The K
KCa2
SK channels
antiarrhythmic drugs
atrial fibrillation
ion channels
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2020
2020
Historique:
received:
16
12
2019
accepted:
07
02
2020
entrez:
18
3
2020
pubmed:
18
3
2020
medline:
18
3
2020
Statut:
epublish
Résumé
To describe the effects of the K Six healthy pigs with implanted pacemakers and equipped with a Holter monitor were used to compare the effects of increasing doses (0, 5, 10, 15, 20, and 25 mg/kg) of AP30663 on the right atrial effective refractory period (AERP) and on various ECG parameters, including the QT interval. Ten pigs with implanted neurostimulators were long-term atrially tachypaced (A-TP) until sustained vernakalant-resistant AF was present. 20 mg/kg AP30663 was tested to discover if it could successfully convert vernakalant-resistant AF to sinus rhythm (SR) and protect against reinduction of AF. Seven anesthetized pigs were used for pharmacokinetic experiments. Two pigs received an infusion of 20 mg/kg AP30663 over 60 min while five pigs received 5 mg/kg AP30663 over 30 min. Blood samples were collected before, during, and after infusion on AP30663. AP30663 was well-tolerated and prominently increased the AERP in pigs with little effect on ventricular repolarization. Furthermore, it converted A-TP induced AF that had become unresponsive to vernakalant, and it prevented reinduction of AF in pigs. Both a >30 ms increase of the AERP and conversion of AF occurred in different pigs at a free plasma concentration level of around 1.0-1.4 µM of AP30663, which was achieved at a dose level of 5 mg/kg. AP30663 has shown properties in animals that would be of clinical interest in man.
Identifiants
pubmed: 32180722
doi: 10.3389/fphar.2020.00159
pmc: PMC7059611
doi:
Types de publication
Journal Article
Langues
eng
Pagination
159Informations de copyright
Copyright © 2020 Diness, Kirchhoff, Speerschneider, Abildgaard, Edvardsson, Sørensen, Grunnet and Bentzen.
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