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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.

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AimTo propose a standardized workflow for 3D-electroanatomical mapping guided pulmonary vein isolation in pigs.Materials and methodsDanish female landrace pigs were anaesthetized. Ultrasound-guided puncture of both femoral veins was performed and arterial access for blood pressure measurement established. Fluoroscopy- and intracardiac ultrasound-guided passage of the patent foramen ovale or transseptal puncture was performed. Then, 3D-electroanatomical mapping of the left atrium was conducted using a high-density mapping catheter. After mapping all pulmonary veins, an irrigated radiofrequency ablation catheter was used to perform ostial ablation to achieve electrical pulmonary vein isolation. Entrance- and exit-block were confirmed and re-assessed after a 20-min waiting period. Lastly, animals were sacrificed to perform left atrial anatomical gross examination.ResultsWe present data from 11 consecutive pigs undergoing pulmonary vein isolation. Passage of the fossa ovalis or transseptal puncture was uneventful and successful in all animals. Within the inferior pulmonary trunk 2–4 individual veins as well as 1–2 additional left and right pulmonary veins could be cannulated. Electrical isolation by point-by-point ablation of all targeted veins was successful. However, pitfalls including phrenic nerve capture during ablation, ventricular arrhythmias during antral isolation close to the mitral valve annulus and difficulties in accessing right pulmonary veins were encountered.ConclusionFluoroscopy- and intracardiac ultrasound-guided transseptal puncture, high-density electroanatomical mapping of all pulmonary veins and complete electrical pulmonary vein isolation can be achieved reproducibly and safely in pigs when using current technologies and a step-by-step approach.