Pathophysiology of Sleep Apnea

Dempsey JA, Veasey SC, Morgan BJ, O'Donnell CP. Pathophysiology of Sleep Apnea. Physiol Rev 90: 47-112, 2010; doi:10.1152/physrev.00043.2008.-Sleep-induced apnea and disordered breathing refers to intermittent, cyclical cessations or reductions of airflow, with or without obstructions of the upper airway (OSA). In the presence of an anatomically compromised, collapsible airway, the sleep-induced loss of compensatory tonic input to the upper airway dilator muscle motor neurons leads to collapse of the pharyngeal airway. In turn, the ability of the sleeping subject to compensate for this airway obstruction will determine the degree of cycling of these events. Several of the classic neurotransmitters and a growing list of neuromodulators have now been identified that contribute to neurochemical regulation of pharyngeal motor neuron activity and airway patency. Limited progress has been made in developing pharmacotherapies with acceptable specificity for the treatment of sleep-induced airway obstruction. We review three types of major long-term sequelae to severe OSA that have been assessed in humans through use of continuous positive airway pressure (CPAP) treatment and in animal models via long-term intermittent hypoxemia (IH): 1) cardiovascular. The evidence is strongest to support daytime systemic hypertension as a consequence of severe OSA, with less conclusive effects on pulmonary hypertension, stroke, coronary artery disease, and cardiac arrhythmias. The underlying mechanisms mediating hypertension include enhanced chemoreceptor sensitivity causing excessive daytime sympathetic vasoconstrictor activity, combined with overproduction of superoxide ion and inflammatory effects on resistance vessels. 2) Insulin sensitivity and homeostasis of glucose regulation are negatively impacted by both intermittent hypoxemia and sleep disruption, but whether these influences of OSA are sufficient, independent of obesity, to contribute significantly to the "metabolic syndrome" remains unsettled. 3) Neurocognitive effects include daytime sleepiness and impaired memory and concentration. These effects reflect hypoxic-induced "neural injury." We discuss future research into understanding the pathophysiology of sleep apnea as a basis for uncovering newer forms of treatment of both the ventilatory disorder and its multiple sequelae.

登普西JA，维齐SC，摩根BJ，奥唐奈CP。睡眠呼吸暂停的病理生理学。《生理学评论》90：47 - 112，2010年；doi：10.1152/physrev.00043.2008。 - 睡眠诱导的呼吸暂停和呼吸紊乱是指气流间歇性、周期性停止或减少，伴有或不伴有上气道阻塞（阻塞性睡眠呼吸暂停，OSA）。在存在解剖结构受损、易塌陷的气道时，睡眠诱导的对上气道扩张肌运动神经元的代偿性紧张性输入丧失，导致咽部气道塌陷。反过来，睡眠中的个体对这种气道阻塞进行代偿的能力将决定这些事件的循环程度。目前已经确定了几种经典的神经递质以及越来越多的神经调质，它们有助于咽部运动神经元活动和气道通畅性的神经化学调节。在开发对睡眠诱导的气道阻塞具有可接受特异性的药物疗法方面进展有限。我们回顾了通过使用持续气道正压通气（CPAP）治疗在人类中以及通过长期间歇性低氧血症（IH）在动物模型中评估的严重OSA的三种主要长期后遗症：1）心血管方面。证据最有力地支持严重OSA导致白天系统性高血压，对肺动脉高压、中风、冠状动脉疾病和心律失常的影响不太确定。介导高血压的潜在机制包括化学感受器敏感性增强，导致白天交感缩血管活性过度，以及超氧离子过度产生和对阻力血管的炎症作用。2）胰岛素敏感性和血糖调节的内稳态受到间歇性低氧血症和睡眠中断的负面影响，但OSA的这些影响是否足以独立于肥胖对“代谢综合征”有显著贡献仍未确定。3）神经认知方面的影响包括白天嗜睡以及记忆力和注意力受损。这些影响反映了缺氧诱导的“神经损伤”。我们讨论了未来对理解睡眠呼吸暂停病理生理学的研究，以此作为发现呼吸障碍及其多种后遗症的新治疗形式的基础。