A quantitative comparison of the behavior of human ventricular cardiac electrophysiology models in tissue

PLoS One. 2014 Jan 8;9(1):e84401. doi: 10.1371/journal.pone.0084401. eCollection 2014.

Abstract

Numerical integration of mathematical models of heart cell electrophysiology provides an important computational tool for studying cardiac arrhythmias, but the abundance of available models complicates selecting an appropriate model. We study the behavior of two recently published models of human ventricular action potentials, the Grandi-Pasqualini-Bers (GPB) and the O'Hara-Virág-Varró-Rudy (OVVR) models, and compare the results with four previously published models and with available experimental and clinical data. We find the shapes and durations of action potentials and calcium transients differ between the GPB and OVVR models, as do the magnitudes and rate-dependent properties of transmembrane currents and the calcium transient. Differences also occur in the steady-state and S1-S2 action potential duration and conduction velocity restitution curves, including a maximum conduction velocity for the OVVR model roughly half that of the GPB model and well below clinical values. Between single cells and tissue, both models exhibit differences in properties, including maximum upstroke velocity, action potential amplitude, and minimum diastolic interval. Compared to experimental data, action potential durations for the GPB and OVVR models agree fairly well (although OVVR epicardial action potentials are shorter), but maximum slopes of steady-state restitution curves are smaller. Although studies show alternans in normal hearts, it occurs only in the OVVR model, and only for a narrow range of cycle lengths. We find initiated spiral waves do not progress to sustained breakup for either model. The dominant spiral wave period of the GPB model falls within clinically relevant values for ventricular tachycardia (VT), but for the OVVR model, the dominant period is longer than periods associated with VT. Our results should facilitate choosing a model to match properties of interest in human cardiac tissue and to replicate arrhythmia behavior more closely. Furthermore, by indicating areas where existing models disagree, our findings suggest avenues for further experimental work.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials
  • Calcium / metabolism
  • Cell Membrane / metabolism
  • Electrophysiological Phenomena*
  • Glucans / metabolism
  • Heart Conduction System / cytology
  • Heart Conduction System / pathology
  • Heart Conduction System / physiology
  • Heart Conduction System / physiopathology
  • Heart Ventricles / cytology*
  • Heart Ventricles / metabolism
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Humans
  • Models, Cardiovascular*
  • Tachycardia / metabolism
  • Tachycardia / pathology
  • Tachycardia / physiopathology
  • Ventricular Function*

Substances

  • Glucans
  • alternan
  • Calcium

Grants and funding

This study was supported by the Libyan-North American Scholarship Program from the Ministry of Higher Education and Scientific Research in Libya (M.M.E). This material is based upon work supported by the National Science Foundation under Grant Number CMMI-1028261 (E.M.C.) and the research leading to the results has received funding from the European Community's Seventh Framework Program FP7/20072013 under grant agreement No. HEALTH-F2-2009-241526, EUTrigTreat (E.M.C.). This work used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number OCI-1053575. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.