The Classically Cardioprotective Agent Diazoxide Elicits Arrhythmias in Type 2 Diabetes Mellitus

Journal of the American College of Cardiology
Chaoqin XieFadi G Akar

Abstract

Type 2 diabetes mellitus (T2DM) is associated with an enhanced propensity for ventricular tachyarrhythmias (VTs) under conditions of metabolic demand. Activation of mitochondrial adenosine triphosphate-sensitive potassium (KATP) channels by low-dose diazoxide (DZX) improves hypoglycemia-related complications, metabolic function, and triglyceride and free fatty acid levels and reverses weight gain in T2DM. In this study, we hypothesized that DZX prevents ischemia-mediated arrhythmias in T2DM via its putative cardioprotective and antidiabetic property. Zucker obese diabetic fatty (ZO) rats (n = 43) with T2DM were studied. Controls consisted of Zucker lean (ZL; n = 13) and normal Sprague-Dawley (SprD; n = 30) rats. High-resolution optical action potential mapping was performed before and during challenge with no-flow ischemia for 12 min. Electrophysiological properties were relatively stable in T2DM hearts at baseline. In contrast, ischemia uncovered major differences between groups, because action potential duration (APD) in T2DM failed to undergo progressive adaptation to ischemic challenge. DZX promoted the incidence of arrhythmias, because all DZX-treated T2DM hearts exhibited ischemia-induced VTs that persisted on reperfusion...Continue Reading

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Citations

Sep 5, 2015·Journal of the American College of Cardiology·Blake W Nelson, David R Van Wagoner
Feb 19, 2017·Bioorganic & Medicinal Chemistry Letters·Li-She GanJie Li
Dec 29, 2015·Molecular Medicine Reports·Zhongwei LiuJunkui Wang
Dec 15, 2015·Physiological Reviews·Monique N Foster, William A Coetzee
Jan 1, 2019·Journal of Cellular and Molecular Medicine·Peng YeShao-Liang Chen

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