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Cellular and Subcellular Mechanisms of Ventricular Mechano-Arrhythmogenesis

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Cardiac Mechanobiology in Physiology and Disease

Part of the book series: Cardiac and Vascular Biology ((Abbreviated title: Card. vasc. biol.,volume 9))

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Abstract

Intrinsic regulation of cardiac electrical and mechanical activity allows the heart to adjust its function to meet the metabolic demand of the body. This includes the acute feedback of cardiac mechanics to electrics (‘mechano-electric coupling’, MEC), which is achieved primarily through cellular and subcellular elements, including mechano-sensitive ion channels, biophysical signal transmitters and mechano-sensitive biochemical signalling pathways. While MEC is normally involved in fine-tuning of cardiac function, in disease states characterised by perturbations in the cardiac mechanical environment, myocardial mechanics or elements of MEC, it can instead drive arrhythmogenic changes in electrophysiology (‘mechano-arrhythmogenesis’), which can result in sustained ventricular tachyarrhythmias. This chapter briefly reviews essential aspects of MEC, discusses clinical evidence and experimental studies of ventricular mechano-arrhythmogenesis and describes the underlying cellular and subcellular elements involved. It then puts mechano-arrhythmogenesis into a clinical context by focussing on two pathological states that highlight the spatio-temporal dependence of mechano-arrhythmogenesis in the whole heart: one that is characterised by acute, local changes in cardiac electro-mechanics and MEC (acute regional myocardial ischaemia) and one that involves chronic, global changes (hypertension). Overall, an improved understanding of the mechanisms driving ventricular mechano-arrhythmogenesis is critical for the development of anti-arrhythmic therapies targeting MEC, such as modulation of tissue mechanics or alteration of subcellular mechano-sensitive components.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada

    Breanne A. Cameron & T. Alexander Quinn

  2. Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg, Bad Krozingen and Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Breanne A. Cameron & Peter Kohl

  3. Faculty of Engineering, University of Freiburg, Freiburg, Germany

    Peter Kohl

  4. School of Biomedical Engineering, Dalhousie University, Halifax, Canada

    T. Alexander Quinn

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  1. Breanne A. Cameron
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  2. Peter Kohl
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Correspondence to T. Alexander Quinn .

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Editors and Affiliations

  1. Department of Cardiovascular Physiology, Heidelberg University, Heidelberg, Germany

    Markus Hecker

  2. Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    Dirk J. Duncker

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This work was supported by the Canadian Institutes of Health Research (MOP 342562 to T.A.Q.), the Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-04879 to T.A.Q.) and the Heart and Stroke Foundation of Canada (National New Investigator Award to T.A.Q.). BAC and PK are members of the German Research Foundation Collaborative Research Centre SFB1425 (422681845).

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All authors declare they have no conflict of interest.

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Cameron, B.A., Kohl, P., Quinn, T.A. (2023). Cellular and Subcellular Mechanisms of Ventricular Mechano-Arrhythmogenesis. In: Hecker, M., Duncker, D.J. (eds) Cardiac Mechanobiology in Physiology and Disease. Cardiac and Vascular Biology, vol 9. Springer, Cham. https://doi.org/10.1007/978-3-031-23965-6_11

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