Uni- or bi-ventricular hypertrophy and susceptibility to drug-induced torsades de pointes.
BACKGROUND
Cardiac hypertrophy is an independent risk factor for torsades de pointes (TdP), a polymorphic ventricular tachycardia that is often drug-induced, that may evolve into ventricular fibrillation and sudden death. Therefore this study was designed to determine if right (RVH), left (LVH), or biventricular (BVH) hypertrophy increases susceptibility to drug-induced TdP.


METHODS
Rabbits were separated into 4 groups: control or RVH, LVH, BVH (studied 8weeks after banding of one or both great arteries). ECGs were recorded continuously under anesthesia after baseline and after rabbits received escalating doses of torsadogens (dofetilide, clofilium and terfenadine) or non-torsadogens (cilobradine, diltiazem and vehicle). The following parameters were measured [RR, PQ, QRS and QT] or calculated [QTc (F), short term variability of QT interval].


RESULTS
Generally, torsadogenicity for the compounds tested was dofetilide>clofilium>terfenadine, and there was no TdP following cilobradine, diltiazem or vehicle. In general the susceptibility to TdP was RVH>BVH>LVH>control. Rabbits with RVH developed TdP much more prevalently than for those with either LVH or BVH (p<0.05). At the low dose of dofetilide, LVH was actually protective.


CONCLUSIONS
Rabbits with any form of hypertrophy develop prolongation of QT, QTc and increased QT instability. Rabbits with any form of hypertrophy are more prone to arrhythmia than normals in response to known torsadogens.
Panyasing
Yaowalak
Y
Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.
Kijtawornrat
Anusak
A
Del Rio
Carlos
C
Carnes
Cynthia
C
Hamlin
Robert L
RL
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000494:pharmacology; D016757:Death, Sudden, Cardiac / Q000662:veterinary; D004198:Disease Susceptibility / Q000662:veterinary; D004562:Electrocardiography / Q000187:drug effects / Q000662:veterinary; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000662:veterinary*; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology / Q000662:veterinary; D011817:Rabbits; D013686:Telemetry / Q000662:veterinary; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000662:veterinary; D020257:Ventricular Remodeling / Q000187:drug effects
D000889:Anti-Arrhythmia Agents