Species-dependent mechanisms of cardiac arrhythmia: A cellular focus

Andrew G. Edwards, William E. Louch

Research output: Contribution to journalReview article

17 Scopus citations

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.

Original languageEnglish (US)
JournalClinical Medicine Insights: Cardiology
Volume11
DOIs
StatePublished - Feb 2 2017
Externally publishedYes

Keywords

  • Arrhythmia
  • Cardiomyocyte
  • Electrophysiology
  • Species

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Species-dependent mechanisms of cardiac arrhythmia: A cellular focus'. Together they form a unique fingerprint.

  • Cite this