Open AccessHypoglycaemia combined with mild hypokalaemia reduces the heart rate and causes abnormal pacemaker activity in a computational model of a human sinoatrial cell
Author(s) -
Alan Bernjak,
Ahmed Iqbal,
Simon Heller,
Richard H. Clayton
Publication year - 2021
Publication title -
journal of the royal society interface
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 139
eISSN - 1742-5689
pISSN - 1742-5662
DOI - 10.1098/rsif.2021.0612
Subject(s) - heart rate , medicine , bradycardia , stimulus (psychology) , cardiology , sinoatrial node , sick sinus syndrome , endocrinology , diabetes mellitus , hypoglycemia , insulin , blood pressure , psychology , psychotherapist
Low blood glucose, hypoglycaemia, has been implicated as a possible contributing factor to sudden cardiac death (SCD) in people with diabetes but it is challenging to investigate in clinical studies. We hypothesized the effects of hypoglycaemia on the sinoatrial node (SAN) in the heart to be a candidate mechanism and adapted a computational model of the human SAN action potential developed by Fabbri et al. , to investigate the effects of hypoglycaemia on the pacemaker rate. Using Latin hypercube sampling, we combined the effects of low glucose (LG) on the human ether-a-go-go-related gene channel with reduced blood potassium, hypokalaemia, and added sympathetic and parasympathetic stimulus. We showed that hypoglycaemia on its own causes a small decrease in heart rate but there was also a marked decrease in heart rate when combined with hypokalaemia. The effect of the sympathetic stimulus was diminished, causing a smaller increase in heart rate, with LG and hypokalaemia compared to normoglycaemia. By contrast, the effect of the parasympathetic stimulus was enhanced, causing a greater decrease in heart rate. We therefore demonstrate a potential mechanistic explanation for hypoglycaemia-induced bradycardia and show that sinus arrest is a plausible mechanism for SCD in people with diabetes.