Background: Obstructive sleep apnea (OSA) is associated with impaired ventricular hemodynamic and electrophysiological properties and increased risk of sudden cardiac death. We aimed to elucidate changes in electromechanical interaction during obstructive respiratory events in pigs simulated by intermittent negative upper airway pressure (INAP) or intermittent hypoxemic (IH) events. Moreover, we investigated the effect of a reduced repolarization reserve, in a drug-induced Long-QT-syndrome (LQTS), on INAP/IH induced changes in ventricular repolarization.

Methods: In sedated spontaneously breathing pigs, 75 seconds of INAP or IH were applied by a negative pressure device connected to the intubation tube. Electromechanical interaction was determined by QT-duration, left ventricular (LV-) systole-duration and the electromechanical window (EMW: time delay between end of the T-wave and end of left ventricular pressure signal) before (Pre-INAP/-IH), during (INAP/-IH) and after INAP/IH (Post-INAP/-IH). Incidence of premature ventricular contractions (PVC) was measured respectively. To simulate acquired LQTS and thus a condition of a reduced repolarization reserve, animals were treated with hERG1 blocker dofetilide (DOF, 50 µg/kg bodyweight).

Results: Whereas QT-interval increased during and decreased after INAP (Pre-INAP: 273±5ms; INAP: 281±6ms; Post-INAP: 254±9ms), left ventricular systole-duration decreased progressively throughout INAP. EMW shortened steadily throughout INAP and Post-INAP periods (Pre-INAP: 81±4ms; INAP: 58±5ms; Post-INAP: 44±7ms). In DOF-pigs, QT-duration prolonged and LV-systole-duration decreased due to INAP in a similar fashion as throughout vehicle perfusion, resulting in an overall more pronounced INAP-associated EMW-decrease (Pre-INAP/+DOF: 61±7ms; INAP/+DOF: 38±9ms; Post-INAP/+DOF: 14±9ms).

Shortening in EMW was associated with increased occurrence of PVCs (Pre-INAP 7±2 vs. Post-INAP 26±6; p=0.0186), which were potentiated in DOF-pigs (Pre-INAP/+DOF 5±2 vs. Post-INAP/+DOF 40±8; p=0.0056). Administration of atenolol prevented Post-INAP-associated shortening of the LV-systole-duration and the EMW and decreased occurrence of PVCs. While oxygen desaturations were comparable in INAP and IH, IH resulted neither in EMW-shortening nor increases of PVCs.

Conclusion: In pigs, transient complex dissociation of ventricular electromechanical coupling during simulated obstructive respiratory events, but not during IH, creates a dynamic and sympathetically mediated ventricular arrhythmogenic substrate, which is aggravated by drug-induced LQTS.