Arrhythmia Vulnerability in Diabetic Cardiac Tissue is Species-Dependent: Effects of I KATP, Uncoupling, and Connexin Lateralization

Abstract

Amongst the complications of diabetes is arrhythmia, the risk of which depends on multiple factors. This study was designed to investigate several factors, including the effects of ATP-sensitive potassium current, lateralized connexins, and gap junction uncoupling. ATP-sensitive potassium channel (IKATP) opening is caused by ischemia, which can occur in diabetic or non-diabetic hearts. IKATP opening was simulated in this work to determine if the risk of ischemia-induced arrhythmias is affected by diabetes. Simulations were performed using healthy and diabetic models of rat and rabbit ventricle. Results showed that the diabetic rat model is less vulnerable to reentrant arrhythmia than the healthy rat model. The diabetic rabbit model was more vulnerable to reentrant arrhythmia than the healthy rabbit model. In both rabbit models, the vulnerability increased as the gap junctional coupling decreased. Opening of IKATP resulted in larger window of vulnerability. Conduction reserve was simulated based on 1D simulations for both rat and rabbit models. There was no difference between rat and rabbit conduction reserve. Our results showed that the simulation results are model-dependent, i.e., results from the rabbit model are similar to human clinical data, while the results from the rat model contradict human clinical observations, suggesting a significant species-dependence in arrhythmia vulnerability in the diabetic heart.