A tale of two dogs: analyzing two models of canine ventricular electrophysiology

The extensive development of detailed mathematical models of cardiac myocyte electrophysiology in recent years has led to a proliferation of models, including many that model the same animal species and specific region of the heart and thus would be expected to have similar properties. In this paper we review and compare two recently developed mathematical models of the electrophysiology of canine ventricular myocytes. To clarify their similarities and differences, we also present studies using them in a range of preparations from single cells to two-dimensional tissue. The models are compared with each other and with new and previously published experimental results in terms of a number of their properties, including action potential morphologies; transmembrane currents during normal heart rates and during alternans; alternans onsets, magnitudes, and cessations; and reentry dynamics of spiral waves. Action potential applets and spiral wave movies for the two canine ventricular models are available online as supplemental material. We find a number of differences between the models, including their rate dependence, alternans dynamics, and reentry stability, and a number of differences compared with experiments. Differences between models of the same species and region of the heart are not unique to these canine models. Similar differences can be found in the behavior of two models of human ventricular myocytes and of human atrial myocytes. We provide several possible explanations for the differences observed in models of the same species and region of the heart and discuss the implications for the applicability of models in addressing questions of mechanism in cardiac electrophysiology.