Pharmacological inhibition of SK‐channels with AP14145 prevents atrial arrhythmogenic changes in a porcine model for obstructive respiratory events

Figures

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  Figure 1. Experimental protocol and representative traces: (A) Overview of experimental protocol. (B) Representative traces throughout 75 s of INAP. Start and end of INAP indicated by arrows in the traces for “Upper airway pressure”. Thiry seconds after INAP‐onset (start in airway pressure fluctuation and first arrow) an atrial effective refractory period was determined. Here, a measurement related coupling stimulus (S2) initiated atrial fibrillation (arrow in MAP channel). SpO2 dropped with a slight delay after INAP‐onset, but recovered within 2 min after INAP. Atrial MAP, atrial monophasic action potential recording; CVP, central venous pressure; ECG—a‐p, electrocardiogram anterior–posterior axis; INAP, intermittent negative upper airway pressure; SpO2, oxygen saturation.

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  Figure 2. Atrial arrhythmogenic effects: INAP associated progressive shortening of atrial effective refractory period (AERP) (A) and action potential duration at 90% repolarization (APD90) during vehicle (B). After administration of AP14145, neither AERP (C) nor APD90 (D) shortened INAP‐related. Intermittent negative upper airway pressure (INAP). Data are expressed as mean ± SEM. For statistical analysis, a one‐way analysis of variance followed by Tukey's multiple comparison test was applied.

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  Figure 3. Atrial fibrillation inducibility by extra‐stimuli. (A) Representative traces of an atrial refractory measurement with a train of eight S1 stimuli and a shorter coupling stimulus (S2), which induced atrial fibrillation (AF). (B) AF‐inducibility pre‐INAP and INAP during vehicle and AP14145. (C) Comparison of INAP‐related AF‐inducibility before and after AP14145. Intermittent negative upper airway pressure (INAP). Data are presented as mean ± SEM. For statistical analysis, a paired t‐test was applied.

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  Figure 4. Ventricular electrophysiological effects: Dynamic QT‐interval duration while fixed atrial pacing (QT‐paced) pre‐INAP, INAP and post‐INAP, during vehicle (A) and AP14145 (B). Changes in ventricular electromechanical window (EMW) pre‐INAP, INAP and post‐INAP, during vehicle (C) and AP14145 (D). Intermittent negative upper airway pressure (INAP). Data are expressed as mean ± SEM. For statistical analysis, a one‐way analysis of variance followed by Tukey's multiple comparison test was applied.