NEUROCIRCULATORY RESPONSES IN OBSTRUCTIVE SLEEP APNEA

首席调查员(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。本课题的主要目的是观察交感神经阻断在阻塞性睡眠呼吸暂停综合征中的作用，以及鼻腔持续正压治疗对交感神经兴奋的影响。阻塞性睡眠呼吸暂停综合症是一种影响4%的男性和2%的女性的综合症。老年人的患病率甚至可能更高。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。阻塞性睡眠呼吸暂停综合征的一个关键生理异常是交感神经张力升高，这可能是心血管发病率的基础。阻塞性睡眠呼吸暂停综合征与动脉压波动有关。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增加所致。我们实验室使用时间序列分析的初步数据表明，OSA患者在呼吸暂停期间出现的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断对屏气和米勒动作的神经循环反应的影响。这项研究表明，交感神经阻断基本上取消了MSNA和AP的反应，从而暗示了一种因果关系。为了进一步探讨交感神经放电的激增是否引起血管收缩，我们建议进行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反应，然而，先前没有研究直接检查OSA治疗对交感神经兴奋诱导的血管收缩的影响。这个项目将进一步增加我们对阻塞性睡眠呼吸暂停综合征心血管发病率和死亡率的病理生理机制的了解。PI得到了来自NIH的辛诺威博士R01提案的少数派补充资料的资助。这项提议将为独立调查员提供必要的额外支持和培训。

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.