Hypoglycaemia combined with mild hypokalaemia reduces the heart rate and causes abnormal pacemaker activity in a computational model of a human sinoatrial cell.
Hypoglycaemia combined with mild hypokalaemia reduces the heart rate and causes abnormal pacemaker activity in a computational model of a human sinoatrial cell.
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DOI：
10.1098/rsif.2021.0612
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Clayton RH
中科院分区：
文献类型：
--
作者：
Bernjak A;Iqbal A;Heller SR;Clayton RH
低血糖，低血糖，被认为是糖尿病患者心源性猝死（SCD）的可能因素，但在临床研究中进行调查具有挑战性。我们假设低血糖对心脏窦房结 (SAN) 的影响是一种候选机制，并采用 Fabbri 等人开发的人类 SAN 动作电位计算模型来研究低血糖对起搏器频率的影响。使用拉丁超立方采样，我们将低葡萄糖（LG）对人体ether-a-go-go相关基因通道的影响与血钾降低、低钾血症以及增加交感神经和副交感神经刺激结合起来。我们发现，低血糖本身会导致心率小幅下降，但与低钾血症合并时，心率也会明显下降。与正常血糖相比，低钾血症和低钾血症的交感神经刺激作用减弱，导致心率增加幅度较小。相比之下，副交感神经刺激的效果增强，导致心率更大程度下降。因此，我们证明了低血糖引起的心动过缓的潜在机制解释，并表明窦性停搏是糖尿病患者发生 SCD 的一种可能机制。
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.
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DOI：
10.1046/j.1365-2362.2003.01123.x
发表时间：
2003-02-01
影响因子：
5.5
作者：
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影响因子：
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影响因子：
158.5
作者：
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影响因子：
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