Stretch-induced changes in arrhythmogenesis and excitability in experimentally based heart cell models

Stretch-induced changes in arrhythmogenesis and excitability in experimentally based heart cell models

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

Cardiac mechanoelectric coupling (that is, the influence of mechanical activity on the electrical state of the heart) has been well documented. It has been suggested that hearts that have been mechanically compromised by congestive heart failure display an increased prevalence of arrhythmia. In addition, in vitro studies have shown that sudden cardiac tissue stretch can stimulate arrhythmias. One hypothesised mechanism for the stretch sensitivity of cardiac muscle is the presence of stretch-activated channels (SACs).

In their 1998 study, Riemer et al. investigate the potential role of SACs in excitability and arrhythmogenesis. To do this they added a linear, time-independent, stretch-sensitive current to the Luo-Rudy membrane model for guinea pig ventricular myocytes (see Luo-Rudy I model and Zeng et al. 1995 model for more details, and also see the figure below). Model simulations showed that increased stretch conductance led to resting potential depolarisation, a decreased excitation threshold, altered action potential duration, and, under certain conditions, early afterdepolarisations. From these results Riemer et al. concluded that stretch increases cellular excitability, making the heart prone to ectopic activity. Regional effects of stretch on action potential are influenced by factors such as the SAC reversal potential, ionic conditions and baseline refractoriness throughout the heart and therefore an increased risk of arrhythmia.

The complete original paper reference is cited below:

Stretch-induced changes in arrhythmogenesis and excitability in experimentally based heart cell models, Tara L. Riemer, Eric A. Sobie, and Leslie Tung, 1998, American Journal of Physiology , 275, H431-H442. (Full text and PDF versions of the article are available for journal members on the American Journal of Physiology website.) PubMed ID: 9683430

A schematic diagram describing the ionic components of the Riemer et al. 1998 mathematical model of a guinea pig ventricular myocyte. The model is based on the Luo-Rudy dynamic model, with an added stretch-activated channel (SAC).