Faculty of Health and Medical Sciences, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark; Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.
Klinik für Innere Medizin III, Universität des Saarlandes, Homburg/Saar, Germany.
Heart Rhythm. 2021 Mar;18(3):455-464. doi: 10.1016/j.hrthm.2020.10.011. Epub 2020 Oct 17.
High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways.
We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate.
INAP (48 events/4 h; apnea-hypopnea index 12 events/h) was applied in sedated spontaneously breathing rats (2% isoflurane) to simulate mild-to-moderate OSA. Rats without INAP served as a control group (CTR). In an acute test series (ATS), rats were either killed immediately (n = 9 per group) or after 24 hours of recovery (ATS-REC: n = 5 per group). To simulate high night-to-night variability in OSA, INAP applications (n = 10; 24 events/4 h; apnea-hypopnea index 6/h) were repeated every second day for 3 weeks in a chronic test series (CTS).
INAP increased atrial oxidative stress acutely, represented in decreases of reduced to oxidized glutathione ratio (ATS: INAP: 0.33 ± 0.05 vs CTR: 1 ± 0.26; P = .016), which was reversible after 24 hours (ATS-REC: INAP vs CTR; P = .274). Although atrial oxidative stress did not accumulate in the CTS, atrial histological analysis revealed increased cardiomyocyte diameters, reduced connexin 43 expression, and increased interstitial fibrosis formation (CTS: INAP 7.0% ± 0.5% vs CTR 5.1% ± 0.3%; P = .013), which were associated with longer inducible AF episodes (CTS: INAP: 11.65 ± 4.43 seconds vs CTR: 0.7 ± 0.33 seconds; P = .033).
Acute simulation of OSA was associated with reversible atrial oxidative stress. Cumulative exposure to these transient OSA-related conditions resulted in AF substrates and was associated with increased AF susceptibility. Mild-to-moderate OSA with high night-to-night variability may deserve intensive management to prevent atrial substrate development.
阻塞性睡眠呼吸暂停（OSA）的夜间变异性高与心房颤动（AF）有关。阻塞性呼吸暂停的特点是在无效吸气期间间歇性缺氧-复氧和胸内压力波动，上呼吸道阻塞。
我们阐明了反复暴露于间歇性负压上气道压力（INAP）模拟的短暂 OSA 条件对 AF 底物发展的影响。
在镇静、自主呼吸的大鼠（2%异氟烷）中施加 INAP（48 次/4 小时；每小时呼吸暂停-低通气指数 12 次），模拟轻度至中度 OSA。未接受 INAP 的大鼠作为对照组（CTR）。在急性测试系列（ATS）中，大鼠要么立即处死（每组 9 只），要么在恢复 24 小时后处死（ATS-REC：每组 5 只）。为了模拟 OSA 夜间变异性高，在慢性测试系列（CTS）中，每隔一天重复施加 INAP 应用（n = 10；4 小时 24 次；每小时呼吸暂停-低通气指数 6 次），共 3 周。
INAP 急性增加心房氧化应激，表现为还原型谷胱甘肽与氧化型谷胱甘肽比值降低（ATS：INAP：0.33 ± 0.05 与 CTR：1 ± 0.26；P =.016），24 小时后可恢复（ATS-REC：INAP 与 CTR；P =.274）。尽管 CTS 中心房氧化应激没有累积，但心房组织学分析显示心肌细胞直径增大，连接蛋白 43 表达减少，间质纤维化形成增加（CTS：INAP 7.0% ± 0.5%与 CTR 5.1% ± 0.3%；P =.013），这与可诱导性 AF 发作时间延长有关（CTS：INAP：11.65 ± 4.43 秒与 CTR：0.7 ± 0.33 秒；P =.033）。
OSA 的急性模拟与可逆性心房氧化应激有关。累积暴露于这些与 OSA 相关的短暂条件下会导致 AF 底物形成，并与 AF 易感性增加有关。夜间变异性高的轻度至中度 OSA 可能需要加强管理，以防止心房底物的发展。
