ArticleCardiovascular research2021
Two-hit mechanism of cardiac arrhythmias in diabetic hyperglycaemia: reduced repolarization reserve, neurohormonal stimulation, and heart failure exacerbate susceptibility.
Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes.Clinical research in cardiology : official journal of the German Cardiac Society · 2022Trial
- Clinical trials in a dish: cardiometabolic drug development with biological and digital twins.The Journal of clinical investigation · 2026Review
- Empagliflozin restores cardiac function in obese-diabetic HFpEF mice but further alters gene expression.Basic research in cardiology · 2026Article
- Hyperglycaemia-induced reactive oxygen species production in cardiac ventricular myocytes differs among mammals.The Journal of physiology · 2026Article
- Targeting Arrhythmogenic Late Sodium Current by FHF1Circulation research · 2026Article
- Dynamic visualization of physiological CaMKII activity using sensitive FRET biosensors.bioRxiv : the preprint server for biology · 2026Article
- Association of glycemic variability with the risk of new-onset atrial fibrillation and death in critically ill patients without diabetes: analysis of the MIMIC-IV database.Diabetology & metabolic syndrome · 2026Article
- Prognostic value of glycaemic variability for mortality in cardiogenic shock patients: a retrospective cohort study.Cardiovascular diabetology · 2025Article
- Calcium Signaling and Cardiac Adaptation to Stress: Focus on Pregnancy and Diabetes.Biomolecules · 2025Review
- Spotlight on mechanism of sudden unexpected death in epilepsy in Dravet syndrome.Translational psychiatry · 2025Review
- Impact of hybrid closed-loop insulin delivery on cardiac rhythm in older adults with type 1 diabetes: A post hoc analysis of trial data.Diabetes, obesity & metabolism · 2024Article
- SparkMaster 2: A New Software for Automatic Analysis of Calcium Spark Data.Circulation research · 2023Article
- Review
- Glycemic variability and in-hospital death of critically ill patients and the role of ventricular arrhythmias.Cardiovascular diabetology · 2023Article
- Distinct Cardiac Connexin-43 Expression in Hypertrophied and Atrophied Myocardium May Impact the Vulnerability of the Heart to Malignant Arrhythmias. A Pilot Study.Physiological research · 2023Article
- Association of hyperglycemia ratio and ventricular arrhythmia in critically ill patients admitted to the intensive care unit.BMC cardiovascular disorders · 2023Observational
- Diabetes and Excess Aldosterone Promote Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2022Article
- Does Myocardial Atrophy Represent Anti-Arrhythmic Phenotype?Biomedicines · 2022Review
- Protein Kinase D1 Regulates Cardiac Hypertrophy, Potassium Channel Remodeling, and Arrhythmias in Heart Failure.Journal of the American Heart Association · 2022Article
- Celebrities in the heart, strangers in the pancreatic beta cell: Voltage-gated potassium channels KActa physiologica (Oxford, England) · 2022Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
aimsDiabetic hyperglycaemia is associated with increased arrhythmia risk. We aimed to investigate whether hyperglycaemia alone can be accountable for arrhythmias or whether it requires the presence of additional pathological factors. METHODS AND
resultsAction potentials (APs) and arrhythmogenic spontaneous diastolic activities were measured in isolated murine ventricular, rabbit atrial, and ventricular myocytes acutely exposed to high glucose. Acute hyperglycaemia increased the short-term variability (STV) of action potential duration (APD), enhanced delayed afterdepolarizations, and the inducibility of APD alternans during tachypacing in both murine and rabbit atrial and ventricular myocytes. Hyperglycaemia also prolonged APD in mice and rabbit atrial cells but not in rabbit ventricular myocytes. However, rabbit ventricular APD was more strongly depressed by block of late Na+ current (INaL) during hyperglycaemia, consistent with elevated INaL in hyperglycaemia. All the above proarrhythmic glucose effects were Ca2+-dependent and abolished by CaMKII inhibition. Importantly, when the repolarization reserve was reduced by pharmacological inhibition of K+ channels (either Ito, IKr, IKs, or IK1) or hypokalaemia, acute hyperglycaemia further prolonged APD and further increased STV and alternans in rabbit ventricular myocytes. Likewise, when rabbit ventricular myocytes were pretreated with isoproterenol or angiotensin II, hyperglycaemia significantly prolonged APD, increased STV and promoted alternans. Moreover, acute hyperglycaemia markedly prolonged APD and further enhanced STV in failing rabbit ventricular myocytes.
conclusionWe conclude that even though hyperglycaemia alone can enhance cellular proarrhythmic mechanisms, a second hit which reduces the repolarization reserve or stimulates G protein-coupled receptor signalling greatly exacerbates cardiac arrhythmogenesis in diabetic hyperglycaemia.
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