Rabbit-specific computational modelling of ventricular cell electrophysiology: Using populations of models to explore variability in the response to ischemia

Philip Gemmell, Kevin Burrage, Blanca Rodríguez, T. Alexander Quinn

Résultat de recherche: Articleexamen par les pairs

22 Citations (Scopus)

Résumé

Computational modelling, combined with experimental investigations, is a powerful method for investigating complex cardiac electrophysiological behaviour. The use of rabbit-specific models, due to the similarities of cardiac electrophysiology in this species with human, is especially prevalent. In this paper, we first briefly review rabbit-specific computational modelling of ventricular cell electrophysiology, multi-cellular simulations including cellular heterogeneity, and acute ischemia. This mini-review is followed by an original computational investigation of variability in the electrophysiological response of two experimentally-calibrated populations of rabbit-specific ventricular myocyte action potential models to acute ischemia. We performed a systematic exploration of the response of the model populations to varying degrees of ischemia and individual ischemic parameters, to investigate their individual and combined effects on action potential duration and refractoriness. This revealed complex interactions between model population variability and ischemic factors, which combined to enhance variability during ischemia. This represents an important step towards an improved understanding of the role that physiological variability may play in electrophysiological alterations during acute ischemia.

Langue d'origineEnglish
Pages (de-à)169-184
Nombre de pages16
JournalProgress in Biophysics and Molecular Biology
Volume121
Numéro de publication2
DOI
Statut de publicationPublished - juill. 1 2016

Note bibliographique

Funding Information:
The authors would like to thank Dr. Alfonso Bueno-Orovio (Dept. of Computer Science, University of Oxford) for helpful discussions about the manuscript. Financial support was provided by an Engineering and Physical Sciences Research Council doctoral scholarship to PG (EP/G03706X/1), a Wellcome Trust Senior Research fellowship in Basic Biomedical Sciences to BR ( 100246/Z/12/Z ), and by operating grants from the Canadian Institutes of Health Research ( MOP-142424 ), the Natural Sciences and Engineering Research Council of Canada ( RGPIN-2016-04879 ), and the Nova Scotia Health Research Foundation ( MED-EST-2014-9582 ) to TAQ.

Publisher Copyright:
© 2016 The Authors

ASJC Scopus Subject Areas

  • Biophysics
  • Molecular Biology

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