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Original Articles

Fever Accentuates Transmural Dispersion of Repolarization and Facilitates Development of Early Afterdepolarizations and Torsade de Pointes Under Long-QT Conditions

Alexander Burashnikov, PhD; Wataru Shimizu, MD, PhD and Charles Antzelevitch, PhD

From the Masonic Medical Research Laboratory, Utica, NY (A.B., C.A.), and the Division of Cardiology, Department of Internal Medicine, National Cardiovascular Center, Osaka, Japan (W.S.).

Correspondence to Dr Alexander Burashnikov, Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, New York 13501. E-mail sasha{at}mmrl.edu

Received January 22, 2007; accepted May 30, 2008.

Background— The arrhythmogenic effects of hyperthermia have been highlighted in the Brugada syndrome but remain largely unexplored in other arrhythmic syndromes. The present study examines the effect of hyperthermia on transmural dispersion of action potential duration (TD-APD), early afterdepolarization (EAD) activity, and torsade de pointes (TdP) under long-QT conditions.

Methods and Results— Standard and floating glass microelectrodes were used to record action potentials from epicardial, M cell, and endocardial regions of the arterially perfused left ventricle wedge, from tissue slices isolated from these regions, and from isolated Purkinje fibers. A transmural ECG was simultaneously recorded across the wedge. Under baseline conditions and in the presence of I_Ks block (chromanol 293B), hyperthermia (39°C to 40°C) abbreviated APD in tissue slices from all 3 regions. In the presence of I_Kr block (E-4031), hyperthermia prolonged APD and induced or augmented EADs in M cell and Purkinje preparations at pacing cycle lengths 800 ms but abbreviated APD in epicardium and endocardium, resulting in a marked accentuation of TD-APD. Ryanodine prevented the hyperthermia-induced EAD. In perfused wedge preparations, hyperthermia abbreviated APD throughout both in the absence or presence of I_Kr or I_Ks block and did not induce EADs or TdP. Combined I_Kr and I_Ks block increased TD-APD and induced EADs (4/12) and spontaneous TdP (3/12) at 36°C to 37°C; hyperthermia (39°C to 40°C) further accentuated TD-APD and facilitated the development of EAD activity (9/12) and TdP (6/12).

Conclusions— Our findings suggest that hyperthermia can be associated with an increased arrhythmic risk when the repolarization reserve of the myocardium is compromised.

Key Words: arrhythmias • electrophysiology • fever • long-QT syndrome • triggered activity

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Fever Accentuates Transmural Dispersion of Repolarization and Facilitates Development of Early Afterdepolarizations and Torsade de Pointes Under Long-QT Conditions

Alexander Burashnikov, Wataru Shimizu, and Charles Antzelevitch
Circ Arrhythmia Electrophysiol 2008 1: 202-208. [Abstract] [Full Text] [PDF]