Academic Journal
Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events
| العنوان: | Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events |
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| المؤلفون: | Linz, Benedikt, Hesselkilde, Eva M, Skarsfeldt, Mark A, Hertel, Julie N, Sattler, Stefan M, Yan, Yannan, Tfelt-Hansen, Jacob, Diness, Jonas G, Bentzen, Bo H, Linz, Dominik, Jespersen, Thomas |
| المصدر: | Linz , B , Hesselkilde , E M , Skarsfeldt , M A , Hertel , J N , Sattler , S M , Yan , Y , Tfelt-Hansen , J , Diness , J G , Bentzen , B H , Linz , D & Jespersen , T 2023 , ' Pharmacological inhibition of SK-channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events ' , Journal of Cardiovascular Electrophysiology , vol. 34 , no. 1 , pp. 126-134 . https://doi.org/10.1111/jce.15769 |
| سنة النشر: | 2023 |
| المجموعة: | Maastricht University Research Publications |
| الوصف: | BACKGROUND: Obstructive sleep apnea (OSA) creates a complex substrate for atrial fibrillation (AF), which is refractory to many clinically available pharmacological interventions. We investigated atrial antiarrhythmogenic properties and ventricular electrophysiological safety of small-conductance Ca2+ -activated K+ (SK)-channel inhibition in a porcine model for obstructive respiratory events. METHODS: In spontaneously breathing pigs, obstructive respiratory events were simulated by intermittent negative upper airway pressure (INAP) applied via a pressure device connected to the intubation tube. INAP was applied for 75 s, every 10 min, three times before and three times during infusion of the SK-channel inhibitor AP14145. Atrial effective refractory periods (AERP) were acquired before (pre-INAP), during (INAP) and after (post-) INAP. AF-inducibility was determined by a S1S2 atrial pacing protocol. Ventricular arrhythmicity was evaluated by heart rate adjusted QT-interval duration (QT-paced) and electromechanical window (EMW) shortening. RESULTS: During vehicle infusion, INAP transiently shortened AERP (pre-INAP: 135 ± 10 ms vs. post-INAP 101 ± 11 ms; p = .008) and increased AF-inducibility. QT-paced prolonged during INAP (pre-INAP 270 ± 7 ms vs. INAP 275 ± 7 ms; p = .04) and EMW shortened progressively throughout INAP and post-INAP (pre-INAP 80 ± 4 ms; INAP 59 ± 6 ms, post-INAP 46 ± 10 ms). AP14145 prolonged baseline AERP, partially prevented INAP-induced AERP-shortening and reduced AF-susceptibility. AP14145 did not alter QT-paced at baseline (pre-AP14145 270 ± 7 ms vs. AP14145 268 ± 6 ms, p = .83) or QT-paced and EMW-shortening during INAP. CONCLUSION: In a pig model for obstructive respiratory events, the SK-channel-inhibitor AP14145 prevented INAP-associated AERP-shortening and AF-susceptibility without impairing ventricular electrophysiology. Whether SK-channels represent a target for OSA-related AF in humans warrants further study. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | https://cris.maastrichtuniversity.nl/en/publications/9e42aad1-780c-4d51-abca-e05b874459a8 |
| DOI: | 10.1111/jce.15769 |
| الاتاحة: | https://cris.maastrichtuniversity.nl/en/publications/9e42aad1-780c-4d51-abca-e05b874459a8 https://doi.org/10.1111/jce.15769 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6762C78 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1111/jce.15769 |
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