title: Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.
abstract: Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.
authors.affiliation: a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.
authors.forename: Kornél
authors.initials: K
authors.lastname: Kistamás
authors.affiliation: a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Hegyi
authors.affiliation: a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Váczi
authors.affiliation: a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.|b Faculty of Pharmacy, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Horváth
authors.affiliation: a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Bányász
authors.affiliation: a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.|d Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Magyar
authors.affiliation: a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.|c Department of Dental Physiology, Faculty of Dentistry, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.
authors.forename: Norbert
authors.initials: N
authors.lastname: Szentandrássy
authors.affiliation: a Department of Physiology, Faculty of Medicine, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.|c Department of Dental Physiology, Faculty of Dentistry, University of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.
authors.forename: Péter P
authors.initials: PP
authors.lastname: Nánási
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D000975:Antioxidants
keywords: action potential duration; beat-to-beat variability; canine myocytes; durée du potentiel d’action; myocytes canins; potentiel redox; redox potential; short term variability; variabilité battement par battement; variabilité à court terme