NEUROCIRCULATORY RESPONSES IN OBSTRUCTIVE SLEEP APNEA

点击翻译按钮获取中文摘要

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.