The new selective I(Ks)-blocking agent HMR 1556 restores sinus rhythm and prevents heart failure in pigs with persistent atrial fibrillation

Basic Research in Cardiology
Alexander BauerWolfgang Schoels

Abstract

Antiarrhythmic drugs for treatment of atrial fibrillation in patients with heart failure are limited by proarrhythmia and low efficacy. Experimental studies indicate that the pure I(Ks) blocking agents chromanol 293b and HMR 1556 prolong repolarization more markedly at fast than at slow heart rates and during beta-adrenergic stimulation. These properties may overcome some of the above quoted limitations. Ten domestic swine underwent pacemaker implantation (PM) and atrial burst pacing to induce persistent AF. Four days after onset of persistent AF, pigs were randomized to HMR 1556 (30 mg/kg, p.o., 10 days) or placebo. All animals receiving HMR 1556 converted to SR (5.2 +/- 1.9 days), whereas placebo pigs remained in AF. Pigs treated with placebo developed high ventricular rates (297 +/- 5 bpm) and severe heart failure, whereas pigs treated with HMR 1556 remained hemodynamically stable. Left ventricular ejection fraction on the day of euthanization was significantly lower in the placebo compared to the HMR 1556 group (30 +/- 4% vs. 69 +/- 5%, p < 0.005). Similar results were seen with epinephrine levels (placebo 1563 +/- 193 pmol/l vs. HMR 613 +/-196 pmol/l, p < 0.05). Right atrial monophasic action potentials were significantly ...Continue Reading

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Citations

Dec 2, 2009·Nature Reviews. Drug Discovery·Heike WulffLuis A Pardo
Feb 22, 2011·Pharmacology & Therapeutics·A J WorkmanA C Rankin
Apr 19, 2007·Physics in Medicine and Biology·Janine BeckerNina Petoussi-Henss
Mar 22, 2019·Nature Reviews. Cardiology·Sebastian ClaussStefan Kääb
May 29, 2021·RSC Medicinal Chemistry·Matteo BorginiPeter Wipf

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