Anti‐fibrillatory effects of F17727, a new IKur blocker, in rats and rabbits with myocardial infarction or heart failure (652.17)

Autor: Christophe Pignier, Didier Junquero, Yvan Verscheure, Stéphane N. Hatem, Alain Latil, Robert Létienne, Nathalie Mougenot, Bruno Le Grand
Rok vydání: 2014
Předmět:
Zdroj: The FASEB Journal. 28
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fasebj.28.1_supplement.652.17
Popis: Atrial fibrillation (AF) can be triggered by myocardial infarction (MI) or heart failure (HF). The blockade of the ultra-rapid outward rectifier potassium current IKur is an attractive goal to control the repolarization of cardiac atria. F17727 was evaluated in patch-clamp assays, in rat post-MI and in HF in rabbit and dog. F17727 blocked human IKur (IC50=1.8µM) and did not impact IKr, IKs, INa. In rats 2 months after coronary artery ligation, the left atria surface increased by 50-150%; transœsophagial electrical bursts induced AF which lasted 5-21s in vehicle-MI rats but lower than 5s in sham. An acute iv treatment by F17727 (2.5 and 5mg/kg) significantly reduced AF induction at the level of sham. In rabbits, 2-week left atria tachypacing up to 1200bpm triggered electrical and structural remodeling; electrical stimuli induced AF. An acute iv treatment by F17727 (racemate, 2.5mg/kg) reduced AF (mean spontaneous and induced AF duration of 4±4s and 82±49s) when compared to vehicle (165±75s and 261±45s resp...
Databáze: OpenAIRE
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