Abstract 72: Akt Activation Stimulated by Moderate Alcohol Consumption is Critical for Enhancement of Mitochondrial Function and Cardiac Contractile Recovery Following Ischemia-reperfusion

Abstract
Background: Moderate alcohol consumption induces protection against myocardial reperfusion injury and upregulation of protein kinase B (Akt) expression and kinase activity in heart tissue. However, it is unclear whether Akt activation is required for ethanol-mediated cardioprotection.
Hypothesis: Akt activation induced by moderate alcohol consumption preserves mitochondrial function and improves cardiac contractile recovery during oxidative stress.
Methods: Perfused hearts from C57Bl/6 mice fed 10% ethanol (vol/vol) as drinking water for 16 weeks (E) and age-matched controls (C) were subjected to 25 min global ischemia and 30 min reperfusion. Hearts were treated with phosphatidylinositol 3′-kinase inhibitor wortmannin (10 nM) throughout each protocol to prevent Akt activation. State 3 oxygen consumption rates (OCR), respiratory control ratios (RCR), and aconitase activity were assayed in mitochondria following 30 min reperfusion. Akt phosphorylation density unit and malondialdehyde (MDA) concentrations were assayed in heart extracts.
Results: Wortmannin (W) had no effect on the baseline hemodynamic function of either group. However, Akt inhibition blocked protective effects of moderate ethanol intake on mitochondrial respiration and Krebs cycle intermediates after ischemia-reperfusion (Table⇓). Akt inhibition also worsened lipid peroxidation and contractile abnormalities in hearts from ethanol-treated animals.
Conclusions:
Moderate alcohol consumption improves cardiac metabolism and contractility during the stress of ischemia-reperfusion.
Akt activation is required for the sustained benefits of moderate ethanol exposure, in large part by preventing oxidative injury to heart mitochondria.

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- Abstract 72: Akt Activation Stimulated by Moderate Alcohol Consumption is Critical for Enhancement of Mitochondrial Function and Cardiac Contractile Recovery Following Ischemia-reperfusionHui-Zhong Zhou, Xiaokui Ma, Gary Cecchini, Ursula Simonis and Mary O GrayCirculation. 2006;114:II_1202-II_1203, originally published December 17, 2015
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- Abstract 72: Akt Activation Stimulated by Moderate Alcohol Consumption is Critical for Enhancement of Mitochondrial Function and Cardiac Contractile Recovery Following Ischemia-reperfusionHui-Zhong Zhou, Xiaokui Ma, Gary Cecchini, Ursula Simonis and Mary O GrayCirculation. 2006;114:II_1202-II_1203, originally published December 17, 2015