Published online before print March 28, 2002, doi: 10.1161/01.RES.0000016960.61087.86
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© 2002 American Heart Association, Inc.
Cellular Biology |
Ionic Current Basis of Electrocardiographic Waveforms
A Model Study
From the Cardiac Bioelectricity Research and Training Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
Correspondence to Dr Yoram Rudy, Director, Cardiac Bioelectricity Research and Training Center, 509 Wickenden Bldg, Case Western Reserve University, Cleveland, OH 44106-7207. E-mail yxr{at}po.cwru.edu
Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiographic waveforms to cellular electrophysiological processes. This modeling study establishes the following principles: (1) voltage gradients created by heterogeneities of the slow-delayed rectifier (IKs) and transient outward (Ito) potassium current inscribe the T wave and J wave, respectively; T-wave polarity and width are strongly influenced by the degree of intercellular coupling through gap-junctions. (2) Changes in [K+]o modulate the T wave through their effect on the rapid-delayed rectifier, IKr. (3) Alterations of IKs, IKr, and INa (fast sodium current) in long-QT syndrome (LQT1, LQT2, and LQT3, respectively) are reflected in characteristic QT-interval and T-wave changes; LQT1 prolongs QT without widening the T wave. (4) Accelerated inactivation of INa on the background of large epicardial Ito results in ST elevation (Brugada phenotype) that reflects the degree of severity. (5) Activation of the ATP-sensitive potassium current, IK(ATP), is sufficient to cause ST elevation during acute ischemia. These principles provide a mechanistic cellular basis for interpretation of electrocardiographic waveforms.
Key Words: electrocardiography • mathematical modeling • long-QT syndrome • Brugada syndrome • ischemia
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