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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
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Maintenance of myocyte volume homeostasis during stress by diazoxide is cardioprotective

Ashraf S Al-Dadah1, Rochus K Voeller, Richard B Schuessler

  • 1Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

The Annals of Thoracic Surgery
|August 28, 2007
PubMed

Insights

Diazoxide effectively prevents myocyte swelling and preserves contractility during metabolic inhibition, independent of ATP-sensitive potassium channels. This suggests a novel mechanism for protecting heart cells from stunning.

Area of Science:

  • Cardiology
  • Cell Physiology
  • Biochemistry

Background:

  • Myocyte swelling and reduced contractility occur during hyperkalemic cardioplegia and hyposmotic stress.
  • Diazoxide, an adenosine triphosphate-sensitive potassium channel (K(ATP)) opener, previously attenuated these effects.
  • The current study investigates diazoxide's impact on metabolic inhibition-induced myocyte changes and explores underlying mechanisms.

Purpose of the Study:

  • To determine the effect of diazoxide on myocyte swelling and contractility following metabolic inhibition.
  • To elucidate the potential mechanisms by which diazoxide exerts its protective effects.

Main Methods:

  • Isolated rabbit myocytes were subjected to metabolic inhibition (using sodium cyanide and 2-deoxyglucose) with or without diazoxide.
  • Specific adenosine triphosphate-sensitive potassium (K(ATP)) channel blockers (HMR1098 and 5-hydroxydeconoate) were used to investigate the role of sarcolemmal and mitochondrial K(ATP) channels.
  • Myocyte volume and contractility were measured before, during, and after the intervention.

Main Results:

  • Metabolic inhibition led to significant myocyte swelling and decreased contractility.
  • Diazoxide completely prevented myocyte swelling and attenuated the reduction in contractility.
  • The protective effects of diazoxide were observed irrespective of the presence of K(ATP) channel blockers.

Conclusions:

  • Diazoxide attenuates myocyte swelling and preserves contractility during metabolic inhibition, independent of K(ATP) channels.
  • These findings suggest a K(ATP)-independent role for diazoxide in maintaining myocyte volume homeostasis.
  • Preventing myocyte swelling improves contractility, supporting the hypothesis that swelling contributes to myocardial stunning.
Abstract

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