NEUROCIRCULATORY RESPONSES IN OBSTRUCTIVE SLEEP APNEA

首席研究员（PI）的长期目标是检查阻塞性睡眠呼吸暂停（OSA）和其他影响老年人的疾病过程中的自主神经反应。本项目的主要目的是检查交感神经阻滞在OSA中的作用，并确定鼻腔持续气道正压（nCPAP）治疗对交感神经兴奋的有效性。阻塞性睡眠呼吸暂停综合症影响了4%的男性和2%的女性。在老年人中患病率可能更高。与阻塞性睡眠呼吸暂停相关的疾病包括高血压（HTN）、心肌梗死（MI）、心律失常、中风和过早死亡。OSA的一个关键生理异常是交感神经张力增高，这可能是心血管疾病的基础。阻塞性睡眠呼吸暂停与动脉压振荡有关。动脉压的升高可能是由于交感神经活动增强导致血管收缩神经流量的增加。我们实验室使用时间序列分析的初步数据表明，在OSA呼吸暂停期间观察到的MSNA和动脉压（AP）反应伴随着血管收缩。最近一项涉及正常受试者的研究调查了交感神经阻滞对屏住呼吸和穆勒操作的神经循环反应的影响。本研究表明，交感神经阻滞基本上消除了MSNA和AP反应，从而表明两者之间存在因果关系。为了进一步探讨交感放电的激增是否会引起血管收缩，我们提出了肾上腺素能阻断研究。此外，有证据表明，OSA治疗可减弱对呼吸暂停的交感神经反应，然而，尚无先前的研究直接检测OSA治疗对交感神经兴奋诱导的血管收缩的影响。该项目将进一步增加我们对OSA中心血管疾病发病率和死亡率的病理生理机制的认识。该项目由NIH对Sinoway博士的R01提案的少数派补充资助。该提案将为私家侦探提供额外的支持和必要的培训，使其成为一名独立的受资助调查员。

The long term goal of the Principal Investigator (PI) is to examine autonomic responses in obstructive sleep apnea (OSA) and in other disease processes that affect the aged. The main objective of this project is to examine the effect of sympathetic blockade in OSA and to determine the effectiveness of nasal continuous positive airway pressure (nCPAP) therapy on sympathoexcitation. OSA is a syndrome that affects 4 percent of men and 2 percent of women. The prevalence may even be higher in the elderly. Morbidities associated with obstructive sleep apnea include hypertension (HTN), myocardial infarction (MI), cardiac arrhythmias, strokes and premature death. A key physiologic abnormality in OSA is heightened sympathetic tone which may underlie the cardiovascular morbidity. OSA is associated with arterial pressure oscillations. The increase in arterial pressure may be due to an increase in vasoconstrictor nerve traffic from heightened sympathetic activity. Preliminary data from our lab using time sequence analysis suggest that the MSNA and arterial pressure (AP) responses seen during apnea in OSA are accompanied by vasoconstriction. A recent study involving normal subjects investigated the effects of sympathetic blockade on neurocirculatory responses to breath-holds and the Mueller maneuver. This study demonstrated that sympathetic blockade essentially abolished MSNA and AP responses thus suggesting a causal relationship. To further explore whether surges in sympathetic discharge evokes vasoconstriction, we propose adrenergic blocking studies. Additionally, evidence suggests that treatment of OSA attenuates the sympathetic response to apneas, however, there are no prior studies that directly examined the effects of OSA therapy on sympathoexcitation - induced vasoconstriction. This project will further increase our knowledge of the pathophysiologic mechanisms responsible for the cardiovascular morbidity and mortality seen in OSA. The PI has been funded by a Minority Supplement to Dr. Sinoway's R01 proposal from the NIH. This proposal will give the PI the additional support and training necessary to become an independent funded investigator.