Basic/Translational Science -> Whole Animal Electrophysiology and Pharmacology (includes Neurohumoral Modulation) D-PO06 - Poster Session VI (ID 26) Poster

D-PO06-010 - Acetylcholine-regulated Potassium Channel-inhibition Protects From Obstructive Sleep Apnea Associated Atrial Arrhythmogenic Changes In Rats (ID 639)

 B. Linz: Nothing relevant to disclose.


Background: Obstructive sleep apnea (OSA) is associated with intermittent hypoxemia and intrathoracic pressure fluctuations which may trigger vagal activity, leading to an increased acetylcholine-regulated potassium current (IK,ACh).
Objective: Here we elucidated acute atrial electrophysiological effects of obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) and the role of atrial IKACh activation.
Methods: In sedated spontaneously breathing rats (2% isoflurane), either IK,ACh-inhibitor (XAF-1407: 1mg/kg) or a buffer-based vehicle was perfused (Control). INAP was applied non-invasively by a negative pressure device 14 times throughout 70 minutes. Simulated apneas were maintained for one minute with a four minute resting period. Atrial effective refractory period (AERP), inducible atrial fibrillation (AF)-durations and atrial activation time were acquired by a programmed atrial pacing protocol before, during and after applied INAP throughout the study.
Results: During single INAP applications atrial activation times prolonged transiently in both groups (Control: INAP vs. pre-INAP p=0.034; XAF-1407: INAP vs. pre-INAP p=0.039). In control-rats, seventy minutes of repetitive INAP prolonged P-wave duration (+10.8±2.7% vs. baseline, p=0.008) and decreased AERP by 14.6±3.1% (vs. baseline p=0.001). AERP shortening correlated with the cumulative pressure applied per body weight (Pearson r= -0.773; p= 0.025). XAF-1407 could prevent P-wave prolongation and AERP shortening. Inducible AF-durations (CTR 0.94±0.34s vs. XAF-1407 0.1±0.09s p=0.049) were shorter in XAF-1407 treated rats. Drops in oxygen saturation or applied INAP were comparable in control and XAF-1407 rats.
Conclusion: Short-term simulated OSA is associated with AF-related arrhythmogenic changes, which could be prevented by pharmacological IK,ACh inhibition. Moreover, the cumulative negative airway pressure applied determined aERP shortening and may represent a target for OSA treatment. These findings have important implications for the antiarrhythmic management of AF patients with OSA.