Jordan Amy S, McEvoy R Doug, Edwards Jill K, Schory Karen, Yang Chang-Kook, Catcheside Peter G, Fogel Robert B, Malhotra Atul, White David P
Brigham and Women's Hospital, Sleep Disorders Research Program @ BIDMC, 75 Francis Street, Boston, MA 02115, USA.
J Physiol. 2004 Aug 1;558(Pt 3):993-1004. doi: 10.1113/jphysiol.2004.064238. Epub 2004 Jun 24.
The termination of obstructive respiratory events is typically associated with arousal from sleep. The ventilatory response to arousal may be an important determinant of subsequent respiratory stability/instability and therefore may be involved in perpetuating obstructive respiratory events. In healthy subjects arousal is associated with brief hyperventilation followed by more prolonged hypoventilation on return to sleep. This study was designed to assess whether elevated sleeping upper airway resistance (R(UA)) alters the ventilatory response to arousal and subsequent breathing on return to sleep in patients with obstructive sleep apnoea (OSA). Inspired minute ventilation (V(I)), R(UA) and end-tidal CO(2) pressure (P(ET,CO(2))) were measured in 22 patients (11 men, 11 women) with OSA (mean +/-s.e.m., apnoea-hypopnoea index (AHI) 48.9 +/- 5.9 events h(-1)) during non-rapid eye movement (NREM) sleep with low R(UA) (2.8 +/- 0.3 cmH(2)O l(-1) s; optimal continuous positive airway pressure (CPAP) = 11.3 +/- 0.7 cmH(2)O) and with elevated R(UA) (17.6 +/- 2.8 cmH(2)O l(-1) s; sub-optimal CPAP = 8.4 +/- 0.8 cmH(2)O). A single observer, unaware of respiratory data, identified spontaneous and tone-induced arousals of 3-15 s duration preceded and followed by stable NREM sleep. V(I) was compared between CPAP levels before and after spontaneous arousal in 16 subjects with tone-induced arousals in both conditions. During stable NREM sleep at sub-optimal CPAP, P(ET,CO(2)) was mildly elevated (43.5 +/- 0.8 versus 42.5 +/- 0.8 Torr). However, baseline V(I) (7.8 +/- 0.3 versus 8.0 +/- 0.3 l min(-1)) was unchanged between CPAP conditions. For the first three breaths following arousal, V(I) was higher for sub-optimal than optimal CPAP (first breath: 11.2 +/- 0.9 versus 9.3 +/- 0.6 l min(-1)). The magnitude of hypoventilation on return to sleep was not affected by the level of CPAP and both obstructive and central respiratory events were rare following arousal. Similar results occurred after tone-induced arousals which led to larger responses than spontaneous arousals. V(I) for the first breath following arousal under optimal CPAP was greater in men than women (11.0 +/- 0.4 versus 7.6 +/- 0.6 l min(-1)). These results demonstrate that the ventilatory response to arousal is influenced by pre-arousal airway resistance and gender. Whether this contributes to the perpetuation of respiratory events and the pathogenesis of OSA is unclear.
阻塞性呼吸事件的终止通常与从睡眠中觉醒有关。对觉醒的通气反应可能是随后呼吸稳定性/不稳定性的重要决定因素，因此可能参与了阻塞性呼吸事件的持续发生。在健康受试者中，觉醒与短暂的过度通气相关，随后在重新入睡时会出现更长时间的通气不足。本研究旨在评估睡眠时上气道阻力（R(UA)）升高是否会改变阻塞性睡眠呼吸暂停（OSA）患者对觉醒的通气反应以及重新入睡后的后续呼吸情况。在22例OSA患者（11例男性，11例女性）（平均±标准误，呼吸暂停低通气指数（AHI）为48.9±5.9次/小时）的非快速眼动（NREM）睡眠期间，测量了低R(UA)（2.8±0.3 cmH₂O·l⁻¹·s；最佳持续气道正压通气（CPAP）=11.3±0.7 cmH₂O）和高R(UA)（17.6±2.8 cmH₂O·l⁻¹·s；次优CPAP=8.4±0.8 cmH₂O）时的吸气分钟通气量（V(I)）、R(UA)和呼气末二氧化碳分压（P(ET,CO₂)）。一名不了解呼吸数据的观察者识别出在稳定的NREM睡眠之前和之后持续3 - 15秒的自发和刺激诱发的觉醒。在两种情况下，对16名有刺激诱发觉醒的受试者，比较了自发觉醒前后CPAP水平下的V(I)。在次优CPAP的稳定NREM睡眠期间，P(ET,CO₂)轻度升高（43.5±0.8与42.5±0.8 Torr）。然而，CPAP条件之间的基线V(I)（7.8±0.3与8.0±0.3 l/min）没有变化。在觉醒后的前三呼吸中，次优CPAP时的V(I)高于最佳CPAP（第一呼吸：11.2±0.9与9.3±0.6 l/min）。重新入睡时通气不足的程度不受CPAP水平的影响，觉醒后阻塞性和中枢性呼吸事件都很少见。刺激诱发觉醒后也出现了类似结果，其导致的反应比自发觉醒更大。在最佳CPAP下，觉醒后第一呼吸的V(I)男性大于女性（11.0±0.4与7.6±0.6 l/min）。这些结果表明，对觉醒的通气反应受觉醒前气道阻力和性别的影响。这是否有助于呼吸事件持续发生和OSA的发病机制尚不清楚。
