A condition for setting off ectopic waves in computational models of excitable cells.
The purpose of this paper is to study the stability of steady state solutions of the Monodomain model equipped with Luo-Rudy I kinetics. It is well established that re-entrant arrhythmias can be created in computational models of excitable cells. Such arrhythmias can be initiated by applying an external stimulus that interacts with a partially refractory region, and spawn breaking waves that can eventually generate extremely complex wave patterns commonly referred to as fibrillation. An ectopic wave is one possible stimulus that may initiate fibrillation. Physiologically, it is well known that ectopic waves exist, but the mechanism for initiating ectopic waves in a large collection of cells is poorly understood. In the present paper we consider computational models of collections of excitable cells in one and two spatial dimensions. The cells are modeled by Luo-Rudy I kinetics, and we assume that the spatial dynamics is governed by the Monodomain model. The mathematical analysis is carried out for a reduced model that is known to provide good approximations of the initial phase of solutions of the Luo-Rudy I model. A further simplification is also introduced to motivate and explain the results for the more complicated models. In the analysis the cells are divided into two regions; one region (N) consists of normal cells as model by the standard Luo-Rudy I model, and another region (A) where the cells are automatic in the sense that they would act as pacemaker cells if they where isolated from their surroundings. We let delta denote the spatial diffusion and a denote a characteristic length of the automatic region. It has previously been shown that reducing diffusion or increasing the automatic region enhances ectopic activity. Here we derive a condition for the transition from stable resting state to ectopic wave spread. Under suitable assumptions on the model we provide mathematical and computational arguments indicating that there is a constant eta such that a steady state solution of this system is stable whenever delta approximately > etaa(2), and unstable whenever delta approximately < etaa(2).
Center for Biomedical Computing, Simula Research Laboratory, P.O. Box 134, 1325 Lysaker, Norway. aslak@simula.no
Aslak
A
Tveito
Glenn T
GT
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D000200:Action Potentials; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000503:physiopathology; D002450:Cell Communication; D004553:Electric Conductivity; D004558:Electric Stimulation; D022062:Electrophysiologic Techniques, Cardiac; D006329:Heart Conduction System / Q000503:physiopathology; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000378:metabolism; D009716:Numerical Analysis, Computer-Assisted; D049490:Systems Biology / Q000379:methods