title: Mechanistic insights into hypothermic ventricular fibrillation: the role of temperature and tissue size.
abstract: OBJECTIVE
  Hypothermia is well known to be pro-arrhythmic, yet it has beneficial effects as a resuscitation therapy and valuable during intracardiac surgeries. Therefore, we aim to study the mechanisms that induce fibrillation during hypothermia. A better understanding of the complex spatiotemporal dynamics of heart tissue as a function of temperature will be useful in managing the benefits and risks of hypothermia.
  
  
  RESULTS
  We perform two-dimensional numerical simulations by using a minimal model of cardiac action potential propagation fine-tuned on experimental measurements. The model includes thermal factors acting on the ionic currents and the gating variables to correctly reproduce experimentally recorded restitution curves at different temperatures. Simulations are implemented using WebGL, which allows long simulations to be performed as they run close to real time. We describe (i) why fibrillation is easier to induce at low temperatures, (ii) that there is a minimum size required for fibrillation that depends on temperature, (iii) why the frequency of fibrillation decreases with decreasing temperature, and (iv) that regional cooling may be an anti-arrhythmic therapy for small tissue sizes however it may be pro-arrhythmic for large tissue sizes.
  
  
  CONCLUSIONS
  Using a mathematical cardiac cell model, we are able to reproduce experimental observations, quantitative experimental results, and discuss possible mechanisms and implications of electrophysiological changes during hypothermia.
authors.affiliation: Nonlinear Physics and Mathematical Modeling Laboratory, University Campus Bio-Medico of Rome, Via A. del Portillo 21, I-00128 Rome, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Filippi
authors.forename: Alessio
authors.initials: A
authors.lastname: Gizzi
authors.forename: Christian
authors.initials: C
authors.lastname: Cherubini
authors.forename: Stefan
authors.initials: S
authors.lastname: Luther
authors.forename: Flavio H
authors.initials: FH
authors.lastname: Fenton
mesh_terms: D000818:Animals; D001831:Body Temperature; D003198:Computer Simulation; D006329:Heart Conduction System / Q000473:pathology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007035:Hypothermia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000473:pathology; D009929:Organ Size; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*
keywords: Cardiac dynamics; Reaction-diffusion equations; Spiral breakup; Thermoelectric model