Academic Journal
The K Ca 2 Channel Inhibitor AP30663 Selectively Increases Atrial Refractoriness, Converts Vernakalant-Resistant Atrial Fibrillation and Prevents Its Reinduction in Conscious Pigs
| العنوان: | The K Ca 2 Channel Inhibitor AP30663 Selectively Increases Atrial Refractoriness, Converts Vernakalant-Resistant Atrial Fibrillation and Prevents Its Reinduction in Conscious Pigs |
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| المؤلفون: | Diness, Jonas Goldin, Kirchhoff, Jeppe Egedal, Speerschneider, Tobias, Abildgaard, Lea, Edvardsson, Nils, Sorensen, Ulrik S., Grunnet, Morten, Bentzen, Bo Hjorth |
| المصدر: | Diness , J G , Kirchhoff , J E , Speerschneider , T , Abildgaard , L , Edvardsson , N , Sorensen , U S , Grunnet , M & Bentzen , B H 2020 , ' The K Ca 2 Channel Inhibitor AP30663 Selectively Increases Atrial Refractoriness, Converts Vernakalant-Resistant Atrial Fibrillation and Prevents Its Reinduction in Conscious Pigs ' , Frontiers in Pharmacology , vol. 11 , 159 . https://doi.org/10.3389/fphar.2020.00159 |
| سنة النشر: | 2020 |
| المجموعة: | University of Copenhagen: Research / Forskning ved Københavns Universitet |
| مصطلحات موضوعية: | atrial fibrillation, ion channels, antiarrhythmic drugs, SK channels, K(Ca)2, POTASSIUM SK CHANNELS, HYDROCHLORIDE, VARIANTS, COMMON, LOCI |
| الوصف: | Aims To describe the effects of the K(Ca)2 channel inhibitor AP30663 in pigs regarding tolerability, cardiac electrophysiology, pharmacokinetics, atrial functional selectivity, effectiveness in cardioversion of tachy-pacing induced vernakalant-resistant atrial fibrillation (AF), and prevention of reinduction of AF. Methods and Results 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 mu M of AP30663, which was achieved at a dose level of 5 mg/kg. Conclusion AP30663 has shown properties in animals that would be of clinical interest in man. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| DOI: | 10.3389/fphar.2020.00159 |
| الاتاحة: | https://researchprofiles.ku.dk/da/publications/the-kca2-channel-inhibitor-ap30663-selectively-increases-atrial-refractoriness-converts-vernakalantresistant-atrial-fibrillation-and-prevents-its-reinduction-in-conscious-pigs(5caf0664-6a13-4fba-892d-fa7c889b5ada).html https://doi.org/10.3389/fphar.2020.00159 https://curis.ku.dk/ws/files/247215261/OA_The_K_Ca_2_Channel_Inhibitor_AP30663_Selectively_Increases_Atrial_Refractoriness_Converts_Vernakalant_Resistant_Atrial_Fibrillation_and_Prevents_Its_Reinduction_in_Conscious_Pigs.pdf |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.ECDD8109 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fphar.2020.00159 |
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