Effect of selective IK,ACh inhibition by XAF-1407 in an equine model of tachypacing-induced persistent atrial fibrillation

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: onr:"swepub:oai:lup.lub.lu.se:25565699-72d1-4acb-b46a-b5c51aa90a2c" > Effect of selective...

1 of 1
Previous record
Next record
To hitlist

Effect of selective IK,ACh inhibition by XAF-1407 in an equine model of tachypacing-induced persistent atrial fibrillation

Fenner, Merle Friederike (author): University of Copenhagen

Carstensen, Helena (author): University of Copenhagen

Dalgas Nissen, Sarah (author): University of Copenhagen

Melis Hesselkilde, Eva (author): University of Copenhagen

Scott Lunddahl, Christine (author): University of Copenhagen

Adler Hess Jensen, Maja (author): University of Copenhagen

Loft-Andersen, Ameli Victoria (author): University of Copenhagen

Sattler, Stefan Michael (author): University Hospital Munich,Ludwig-Maximilian University of Munich,Copenhagen University Hospital

Platonov, Pyotr (author): Lund University,Lunds universitet,Electrocardiology Research Group - CIEL,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital

El-Haou, Said (author): Xention Ltd

Jackson, Claire (author): Xention Ltd

Tang, Raymond (author): Xention Ltd

Kirby, Robert (author): Xention Ltd

Ford, John (author): Xention Ltd

Schotten, Ulrich (author): Maastricht University

Milnes, James (author): Xention Ltd

Svane Sørensen, Ulrik (author): Acesion Pharma

Jespersen, Thomas (author): University of Copenhagen

Buhl, Rikke (author): University of Copenhagen

show less...

(creator_code:org_t)

2020-06-24
2020
English 17 s.
In: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 177:16, s. 3778-3794

Related links:: http://dx.doi.org/10...; show more...; https://bpspubs.onli...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

Background and Purpose: Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF. Experimental Approach: The pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug-induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction. Key Results: XAF-1407 potently and selectively inhibited Kir3.1/3.4 and Kir3.4/3.4, underlying the IK,ACh current. XAF-1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (~20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened atrioventricular-nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia. Conclusion and Implications: XAF-1407 efficiently cardioverted sustained tachypacing-induced AF of short duration in horses without notable side effects. This supports IK,ACh inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Publication and Content Type

art (subject category)
ref (subject category)

Find in a library

British Journal of Pharmacology (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

Articles in the publication: British Journal ...

By the university: Lund University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se