Christopher H Fry1, Rosaire P Gray2, Paramdeep S Dhillon2, Rita I Jabr2, Emmanuel Dupont2, Pravina M Patel2, Nicholas S Peters2. 1. From the School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, United Kingdom (C.H.F.); Department of Cardiovascular Medicine, Whittington Hospital, London, United Kingdom (R.P.G.); Department of Cardiology, Ashford and St Peter's NHS Foundation Trust, Chertsey, United Kingdom (P.S.D.); Department of Biochemistry and Physiology, University of Surrey, Surrey, United Kingdom (R.I.J.); and Myocardial Function Section, Imperial College London, London, United Kingdom (E.D., P.M.P., N.S.P.). chris.fry@bristol.ac.uk. 2. From the School of Physiology, Pharmacology, and Neuroscience, University of Bristol, Bristol, United Kingdom (C.H.F.); Department of Cardiovascular Medicine, Whittington Hospital, London, United Kingdom (R.P.G.); Department of Cardiology, Ashford and St Peter's NHS Foundation Trust, Chertsey, United Kingdom (P.S.D.); Department of Biochemistry and Physiology, University of Surrey, Surrey, United Kingdom (R.I.J.); and Myocardial Function Section, Imperial College London, London, United Kingdom (E.D., P.M.P., N.S.P.).
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.
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.
Authors: Ana Ortega; Estefanía Tarazón; Carolina Gil-Cayuela; María García-Manzanares; Luis Martínez-Dolz; Francisca Lago; José Ramón González-Juanatey; Juan Cinca; Esther Jorge; Manuel Portolés; Esther Roselló-Lletí; Miguel Rivera Journal: PLoS One Date: 2017-09-21 Impact factor: 3.240