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.
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