Schneider, H. -J. and Husser, O. and Rihm, M. and Fredersdorf, S. and Birner, C. and Dhein, S. and Muders, F. and Jeron, A. and Goegelein, H. and Riegger, G. A. and Luchner, Andreas (2009) Safety of the novel atrial-selective K+-channel blocker AVE0118 in experimental heart failure. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 379 (3). pp. 225-232. ISSN 0028-1298, 1432-1912
Full text not available from this repository. (Request a copy)Abstract
Congestive heart failure (CHF) is often associated with atrial fibrillation. The safety of many antiarrhythmic drugs in CHF is limited by proarrhythmic effects. We aimed to assess the safety of a novel atrial-selective K+-channel blocker AVE0118 in CHF compared to a selective (dofetilide) and a non-selective IKr blocker (terfenadine). For the induction of CHF, rabbits (n = 12) underwent rapid right ventricular pacing (330-380 bpm for 30 days). AVE0118 (1 mg/kg) dofetilide (0.02 mg/kg) and terfenadine (2 mg/kg) were administered in baseline (BL) and CHF. A six-lead ECG was continuously recorded digitally for 30 min after each drug administration. At BL, dofetilide and terfenadine significantly prolonged QTc interval (218 +/- 30 ms vs 155 +/- 8 ms, p = 0.001 and 178 +/- 23 ms vs. 153 +/- 12 ms, p = 0.01, respectively) while QTc intervals were constant after administration of AVE0118 (p = n.s.). In CHF, dofetilide and terfenadine caused torsades de pointes and symptomatic bradycardia, respectively, and prolonged QTc interval (178 +/- 30 ms vs. 153 +/- 14 ms, p = 0.02 and 157 +/- 7 ms vs. 147 +/- 10 ms, p = 0.02, respectively) even at reduced dosages, whereas no QTc-prolongation or arrhythmia was observed after full-dose administration of AVE0118. In conclusion, atrial-selective K+-channel blockade by AVE0118 appears safe in experimental CHF.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VENTRICULAR EJECTION FRACTIONS; CARDIAC ION CHANNELS; TORSADES-DE-POINTES; ANTIHISTAMINE TERFENADINE; DRUG AVE0118; I-KUR; FIBRILLATION; DOFETILIDE; ENALAPRIL; MYOCYTES; Congestive heart failure; AVE0118; Antiarrhythmic drugs; Atrial fibrillation; Torsades de pointes; QT prolongation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Oct 2020 06:52 |
| Last Modified: | 05 Oct 2020 06:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29425 |
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