Arrhythmogenic mechanisms of acute obstructive respiratory events in a porcine model of drug-induced long QT.

Autor:	Linz B; Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: bene.linz@sund.ku.dk., Sattler SM; Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Flethøj M; Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Høtbjerg Hansen ME; Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Hesselkilde EM; Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Saljic A; Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Wirth K; Sanofi, Frankfurt, Germany., Linz D; Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Centre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia; Department of Cardiology, Maastricht University Medical Centre, Maastricht, The Netherlands., Tfelt-Hansen J; Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Denmark., Jespersen T; Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Heart rhythm [Heart Rhythm] 2021 Aug; Vol. 18 (8), pp. 1384-1391. Date of Electronic Publication: 2021 Mar 15.
DOI:	10.1016/j.hrthm.2021.03.017
Abstrakt:	Background: Obstructive sleep apnea is associated with increased risk of sudden cardiac death. Objective: The purpose of this study was to elucidate changes in ventricular repolarization and electromechanical interaction during obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) in pigs. We also investigated the effect of a reduced repolarization reserve in drug-induced long QT (LQT) following INAP-induced changes in ventricular repolarization. Methods: In sedated spontaneously breathing pigs, 75 seconds of INAP was applied by a negative pressure device connected to the endotracheal tube. Ventricular electromechanical coupling was determined by the electromechanical window (EMW) before (pre-INAP), during (INAP), and after INAP (post-INAP). Incidence rates of premature ventricular contractions (PVCs) were measured respectively. A drug-induced LQT was modeled by treating the pigs with the hERG1 blocker dofetilide (DOF). Results: Whereas QT interval increased during and decreased after INAP (pre-INAP: 273 ± 5 ms; INAP 281 ± 6 ms; post-INAP 254 ± 9 ms), EMW shortened progressively throughout INAP and post-INAP periods (pre-INAP 81 ± 4 ms; post-INAP 44 ± 7 ms). DOF shortened EMW at baseline. Throughout INAP, EMW decreased in a comparable fashion as before DOF (pre-INAP/+DOF 61 ± 7 ms; post-INAP/+DOF 14 ± 9 ms) but resulted in shorter absolute EMW levels. Short EMW levels were associated with increased occurrence of PVCs (pre-INAP 7 ± 2 ms vs post-INAP 26 ± 6 ms; P = .02), which were potentiated in DOF pigs (pre-INAP/+DOF 5 ± 2 ms vs post-INAP/+DOF 40 ± 8 ms; P = .006). Administration of atenolol prevented post-INAP EMW shortening and decreased occurrence of PVCs. Conclusion: Transient dissociation of ventricular electromechanical coupling during simulated obstructive respiratory events creates a dynamic ventricular arrhythmogenic substrate, which is sympathetically mediated and aggravated by drug-induced LQT. (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu