Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs

Chaoqin Xie, Nora Biary, Carlo G. Tocchetti, Miguel A. Aon, Nazareno Paolocci, Justin Kauffman, Fadi G. Akar

Research output: Contribution to journalArticle

Abstract

Chronic hyperglycemia in type-1 diabetes mellitus is associated with oxidative stress (OS) and sudden death. Mechanistic links remain unclear. We investigated changes in electrophysiological (EP) properties in a model of chronic hyperglycemia before and after challenge with OS by GSH oxidation and tested reversibility of EP remodeling by insulin. Guinea pigs survived for 1 mo following streptozotocin (STZ) or saline (sham) injection. A treatment group received daily insulin for 2 wk to reverse STZinduced hyperglycemia (STZ + Ins). EP properties were measured using high-resolution optical action potential mapping before and after challenge of hearts with diamide. Despite elevation of glucose levels in STZ compared with sham-operated (P = 0.004) and STZ + Ins (P = 0.002) animals, average action potential duration (APD) and arrhythmia propensity were not altered at baseline. Diamide promoted early (

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume304
Issue number7
DOIs
StatePublished - 2013

Fingerprint

Streptozocin
Glutathione
Guinea Pigs
Hyperglycemia
Diamide
Voltage-Sensitive Dye Imaging
Oxidative Stress
Insulin
Sudden Death
Type 1 Diabetes Mellitus
Action Potentials
Cardiac Arrhythmias
Glucose
Injections
Therapeutics

Keywords

  • Arrhythmias
  • Conduction
  • Electrical remodeling
  • Insulin
  • Oxidative stress
  • Repolarization
  • Type-1 diabetes mellitus

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs. / Xie, Chaoqin; Biary, Nora; Tocchetti, Carlo G.; Aon, Miguel A.; Paolocci, Nazareno; Kauffman, Justin; Akar, Fadi G.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 304, No. 7, 2013.

Research output: Contribution to journalArticle

Xie, Chaoqin ; Biary, Nora ; Tocchetti, Carlo G. ; Aon, Miguel A. ; Paolocci, Nazareno ; Kauffman, Justin ; Akar, Fadi G. / Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs. In: American Journal of Physiology - Heart and Circulatory Physiology. 2013 ; Vol. 304, No. 7.
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