Fox, McHarg, Gilmour, 2002

Model Status

This model is known to run in PCEnv and COR to recreate the published results. The units have been checked and they are consistent.

Model Structure

The duration of a cardiac action potential is largely dependent on the length of the preceding diastolic interval. This relationship is called the action potential duration restitution relation, and if its slope is equal to or greater than 1, and alternation of action potential duration, or electrical alternans, often develops during high frequency pacing. Such rate-dependent electrical alternans may be a precursor to the development of ventricular arrhythmias, especially ventricular fibrillation. In support of this theory, several experiments have demonstrated that when the slope of the restitution relation is greater than 1, rapid pacing induces both alternans and fibrillation in isolated ventricles. However, to date, attempts to intervene with this process have been limited, and alternative, more effective, methods of suppressing alternans need to be identified.

To this end, mathematical models of the ventricular myocyte have been developed, with the ultimate aim of facilitating the discovery of new therapeutic targets. In the model described here in CellML, Jeffrey Fox et al. (2001) have developed a mathematical model of the canine ventricular myocyte. This model was, at least in part, based on the model published by Winslow et al. (1999) (also described in CellML), and it extends this model to reproduce sustained alternans at rapid pacing rates.

The complete original paper reference is cited below:

Ionic mechanism of electrical alternans, Jeffrey J. Fox, Jennifer L. McHarg, and Robert F. Gilmour Jr, 2001, American Journal of Physiology: Heart and Circulatory Physiology , 282, H516-H530. (Full text and PDF versions of the article are available to journal subscribers on the American Journal of Physiology: Heart and Circulatory Physiology website.) PubMed ID: 11788399

A schematic diagram describing the current flows across the cell membrane and the calcium fluxes between the cytoplasm and the sarcoplasmic reticulum that are captured in the Fox et al. canine ventricular cell model.