Published Online
on May 30, 2008

A more recent version of this article appeared on August 1, 2008

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Original Article

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

Alexander Burashnikov^1,3, Wataru Shimizu² and Charles Antzelevitch¹

¹ Masonic Medical Research Laboratory;
² National Cardiovascular Center

Correspondence: ³ E-mail: sasha{at}mmrl.edu

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 LV wedge, from tissue slices isolated from these regions, as well as 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 (39-40°C) abbreviated APD in tissue slices from all three 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 36-37°C; hyperthermia (39-40°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: action potentials • arrhythmia • electrophysiology • long-QT syndrome • Fever

Related Article

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]