Proarrhythmic Effect of Acetylcholine-Esterase Inhibitors Used in the Treatment of Alzheimer's Disease: Benefit of Rivastigmine in an Experimental Whole-Heart Model.

Proarrhythmic Effect of Acetylcholine-Esterase Inhibitors Used in the Treatment of Alzheimer's Disease: Benefit of Rivastigmine in an Experimental Whole-Heart Model. Cardiovasc Toxicol. 2019 Jul 13;: Authors: Ellermann C, Coenen A, Niehues P, Leitz P, Kochhäuser S, Dechering DG, Fehr M, Eckardt L, Frommeyer G Abstract Several studies suggest QT prolongation and torsade de pointes with acetylcholine-esterase inhibitors. We therefore examined the electrophysiologic profile of donepezil, rivastigmine, and galantamine in a sensitive whole-heart model of proarrhythmia. 34 rabbit hearts were isolated and retrogradely perfused employing the Langendorff setup. Hearts were treated either with donepezil, rivastigmine, or galantamine in rising concentrations and electrophysiologic studies were performed. In the presence of donepezil and galantamine, spatial dispersion of repolarization was amplified. Cardiac repolarization (QT interval and action potential duration) was prolonged with donepezil but not with galantamine. Remarkably, both drugs induced triggered activity (early afterdepolarizations and torsade de pointes tachycardia). Despite a pronounced prolongation of repolarization with rivastigmine, no increase in spatial dispersion of repolarization and thus no triggered activity was observed. In the present study, donepezil and galantamine provoked triggered activity, whereas rivastigmine did not have proarrhythmic effects. Spatial disper...
Source: Cardiovascular Toxicology - Category: Cardiology Authors: Tags: Cardiovasc Toxicol Source Type: research