymes / Q000378:metabolism; D009203:Myocardial Infarction / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051744:Protein Kinase C-epsilon; D011817:Rabbits; D051381:Rats; D015398:Signal Transduction; D013997:Time Factors
D000438:Alcohols; D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D053119:Benzophenanthridines; D003652:Decanoic Acids; D004791:Enzyme Inhibitors; D006880:Hydroxy Acids; D007527:Isoenzymes; D010617:Phenanthridines; D015221:Potassium Channels; D000431:Ethanol; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D019833:Genistein; C016299:chelerythrine; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D005905:Glyburide