Fever accentuates transmural dispersion of repolarization and facilitates development of early afterdepolarizations and torsade de pointes under long-QT Conditions.
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.


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 degrees C to 40 degrees 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 > or = 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 degrees C to 37 degrees C; hyperthermia (39 degrees C to 40 degrees 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.
Burashnikov
Alexander
A
Masonic Medical Research Laboratory, Utica, NY 13501, USA. sasha@mmrl.edu
Shimizu
Wataru
W
Antzelevitch
Charles
C
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D005334:Fever / Q000150:complications* / Q000503:physiopathology; D006979:Hyperthermia, Induced / Q000009:adverse effects; D008133:Long QT Syndrome / Q000150:complications* / Q000503:physiopathology; D011690:Purkinje Fibers / Q000503:physiopathology*; D016171:Torsades de Pointes / Q000209:etiology* / Q000503:physiopathology