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

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.

Unlocking data sets by calibrating populations of models to data density: A study in atrial electrophysiology

“…These calibrated POMs have been used to great effect, including suggesting modifications to existing models of rabbit ventricular ( 15 ) and human atrial cells ( 16 ) required to reproduce specific data; determining the electrophysiological properties that lead to the dangerous phenomena of alternans ( 17 , 18 ), repolarization abnormalities ( 19 ), and atrial fibrillation ( 20 ); and characterizing the sources of the differing function of failing hearts ( 21 ). The technique has also been used to explore the variable response of a population to antiarrhythmic drug treatments ( 7 , 22 , 23 ), to the onset of ischemia in rabbits ( 24 ), and to the effects of hypertrophic cardiomyopathy ( 25 ). Most relevant to our work, calibrated POMs were used by Sánchez et al ( 26 ) to explore the differences between patients exhibiting sinus rhythm (SR) or chronic atrial fibrillation (cAF).…”

Bridging Organ- and Cellular-Level Behavior in Ex Vivo Experimental Platforms Using Populations of Models of Cardiac Electrophysiology

“…The general contention in every study involving populations of cardiac electrophysiology models is that action potential variability is a consequence of changes in the magnitude of the ionic currents that produce the AP, as opposed to a change in their underlying dynamics [8]. Therefore, a population of models (PoM) was generated here by varying all the peak conductances and maximal currents in the TP06 model, these parameters are listed in the literature [14].…”

“…The inverse problem, however, is much more complicated since it is both ill-posed and highly sensitive to intersubject variability [7]. An additional complication is that models for cardiac electrophysiology are based mainly on averaged responses which represent the most common case; a consequential limitation is that, in their existing form, model predictions cannot discriminate pathological behavior from normal physiological variability [8]. Notwithstanding, "experimentally calibrated populations of models" (ePoM) [9][10][11][12] is a promising recent development that includes the effects of variability in the model parameters.…”

Electron tomography of rabbit cardiomyocyte three-dimensional ultrastructure

“…Please see also related communications in this issue by Quinn and Kohl (2016) and Gemmel et al (2016) .…”