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Combined effects of reduced connexin 43, depressed active generator properties and energetic stress on conduction disturbances in canine failing myocardium

  • Integrative Physiology
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Abstract

To show that reductions in connexin43 (Cx43) can contribute, in association with electrophysiological alterations identified from unipolar recordings, to conduction disturbances in a realistic model of heart failure, canines were subjected to chronic rapid pacing (240/min for 4 weeks) and progressive occlusion of the left coronary circumflex artery (LCx) by an ameroid constrictor. Alterations identified from 191 epicardial recordings included abrupt activation delay, functional block, ST segment potential elevation, and reduced maximum negative slope (−dV/dt max). The LCx territory was divided into apical areas with depressed conduction velocity (LCx1: 0.06 ± 0.04 m/s, mean ± SD) and basal areas with relatively preserved conduction (LCx2: 0.28 ± 0.01 m/s). Subepicardial Cx43 immunoblot measurements (percent of corresponding healthy heart measurements) were reduced in LCx1 (∼40%) and LCx2 (∼60%). In addition, −dV/dt max was significantly depressed (−3.8 ± 3.3 mV/ms) and ST segment potential elevated (23.3 ± 14.6 mV) in LCx1 compared to LCx2 (−9.5 ± 3.4 mV/ms and 0.3 ± 1.4 mV). Anisotropic conduction, Cx43 and ST segment potential measurements from the left anterior descending coronary artery territory, and interstitial collagen from all regions were similar to the healthy. Thus, moderate Cx43 reduction to “clinically relevant” levels can, in conjunction with regional energetic stress and depression of sarcolemmal active generator properties, provide a substrate for conduction disturbances.

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Acknowledgments

The financial support of the Canadian Institutes of Health Research and Heart and Stroke Foundation of Québec for this investigation is gratefully acknowledged. None of the authors have any competing financial interest related to this study.

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Authors and Affiliations

  1. Centre de recherche, Hôpital du Sacré-Cœur de Montréal, 5400 Gouin Blvd. West, Montréal, H4J 1C5, Québec, Canada

    Stéphanie Falcao, Guy Rousseau, Ghayath Baroudi, Michel Vermeulen, Caroline Bouchard & René Cardinal

  2. Département de pharmacologie, Faculté de médecine, Université de Montréal, Montréal, Québec, Canada

    Stéphanie Falcao, Guy Rousseau, Ghayath Baroudi & René Cardinal

  3. Departments of Physiology & Pharmacology and Medicine, University of Western Ontario, London, Ontario, Canada

    Douglas L. Jones

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  1. Stéphanie Falcao
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Correspondence to René Cardinal.

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Falcao, S., Rousseau, G., Baroudi, G. et al. Combined effects of reduced connexin 43, depressed active generator properties and energetic stress on conduction disturbances in canine failing myocardium. Pflugers Arch - Eur J Physiol 454, 999–1009 (2007). https://doi.org/10.1007/s00424-007-0266-7

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