Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction
| Autor: | Marion Kuiper, Jonas Goldin Diness, Vladimír Sobota, Carlotta Citerni, Ulrich Schotten, Bo Hjorth Bentzen, Sander Verheule, Stef Zeemering, Thomas Jespersen, Ulrik Svane Sørensen, Arne van Hunnik, Giulia Gatta |
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| Přispěvatelé: | RS: Carim - H08 Experimental atrial fibrillation, Fysiologie, RS: Carim - Heart |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Atrial mapping medicine.medical_treatment SK channel inhibition 030204 cardiovascular system & hematology Cardioversion Nerve conduction velocity SK channel 03 medical and health sciences 0302 clinical medicine Basic Science TACHYARRHYTHMIAS Physiology (medical) Internal medicine medicine Humans AcademicSubjects/MED00200 Heart Atria Cycle length 030304 developmental biology Fibrillation 0303 health sciences Fibrillatory conduction AP14145 business.industry Effective refractory period Atrial fibrillation medicine.disease ACTIVATED POTASSIUM CHANNEL Cardiology medicine.symptom Cardiology and Cardiovascular Medicine business Anti-Arrhythmia Agents |
| Zdroj: | EP Europace, 23(11), 1847-1859. Oxford University Press Gatta, G, Sobota, V, Citerni, C, Diness, J G, Sørensen, U S, Jespersen, T, Bentzen, B H, Zeemering, S, Kuiper, M, Verheule, S, Schotten, U & Van Hunnik, A 2021, ' Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction ', Europace, vol. 23, no. 11, pp. 1847-1859 . https://doi.org/10.1093/europace/euab125 Europace |
| ISSN: | 1099-5129 |
| DOI: | 10.1093/europace/euab125 |
| Popis: | Aims Pharmacological termination of atrial fibrillation (AF) remains a challenge due to limited efficacy and potential ventricular proarrhythmic effects of antiarrhythmic drugs. SK channels are proposed as atrial-specific targets in the treatment of AF. Here, we investigated the effects of the new SK channel inhibitor AP14145. Methods and results Eight goats were implanted with pericardial electrodes for induction of AF (30 days). In an open-chest study, the atrial conduction velocity (CV) and effective refractory period (ERP) were measured during pacing. High-density mapping of both atrial free-walls was performed during AF and conduction properties were assessed. All measurements were performed at baseline and during AP14145 infusion [10 mg/kg/h (n = 1) or 20 mg/kg/h (n = 6)]. At an infusion rate of 20 mg/kg/h, AF terminated in five of six goats. AP14145 profoundly increased ERP and reduced CV during pacing. AP14145 increased spatiotemporal instability of conduction at short pacing cycle lengths. Atrial fibrillation cycle length and pathlength (AF cycle length × CV) underwent a strong dose-dependent prolongation. Conduction velocity during AF remained unchanged and conduction patterns remained complex until the last seconds before AF termination, during which a sudden and profound organization of fibrillatory conduction occurred. Conclusion AP14145 provided a successful therapy for termination of persistent AF in goats. During AF, AP14145 caused an ERP and AF cycle length prolongation. AP14145 slowed CV during fast pacing but did not lead to a further decrease during AF. Termination of AF was preceded by an abrupt organization of AF with a decline in the number of fibrillation waves. |
| Databáze: | OpenAIRE |
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