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

doi:10.1016/j.pbiomolbio.2016.06.003

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

Medicine

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	169-184
Number of pages	16
Journal	Progress in Biophysics and Molecular Biology
Volume	121
Issue number	2
DOIs	https://doi.org/10.1016/j.pbiomolbio.2016.06.003
Publication status	Published - Jul 1 2016

Bibliographical note

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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10.1016/j.pbiomolbio.2016.06.003

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Rabbit-specific computational modelling of ventricular cell electrophysiology: Using populations of models to explore variability in the response to ischemia. / Gemmell, Philip; Burrage, Kevin; Rodríguez, Blanca et al.
In: Progress in Biophysics and Molecular Biology, Vol. 121, No. 2, 01.07.2016, p. 169-184.

Research output: Contribution to journal › Article › peer-review

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

Abstract

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