Rabbit-specific computational modelling of ventricular cell electrophysiology: Using populations of models to explore variability in the response to ischemia.
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.
Department of Computer Science, University of Oxford, Oxford, UK.
Philip
P
Gemmell
Department of Computer Science, University of Oxford, Oxford, UK; School of Mathematical Sciences and ARC Centre of Excellence, ACEMS, Queensland University of Technology, Brisbane, Australia.
Kevin
K
Burrage
Department of Computer Science, University of Oxford, Oxford, UK.
Blanca
B
Rodríguez
Department of Physiology and Biophysics, Dalhousie University, 5850 College St, Lab 3F, Halifax, NS B3H 4R2, Canada; School of Biomedical Engineering, Dalhousie University, 5850 College St, Lab 3F, Halifax, NS B3H 4R2, Canada. Electronic address: alex.quinn@dal.ca.
T Alexander
TA
Quinn
D000200:Action Potentials; D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D055724:Electrophysiological Phenomena; D006352:Heart Ventricles / Q000473:pathology*; D006801:Humans; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000473:pathology* / Q000503:physiopathology*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D013045:Species Specificity
D000255:Adenosine Triphosphate; D011188:Potassium
Cardiac cell electrophysiology; Computational modelling; Ischemia; Populations of models; Rabbit; Variability