CIRCULATORY CONTROL DURING HYPOXEMIA

主要研究者的长期目标是检查机制 控制外周血流量 该提案检查了动脉 化学反射（交感神经兴奋性），其通过肺机械反射的调节 低氧血症对中枢神经系统（交感神经抑制）和外周血管的影响 人类 我们的假设是：1）在低氧血症（自发性 交感血管收缩剂运输和去甲肾上腺素（NE） 从神经末梢的释放增加，但肾上腺素能血管收缩 不会发生，前臂血管阻力降低。 上涨 血浆NE减弱是因为在低氧血症期间NE清除率升高。 使用 一种氚化NE输注技术，我们将探讨 低氧血症时NE清除率增加。 2)前臂血管舒张 在低氧血症期间观察到的这一现象不是由于交感神经退缩， 可能继发于胆碱能血管扩张和/或局部血管扩张剂 机制等 在动脉内注射阿托品的实验中， （胆碱能阻断）和氨茶碱（腺苷受体阻断），我们 将探讨低氧血症引起血管舒张的机制。 3)的 通气的交感神经抑制作用在对抗 由低氧血症引起的交感神经兴奋。 我们将测量交感神经肌肉 神经活动（MSNA，腓神经显微神经造影）和前臂及皮肤血 流动（体积描记术，激光多普勒测速仪），以检查的影响， 改变呼吸与/不同时化学感受器刺激。 四、 周期性呼吸，如阻塞性睡眠呼吸暂停患者， 伴随着显著的血液动力学振荡。 显著血压 呼吸暂停后立即发生升高，可能部分由 低氧血症或缺乏肺机械反射活动（呼吸暂停）。 确定 交感神经系统在这种反应中的作用，我们将测量 模拟呼吸暂停（自主屏气）期间的MSNA和 睡眠（自发）。 周期性（Cheyne-Stokes）呼吸也非常 常见于心力衰竭，尤其是在睡眠中。 如果心力衰竭， 发生类似于睡眠呼吸暂停的血液动力学振荡，这些间歇性 左心室后负荷增加可能进一步损害循环功能， 功能 为了确定这些反射在心脏中是否重要， 如果失败，我们将在这些患者中进行显微神经造影研究。 这些研究将在活跃的临床研究环境中进行 采用多学科方法。 这些发现将提供新的见解 循环控制的机制，并可能有重要的意义 疾病。

The long range goal of the principal investigator is to examine mechanisms that control peripheral blood flow. This proposal examines the arterial chemoreflex (sympathoexcitatory), its modulation by the lung mechanoreflex (sympathoinhibitory) and peripheral vascular effects of hypoxemia in humans. Our hypotheses are that 1) During hypoxemia (with spontaneous breathing) sympathetic vasoconstrictor traffic and norepinephrine (NE) release from nerve terminals is increased, yet adrenergic vasoconstriction does not occur and forearm vascular resistance decreases. The rise in plasma NE is attenuated because NE clearance rises during hypoxemia. Using a tritiated NE infusion technique, we will explore the mechanism of increased NE clearance during hypoxemia. 2) The forearm vasodilation observed during hypoxemia is not due to sympathetic neural withdrawal but may be secondary to cholinergic vasodilation and/or local vasodilator mechanisms. In experiments with intra-arterial infusion of atropine (cholinergic blockade) and aminophylline (adenosine receptor blockade) we will explore the mechanism(s) of vasodilation induced by hypoxemia. 3) The sympathoinhibitory effect of ventilation is crucial in opposing sympathoexcitation evoked by hypoxemia. We will measure muscle sympathetic nerve activity (MSNA, peroneal microneurography) and forearm and skin blood flow (plethysmography, laser Doppler velocimetry) to examine the effects of altered breathing with/without simultaneous chemoreceptor stimulation. 4) Periodic breathing, such as seen in patients with obstructive sleep apnea, is accompanied by striking hemodynamic oscillations. Marked blood pressure elevations occur immediately after apnea and may in part be mediated by hypoxemia or absent lung mechanoreflex activity (apnea). To determine the role of the sympathetic nervous system in this response, we will measure MSNA during simulated apnea (voluntary breathholding), and apnea during sleep (spontaneous). Periodic (Cheyne-Stokes) breathing is also very common in heart failure, especially during sleep. If in heart failure, hemodynamic oscillations similar to sleep apnea occur, these intermittent increases in left ventricular afterload may further impair circulatory function. To determine whether these reflexes are important in heart failure, we will perform microneurography studies in these patients. These studies will be conducted in an active clinical research environment using a multidisciplinary approach. The findings will provide new insight into mechanisms of circulatory control and may have important implications in disease.