CIRCULATORY CONTROL DURING HYPOXEMIA

首席研究员的长期目标是检查机制。 它控制着周围的血液流动。这项建议检查了动脉 化学反射(交感兴奋)及其受肺机械反射的调节 (交感神经抑制)和低氧血症的外周血管效应 人类。我们的假设是：1)在低氧血症期间(自发性 交感血管收缩交通和去甲肾上腺素(NE) 神经末梢释放增加，但肾上腺素能血管收缩 不会发生，前臂血管阻力降低。中国经济的崛起 血浆去甲肾上腺素降低是因为低氧血症时去甲肾上腺素清除量升高。vbl.使用 一种新型的去甲肾上腺素输注技术，我们将探讨其机制。 低氧血症时NE清除量增加。2)前臂血管扩张 在低氧血症中观察到的不是由于交感神经退缩，而是 可能继发于胆碱能血管扩张和/或局部血管扩张 机械装置。在动脉内注入阿托品的实验中 (胆碱能受体阻滞剂)和氨茶碱(腺苷受体阻滞剂) 将探讨(S)低氧血症引起血管扩张的机制。3) 呼吸的交感神经抑制作用是对抗 低氧血症引起的交感神经兴奋。我们将测量肌肉交感神经 神经活动(MSNA、腓神经显微照相术)和前臂及皮肤血 血流(体积描记术、激光多普勒测速仪)检查的效果 在有/没有同时化学感受器刺激的情况下改变呼吸。4) 周期性呼吸，例如阻塞性睡眠呼吸暂停患者的呼吸， 伴随着显著的血流动力学波动。标示血压 呼吸暂停后立即发生抬高，并可能部分地通过 低氧血症或缺乏肺机械反射活动(呼吸暂停)。要确定 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(自愿屏气)和呼吸暂停期间的MSNA 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。如果是心力衰竭， 类似睡眠呼吸暂停的血液动力学振荡会发生，这些间歇性 左心室后负荷增加可能进一步损害循环 功能。以确定这些反射对心脏是否重要 如果失败，我们将对这些患者进行显微神经学检查。 这些研究将在积极的临床研究环境中进行。 使用多学科方法。这些发现将提供新的见解 循环控制的机制，并可能具有重要的意义 在疾病中。

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.