Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models

Frontiers in Cardiovascular Medicine

Shuk Han Cheng¹  Aishwarya Bhardwaj²  Abhishek C. Sawant²  Kamalan Jeevaratnam³  Ka Hou Christien Li⁴  Gan-Xin Yan⁵  Chloe Kwong Yee Cheung⁶  Wing Tak Wong⁷  Henggui Zhang⁸  Konstantinos P. Letsas⁹  Nazish Sayed^1,10  Tong Liu^1,11  Gary Tse^1,12 

[1] Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong, China;State Key Laboratory of Marine Pollution (SKLMP), City University of Hong Kong, Hong Kong, China;Department of Materials Science and Engineering, College of Science and Engineering, City University of Hong Kong, Hong Kong, China;Division of Cardiology, Department of Internal Medicine, State University of New York at Buffalo, Buffalo, NY, United States;Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom;Faculty of Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom;Lankenau Institute for Medical Research and Lankenau Medical Center, Wynnewood, PA, United States;Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;School of Life Sciences, Chinese University of Hong Kong, Hong Kong, China;School of Physics and Astronomy, The University of Manchester, Manchester, United Kingdom;Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Athens, Greece;Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States;Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, United States;Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA, United States;Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China;Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China;Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom;

关键词: hypokalaemia;    potassium;    cardiac arrhythmia;    conduction;    repolarization;   

DOI  :  10.3389/fcvm.2021.620539

来源: Frontiers

【 摘 要 】

Potassium is the predominant intracellular cation, with its extracellular concentrations maintained between 3. 5 and 5 mM. Among the different potassium disorders, hypokalaemia is a common clinical condition that increases the risk of life-threatening ventricular arrhythmias. This review aims to consolidate pre-clinical findings on the electrophysiological mechanisms underlying hypokalaemia-induced arrhythmogenicity. Both triggers and substrates are required for the induction and maintenance of ventricular arrhythmias. Triggered activity can arise from either early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs). Action potential duration (APD) prolongation can predispose to EADs, whereas intracellular Ca2+ overload can cause both EADs and DADs. Substrates on the other hand can either be static or dynamic. Static substrates include action potential triangulation, non-uniform APD prolongation, abnormal transmural repolarization gradients, reduced conduction velocity (CV), shortened effective refractory period (ERP), reduced excitation wavelength (CV × ERP) and increased critical intervals for re-excitation (APD–ERP). In contrast, dynamic substrates comprise increased amplitude of APD alternans, steeper APD restitution gradients, transient reversal of transmural repolarization gradients and impaired depolarization-repolarization coupling. The following review article will summarize the molecular mechanisms that generate these electrophysiological abnormalities and subsequent arrhythmogenesis.

【 授权许可】

CC BY