The effect of activation sequence on transmural patterns of repolarization and action potential duration in rabbit ventricular myocardium

Myles, R.C. , Bernus, O., Burton, F.L., Cobbe, S.M. and Smith, G.L. (2010) The effect of activation sequence on transmural patterns of repolarization and action potential duration in rabbit ventricular myocardium. American Journal of Physiology: Heart and Circulatory Physiology, 289(8), H1812-H1822. (doi: 10.1152/ajpheart.00518.2010)

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Although transmural heterogeneity of action potential duration (APD) is established in single cells isolated from different tissue layers, the extent to which it produces transmural gradients of repolarization in electrotonically coupled ventricular myocardium remains controversial. The purpose of this study was to examine the relative contribution of intrinsic cellular gradients of APD and electrotonic influences to transmural repolarization in rabbit ventricular myocardium. Transmural optical mapping was performed in left ventricular wedge preparations from eight rabbits. Transmural patterns of activation, repolarization, and APD were recorded during endocardial and epicardial stimulation. Experimental results were compared with modeled data during variations in electrotonic coupling. A transmural gradient of APD was evident during endocardial stimulation, which reflected differences previously seen in isolated cells, with the longest APD at the endocardium and the shortest at the epicardium (endo: 165 ± 5 vs. epi: 147 ± 4 ms; P < 0.05). During epicardial stimulation, this gradient reversed (epi: 162 ± 4 vs. endo: 148 ± 6 ms; P < 0.05). In both activation sequences, transmural repolarization followed activation and APD shortened along the activation path such that significant transmural gradients of repolarization did not occur. This correlation between transmural activation time and APD was recapitulated in simulations and varied with changes in intercellular coupling, confirming that it is mediated by electrotonic current flow between cells. These data suggest that electrotonic influences are important in determining the transmural repolarization sequence in rabbit ventricular myocardium and that they are sufficient to overcome intrinsic differences in the electrophysiological properties of the cells across the ventricular wall.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey and Myles, Dr Rachel and Burton, Dr Francis and Cobbe, Professor Stuart
Authors: Myles, R.C., Bernus, O., Burton, F.L., Cobbe, S.M., and Smith, G.L.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:American Journal of Physiology: Heart and Circulatory Physiology
Journal Abbr.:AJP: Heart and circulatory physiology
ISSN (Online):1522-1539
Published Online:01 October 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
496941Cellular basis for alternating T-wave morphology in isolated rabbit heartsGodfrey SmithBritish Heart Foundation (BHF)PG/09/011/26753Institute of Cardiovascular and Medical Sciences