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Architectural Correlates of Myocardial Conduction: Changes to the Topography of Cellular Coupling, Intracellular Conductance and Action Potential Propagation with Hypertrophy in Guinea-Pig Ventricular Myocardium.

Fry, CH, Gray, RP, Dhillon, PS, Jabr, RI, Dupont, E, Patel, PM and Peters, NS (2014) Architectural Correlates of Myocardial Conduction: Changes to the Topography of Cellular Coupling, Intracellular Conductance and Action Potential Propagation with Hypertrophy in Guinea-Pig Ventricular Myocardium. Circulation: Arrhythmia and Electrophysiology, 7. pp. 1198-1204.

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Abstract

Background—We tested the hypothesis that alterations to action potential conduction velocity (CV) and conduction anisotropy in left ventricular hypertrophy are associated with topographical changes to gap-junction coupling and intracellular conductance by measuring these variables in the same preparations. Methods and Results—Left ventricular papillary muscles were excised from aortic-banded or sham-operated guinea-pig hearts. With intracellular stimulating and recording microelectrodes, CV was measured in 3 dimensions with simultaneous conductance mapping with subthreshold stimuli and correlated with quantitative histomorphometry of myocardial architecture and connexin 43 distribution. In hypertrophied myocardium, CV in the longitudinal axis was smaller and transverse velocity was greater compared with control; associated with similar differences of intracellular conductance, consistent with more cell contacts per cell (5.7±0.2 versus 8.1±0.5; control versus hypertrophy), and more intercalated disks mediating side-to-side coupling (8.2±0.2 versus 10.2±0.4 per cell). Intercalated disk morphology and connexin 43 immunolabelling were not different in hypertrophy. Hypertrophied preparations showed local submillimeter (≈250 μm) regions with slow conduction and low intracellular conductance, which, although not affecting CV on the millimeter scale, were consistent with discontinuities from increased microscopical connective tissue content. Conclusions—With myocardial hypertrophy, altered longitudinal and transverse CV, and greater nonuniformity of CV anisotropy correspond to changes of intracellular conductance. These are associated with alteration of myocardial architecture, specifically the topography of cell–cell coupling and gap-junction connectivity.

Item Type: Article
Subjects : Medical Science
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
AuthorsEmailORCID
Fry, CHUNSPECIFIEDUNSPECIFIED
Gray, RPUNSPECIFIEDUNSPECIFIED
Dhillon, PSUNSPECIFIEDUNSPECIFIED
Jabr, RIUNSPECIFIEDUNSPECIFIED
Dupont, EUNSPECIFIEDUNSPECIFIED
Patel, PMUNSPECIFIEDUNSPECIFIED
Peters, NSUNSPECIFIEDUNSPECIFIED
Date : 13 October 2014
Identification Number : https://doi.org/10.1161/CIRCEP.114.001471
Copyright Disclaimer : © 2014 American Heart Association, Inc.
Uncontrolled Keywords : action potential, arrhythmia (mechanisms), conduction velocity, connexin43, gap junctions, intracellular conductance, left ventricular hypertrophy
Depositing User : Symplectic Elements
Date Deposited : 13 Sep 2016 14:36
Last Modified : 13 Sep 2016 14:36
URI: http://epubs.surrey.ac.uk/id/eprint/806784

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