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Pharmacol Ther. 2008 Aug;119(2):168-78. doi: 10.1016/j.pharmthera.2008.03.006. Epub 2008 Apr 6.

The canine model with chronic, complete atrio-ventricular block.

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  • 1Department of Medical Physiology, Division Heart and Lungs, UMC Utrecht, Yalelaan 50, 3584 CM Utrecht, The Netherlands.

Abstract

Proarrhythmic susceptibility to drug-induced Torsades de Pointes is restricted to individuals with a predisposed phenotype characterized by a reduced repolarization reserve. Additional factors are often involved in a further impairment of repolarization, possibly culminating with dangerous ventricular polymorphic tachyarrhythmias. Drugs that block repolarizing currents represent such an additional hit. The dog model with chronic, complete atrio-ventricular block has been used frequently for proarrhythmic drug screening. The ventricular remodeling seen after ablation of the AV node enhances the susceptibility for repolarization-dependent arrhythmias. In this review, we 1) describe the cellular and molecular basis of ventricular remodeling, 2) validate the CAVB dog as a drug screening model and 3) introduce a new surrogate predictive proarrhythmic parameter: beat-to-beat variability of repolarization.

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