Role of interventricular dispersion of repolarization in acquired torsade-de-pointes arrhythmias: reversal by magnesium.
OBJECTIVE
The mechanism of acquired torsade-de-pointes arrhythmias (TdP) is not clear but is suggested to be based on several parameters including early afterdepolarizations (EADs) and/or dispersion of repolarization (delta APD). In our animal model of TdP (anaesthetized dogs with chronic AV block), we assessed the relevance of interventricular dispersion for the initiation of TdP.


METHODS
In 24 experiments, multiple endocardial monophasic action potential (MAP) recordings were made at baseline, after d-sotalol (2 mg/kg), and after MgSO4 (100 mg/kg, n = 11) to measure regional differences in action potential duration (APD). Rate-dependent behavior of the interventricular delta APD (APD of left minus right ventricle) and intraventricular dispersion was studied under the different circumstances.


RESULTS
Dogs with induction of TdP by d-sotalol and pacing (11/20 = 55%) had longer cycle lengths of idioventricular rhythm, longer QT-durations, increased presence of EADs (14/22 vs 5/18 MAPs, P < 0.05) and increased interventricular delta APD (135 +/- 55 vs 60 +/- 40 ms. P < 0.05) compared with non-inducible dogs. There were no differences in intraventricular dispersion. MgSO4 diminished delta APD (110 +/- 45 to 55 +/- 60 ms, P < 0.05) and prevented TdP (4/4). In contrast to intraventricular dispersion, interventricular delta APD is clearly bradycardia-dependent.


CONCLUSIONS
Next to bradycardia, prolonged repolarization, and EADs, we propose that delta APD should be added to the relevant factors for the initiation of TdP. Interventricular dispersion is much larger than intraventricular dispersion and demonstrates a very strong bradycardia dependence.
Verduyn
S C
SC
Department of Cardiology, Cardiovascular Research Institute Maastricht, University of Limburg, Netherlands.
Vos
M A
MA
van der Zande
J
J
van der Hulst
F F
FF
Wellens
H J
HJ
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000503:physiopathology*; D008278:Magnesium Sulfate / Q000627:therapeutic use*; D008297:Male; D013015:Sotalol; D016171:Torsades de Pointes / Q000188:drug therapy / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D008278:Magnesium Sulfate; D013015:Sotalol