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

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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 (I KATP) opening is caused by ischemia, which can occur in diabetic or non-diabetic hearts. I KATP 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 I KATP 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.

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Acknowledgments

This research was supported by Natural Sciences and Engineering Research Council of Canada (NSERC). Funding was provided by Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada.

Conflict of interest

To the best of our knowledge, no conflict of interest, financial or other, exists.

Statement of human and animal studies

The study did not include human or animal experiments.

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Authors and Affiliations

  1. Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB, Canada

    A. Ghazanfari

  2. Department of Electrical and Computer Engineering, and LIRYC, University of Bordeaux 1, Talence, France

    E. Vigmond

  3. Department of Electrical and Computer Engineering, and Centre for Bioengineering Research & Education, Schulich School of Engineering, University of Calgary, Calgary, AB, Canada

    A. Nygren

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Correspondence to A. Ghazanfari.

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Associate Editors Robert L. Abraham and Ajit P. Yoganathan oversaw the review of this article.

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Ghazanfari, A., Vigmond, E. & Nygren, A. Arrhythmia Vulnerability in Diabetic Cardiac Tissue is Species-Dependent: Effects of I KATP, Uncoupling, and Connexin Lateralization. Cardiovasc Eng Tech 8, 527–538 (2017). https://doi.org/10.1007/s13239-017-0315-0

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