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The role of mitochondrial and sarcolemmal K(ATP) channels in canine ethanol-induced preconditioning in vivo. Anesth Analg 2002 Apr;94(4):841-8, table of contents

Date

03/28/2002

Pubmed ID

11916782

DOI

10.1097/00000539-200204000-00012

Abstract

UNLABELLED: Chronic consumption of small doses of ethanol protects myocardium from ischemic injury. We tested the hypothesis that mitochondrial and sarcolemmal adenosine triphosphate-dependent potassium (K(ATP)) channels mediate these beneficial effects. Dogs (n = 76) were fed with ethanol (1.5 g/kg) or water mixed with dry food bid for 6 or 12 wk, fasted overnight before experimentation, and instrumented for measurement of hemodynamics. Dogs received intracoronary saline (vehicle), 5-hydroxydecanoate (a mitochondrial K(ATP) channel antagonist; 6.75 mg/kg over 45 min), or HMR-1098 (a sarcolemmal K(ATP) channel antagonist; 45 microg/kg over 45 min) and were subjected to a 60 min coronary artery occlusion followed by 3 h of reperfusion. A final group of dogs was pretreated with ethanol and chow for 6 wk before occlusion and reperfusion. Myocardial infarct size and transmural coronary collateral blood flow were measured with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. The area at risk of infarction was similar between groups. A 12-wk pretreatment with ethanol significantly reduced infarct size to 13% +/- 2% (mean +/- SEM; n = 8) of the area at risk compared with control experiments (25% +/- 2%; n = 8), but a 6-wk pretreatment did not (21% +/- 2%; n = 8). 5-hydroxydecanoate and HMR-1098 abolished the protective effects of 12-wk ethanol pretreatment (24% +/- 2% and 29% +/- 3%, respectively; n = 8 for each group) but had no effect in dogs that did not receive ethanol (22% +/- 2% and 23% +/- 4%, respectively; n = 8 for each group). No differences in hemodynamics or transmural coronary collateral blood flow were observed between the groups. The results indicate that mitochondrial and sarcolemmal K(ATP) channels mediate ethanol-induced preconditioning in dogs independent of alterations in systemic hemodynamics or coronary collateral blood flow.

IMPLICATIONS: Mitochondrial and sarcolemmal K(ATP) channels mediate ethanol-induced preconditioning independent of alterations in systemic hemodynamics or coronary collateral perfusion in vivo.

Author List

Pagel PS, Krolikowski JG, Kehl F, Mraovic B, Kersten JR, Warltier DC

Author

Paul S. Pagel MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Benzamides
Coronary Circulation
Decanoic Acids
Dogs
Ethanol
Hemodynamics
Hydroxy Acids
Ischemic Preconditioning, Myocardial
Mitochondria, Heart
Myocardial Infarction
Myocardial Reperfusion Injury
Myocardium
Potassium Channel Blockers
Potassium Channels
Sarcolemma
jenkins-FCD Prod-387 b0ced2662056320369de4e5cd5f21c218c03feb3