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The Effect of Inhibition of Glycolysis on Susceptibility to Ischemia‐Induced Ventricular Fibrillation in the Isolated Rat Heart
Author(s) -
ClementsJewery Hugh,
Endler Graham
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.798.9
Subject(s) - glycolysis , ventricular fibrillation , cardiology , ischemia , medicine , fibrillation , atrial fibrillation , metabolism
Ventricular fibrillation (VF) is a major cause of sudden cardiac death but the triggers of VF in myocardial ischemia are poorly understood. We have previously proposed that ATP depletion may be the major trigger for development of VF in myocardial ischemia due to the consequent ionic and electrical dysfunction that creates an arrhythmogenic substrate. In the present study we determined the importance of ATP supplied by glycolysis to development of ischemia‐induced VF by examining the effect of inhibition of glycolysis on the incidence and onset of VF. Isolated rat hearts (n=12 per group) were perfused in the Langendorff mode with modified Krebs solution, and then switched in randomized and blinded manner to one of three test solutions: Glucose Control (Krebs containing glucose + vehicle), Pyruvate Control (Krebs containing pyruvate + vehicle) or Pyrvuate + IAA (Krebs containing pyruvate + 100μM sodium iodoacetate, an irreversible inhibitor of glycolysis). After 15 min of perfusion with test solution, regional ischemia was induced by coronary occlusion and maintained for 30 minutes. Arrhythmias were determined from the ECG. The incidence of VF was 83%, 42% and 67% in the glucose control, pyruvate control and pyruvate + IAA groups respectively (P=NS). The mean time to onset of VF was 832±67 s, 823±76 s, and 671±67 s in the glucose control, pyruvate control and pyruvate + IAA groups respectively (P=NS). Thus, inhibition of glycolysis with pyruvate + IAA increased VF incidence and shortened the time to VF as a trend. We are increasing group size in order to avoid a Type II error when evaluating the effect of glycolytic inhibition on VF susceptibility. Supported by a Scientist Development Grant from the American Heart Association.