Feeding the fibrillating heart: Dichloroacetate improves cardiac contractile dysfunction following VF

American Journal of Physiology. Heart and Circulatory Physiology
Mohammed Ali AzamKumaraswamy Nanthakumar

Abstract

Ventricular fibrillation (VF) is an important cause of sudden cardiac arrest following myocardial infarction. Following resuscitation from VF, decreased cardiac contractile function is a common problem. During and following myocardial ischemia, decreased glucose oxidation, increased anaerobic glycolysis for cardiac energy production are harmful and energetically expensive. The objective of the present study is to determine the effects of dichloroacetate (DCA), a glucose oxidation stimulator, on cardiac contractile dysfunction following ischemia-induced VF. Male Sprague-Dawley rat hearts were Langendorff perfused in Tyrode's buffer. Once stabilized, hearts were subjected to 15 min of global ischemia and 5 min of aerobic reperfusion in the presence or absence of DCA. At the 6th min of reperfusion, VF was induced electrically, and terminated. Left ventricular (LV) pressure was measured using a balloon. Pretreatment with DCA significantly improved post-VF left ventricular developed pressure (LVDP) and dp/dtmax. In DCA-pretreated hearts, post-VF lactate production and pyruvate dehydrogenase (PDH) phosphorylation were significantly reduced, indicative of stimulated glucose oxidation, and inhibited anaerobic glycolysis by activation o...Continue Reading

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Citations

Feb 1, 2018·The Journal of Physiology·Michal K HandzlikMark A Cole
Mar 21, 2017·Circulation. Arrhythmia and Electrophysiology·Mohammed Ali AzamKumaraswamy Nanthakumar
Sep 26, 2017·JACC. Basic to Translational Science·Adam R WendeMartin E Young

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