Alternans and spiral breakup in a human ventricular tissue model
Noble
Penny
Oxford University Cardiac Electrophysiology Group
Model Status
This is the ENDOCARDIAL CELL VARIANT of the model. This model was created by Penny Noble of Oxford University and is known to read in COR and PCEnv. A stimulus protocol has been added that allows the model to simulate multiple action potentials at 1Hz.
Model Structure
ABSTRACT: Ventricular fibrillation (VF) is one of the main causes of death in the Western world. According to one hypothesis, the chaotic excitation dynamics during VF are the result of dynamical instabilities in action potential duration (APD) the occurrence of which requires that the slope of the APD restitution curve exceeds 1. Other factors such as electrotonic coupling and cardiac memory also determine whether these instabilities can develop. In this paper we study the conditions for alternans and spiral breakup in human cardiac tissue. Therefore, we develop a new version of our human ventricular cell model, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics. We apply this model to study the conditions for electrical instability in single cells, for reentrant waves in a ring of cells, and for reentry in two-dimensional sheets of ventricular tissue. We show that an important determinant for the onset of instability is the recovery dynamics of the fast sodium current. Slower sodium current recovery leads to longer periods of spiral wave rotation and more gradual conduction velocity restitution, both of which suppress restitution-mediated instability. As a result, maximum restitution slopes considerably exceeding 1 (up to 1.5) may be necessary for electrical instability to occur. Although slopes necessary for the onset of instabilities found in our study exceed 1, they are within the range of experimentally measured slopes. Therefore, we conclude that steep APD restitution-mediated instability is a potential mechanism for VF in the human heart.
The original paper reference is cited below:
Alternans and spiral breakup in a human ventricular tissue model, K.H.W.J. ten Tusscher, A.V. Panfilov, Sep 2006,
American Journal of Physiology, Heart and Circulatory Physiology, 291 3, H1088-1100. PubMed ID: 16565318
cell diagram
A schematic diagram describing the ion movement across the cell surface membrane and the sarcoplasmic reticulum, which are described by the Ten Tusscher et al. 2006 mathematical model of the human ventricular myocyte.
Alternans and spiral breakup in a human ventricular tissue model (Endocardial Model)keywordten TusscherKHPenny NoblePanfilovAVAdded simulation metadata to allow simulation for 5 seconds.
Changed model cmeta:id to remove version number.NoblePenny2008-05-14T00:37:55+12:00Corrections to model name and stimulus current to enable running in COR.penny.noble@dpag.ox.ac.uk16565318Alternans and spiral breakup in a human ventricular tissue model.291108811002008-05-14T00:00:00+00:00American Journal of PhysiologyUniversity of Oxford10000.1100002008-06-19T11:14:49+12:00Penny NobleThe 2006 model is based on earlier ten Tusscher models, and incorporates recent experimental restitution data, an improved description of intracellular calcium dynamics - including subspace calcium dynamics which control L-type calcium current and calcium-induced calcium release (CICR,) by means of modelling CICR with a four-state Markov model for the ryanodine receptor - and incorporation of both fast and slow voltage-gated inactivation of the L-type calcium current.
This is the ENDOCARDIAL CELL VARIANT of the model. This model was created by Penny Noble of Oxford University and is known to read in COR and PCEnv.NoblePennyThe 2006 model is based on earlier ten Tusscher models, and incorporates recent experimental restitution data, an improved description of intracellular calcium dynamics - including subspace calcium dynamics which control L-type calcium current and calcium-induced calcium release (CICR,) by means of modelling CICR with a four-state Markov model for the ryanodine receptor - and incorporation of both fast and slow voltage-gated inactivation of the L-type calcium current.
This is the ENDOCARDIAL CELL VARIANT of the model. This model was created by Penny Noble of Oxford University and is known to read in COR and PCEnv.2006-09-00 00:00LawsonJamesRichardventricular myocytespiral breakupcardiac electrophysiologyelectrophysiologycardiacalternans