- 作者：Yaowalak Panyasing ; Anusak Kijtawornrat ; Carlos del Rio ; Cynthia Carnes ; Robert L. Hamlin
- 关键词：Hypertrophy ; Methods ; Rabbits ; Torsades de pointes
- 刊名：Journal of Pharmacological and Toxicological Methods
- 出版年：2010
- 出版时间：September-October 2010
- 年：2010
- 卷：62
- 期：2
- 页码：148-156
- 全文大小：974 K
IntroductionCardiac 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 8 weeks 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.