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J Pharmacol Toxicol Methods. 2010 Sep-Oct;62(2):148-56. doi: 10.1016/j.vascn.2010.04.007. Epub 2010 May 8.

Uni- or bi-ventricular hypertrophy and susceptibility to drug-induced torsades de pointes.

Author information

1
Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.

Abstract

INTRODUCTION:

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.

CONCLUSION:

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.

PMID:
20435152
DOI:
10.1016/j.vascn.2010.04.007
[Indexed for MEDLINE]

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