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Clin Med Insights Cardiol. 2017 Feb 2;11:1179546816686061. doi: 10.1177/1179546816686061. eCollection 2017.

Species-Dependent Mechanisms of Cardiac Arrhythmia: A Cellular Focus.

Author information

1
Center for Biomedical Computing, Simula Research Laboratory, Lysaker, Norway.
2
Center for Cardiological Innovation, Simula Research Laboratory, Lysaker, Norway.
3
Department of Biosciences, University of Oslo, Oslo, Norway.
4
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
5
K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.

Abstract

Although ventricular arrhythmia remains a leading cause of morbidity and mortality, available antiarrhythmic drugs have limited efficacy. Disappointing progress in the development of novel, clinically relevant antiarrhythmic agents may partly be attributed to discrepancies between humans and animal models used in preclinical testing. However, such differences are at present difficult to predict, requiring improved understanding of arrhythmia mechanisms across species. To this end, we presently review interspecies similarities and differences in fundamental cardiomyocyte electrophysiology and current understanding of the mechanisms underlying the generation of afterdepolarizations and reentry. We specifically highlight patent shortcomings in small rodents to reproduce cellular and tissue-level arrhythmia substrate believed to be critical in human ventricle. Despite greater ease of translation from larger animal models, discrepancies remain and interpretation can be complicated by incomplete knowledge of human ventricular physiology due to low availability of explanted tissue. We therefore point to the benefits of mathematical modeling as a translational bridge to understanding and treating human arrhythmia.

KEYWORDS:

arrhythmia; cardiomyocyte; electrophysiology; species

Conflict of interest statement

DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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