Dematteis Maurice, Godin-Ribuot Diane, Arnaud Claire, Ribuot Christophe, Stanke-Labesque Françoise, Pépin Jean-Louis, Lévy Patrick
HP2 Laboratory, INSERM ERI17, Université Joseph Fourier, Grenoble, France.
ILAR J. 2009;50(3):262-81. doi: 10.1093/ilar.50.3.262.
Sleep-disordered breathing, and particularly the highly prevalent obstructive sleep apnea syndrome, is a multicomponent disorder combining intermittent hypoxia (IH), sleep fragmentation, and obstructed respiratory efforts. It is frequently associated with comorbidities and leads to numerous complications, including cardiovascular consequences that are conditioned by genetic predisposition and environment. The complexity of the disease and the reduced possibilities for patient investigations, especially at the tissue level, have limited progress in the understanding of sleep apnea pathophysiology and in the development of specific treatments. Animal models make it possible to study the causative mechanisms (essentially upper airway dysfunction) and the consequences (cardiovascular, metabolic, and neurological alterations) of nocturnal respiratory events without the confounding factors that occur in humans. Such studies have revealed some of the pathophysiological mechanisms and enabled the recognition of IH as the most important sleep apnea component underlying cardiovascular complications. We review different animal models used to assess detrimental sleep apnea-related cardiovascular consequences: blood pressure elevation, impaired vasoreactivity, structural arterial remodeling leading to atherosclerosis, cardiac remodeling, and myocardial infarction. We also review experimental evidence of beneficial effects of IH. By combining clinical and experimental research, these models will contribute to the understanding of differential patient susceptibility and to the elaboration of prevention strategies and tailored treatments for sleep apnea patients.
睡眠呼吸紊乱，尤其是高度流行的阻塞性睡眠呼吸暂停综合征，是一种多因素疾病，合并了间歇性缺氧（IH）、睡眠片段化和呼吸努力受阻。它常与合并症相关，并导致许多并发症，包括由遗传易感性和环境所决定的心血管后果。该疾病的复杂性以及患者检查的可能性有限，尤其是在组织层面，这限制了对睡眠呼吸暂停病理生理学的理解以及特定治疗方法的开发。动物模型使得在没有人类中出现的混杂因素的情况下，研究夜间呼吸事件的致病机制（主要是上气道功能障碍）及其后果（心血管、代谢和神经改变）成为可能。此类研究揭示了一些病理生理机制，并使人们认识到IH是睡眠呼吸暂停导致心血管并发症的最重要组成部分。我们综述了用于评估与睡眠呼吸暂停相关的有害心血管后果的不同动物模型：血压升高、血管反应性受损、导致动脉粥样硬化的结构性动脉重塑、心脏重塑和心肌梗死。我们还综述了IH有益作用的实验证据。通过结合临床和实验研究，这些模型将有助于理解患者的不同易感性，并有助于制定睡眠呼吸暂停患者的预防策略和个性化治疗方案。
