Mathematical Modelling of Leptin-Induced Effects on Electrophysiological Properties of Rat Cardiomyocytes and Cardiac Arrhythmias

Abstract

Elevated plasma leptin levels, or hyperleptinemia, have been demonstrated to correlate with metabolic syndrome markers, including obesity, and may be an independent risk factor for the development of cardiovascular disease. In this paper, we use cardiac models to study possible effects of hyperleptinemia on the electrophysiological properties of cardiomyocytes and cardiac arrhythmias. We modified the parameters of an improved Gattoni 2016 model of rat ventricular cardiomyocytes to simulate experimental data for the leptin effects on ionic currents. We used four model variants to investigate the effects of leptin-induced parameter modification at the cellular level and in 2D tissue. In all models, leptin was found to increase the duration of the action potential. In some cases, we observed a dramatic change in the shape of the action potential from triangular, characteristic of rat cardiomyocytes, to a spike-and-dome, indicating predisposition to arrhythmias. In all 2D tissue models, leptin increased the period of cardiac arrhythmia caused by a spiral wave and enhanced dynamic instability, manifesting as increased meandering, onset of hypermeandering, and even spiral wave breakup. The leptin-modified cellular models developed can be used in subsequent research in rat heart anatomy models.