DETERMINANTS OF THE VENTILATORY RESPONSE TO HYPOXIA

缺氧通气反应的决定因素

• 批准号: 3335108
• 负责人: NORMAN H EDELMAN
• 金额: $ 26.26万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-01-01 至 1989-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3335108
• 关键词: REM sleep; acidosis; alkalosis; antiadrenergic agents; brain circulation; brain metabolism; cerebral ischemia /hypoxia; chemoreceptors; denervation; deoxyglucose; dopamine; electroencephalography; gamma aminobutyrate; hemodynamics; hypercapnia; hyperpnea; mathematical model; naloxone; neuropharmacology; particle; radiotracer; respiration regulatory center; respiratory muscles; sleep

The ventilatory and cerebrovascular responses to hypoxia provide the major short-term defenses against inadequate oxygen supply to the brain when that supply is threatened in situations as diverse as acute and chronic lung disease, cardiovascular disease and ascent to high altitude. These responses are not independent variables but interact substantially with each other. Four hypotheses regarding the way in which brain blood flow and/or brain tissue hypoxia may interact with respiratory control are proposed. (1) It is proposed that surges of brain blood flow (BBF) during REM sleep decrease respiratory neuronal output by means of reduction of PCO2 at the central chemoreceptor. This will be tested by (a) continuous simultaneous monitoring of BBF, brain venous pH, ventilation and respiratory muscle EMG; (b) mechanical restriction of BBF; and (c) antagonism of a proposed mediator of the BBF surge, dopamine. (2) It is proposed that during slow wave sleep the BBF response to hypoxia is such that the medulla and its chemoreceptors are preferentially perfused relative to the cortex, as is true in the awake state, but that this differential response is lost in REM sleep and with prolonged hypoxia. This will be tested by serial determinations of regional BBF in the various states using radioactive microspheres. (3) It is proposed that depression of ventilation due to brain hypoxia may be caused by elaboration of two major putative inhibitory neurotransmitters, endogenous opioids and Gamma aminobutyric acid. This will be tested by studies involving selective application of several antagonists and agonists of these agents as well as by measuring brain tissue levels of Gamma aminobutyric acid during brain hypoxia. (4) It is proposed that hypoxic stimulation of the carotid bodies increases the metabolism of ventral medullary respiratory nuclei sufficient to cause stimulation of the central chemoreceptors by their metabolic products, thereby establishing a positive feedback loop in respiratory control. This will be tested by measuring blood flow (uptake of iodoantipyrine) and metabolism (uptake of 2 deoxyglucose) in medullary respiratory nuclei during stimulation of the carotid sinus nerves and by measuring pH at the ventral surface of the medulla during stimulation of the carotid sinus and other sensory nerves.

通气和脑血管对缺氧的反应提供了主要的 针对大脑供氧不足的短期防御 供应在急性和慢性肺病等多种情况下受到威胁 疾病、心血管疾病和爬高海拔。 这些 响应不是自变量，而是与 彼此。 关于脑血流方式的四种假设 和/或脑组织缺氧可能与呼吸控制相互作用 建议的。 (1) 推测脑血流量（BBF）激增 快速眼动睡眠通过减少呼吸神经元输出来减少 PCO2 位于中央化学感受器。 这将通过（a）连续测试 同时监测 BBF、脑静脉 pH 值、通气量和 呼吸肌肌电图； (b) BBF的机械限制；和（三） 所提出的 BBF 激增调节剂多巴胺的拮抗作用。 (2) 是 提出在慢波睡眠期间 BBF 对缺氧的反应是这样的 髓质及其化学感受器优先灌注 相对于皮质，在清醒状态下也是如此，但是这 快速眼动睡眠和长期缺氧会导致差异反应消失。 这将通过不同区域 BBF 的系列测定进行测试。 使用放射性微球的国家。 (3)提出抑郁症 脑缺氧导致的通气障碍可能是由以下两个因素引起的 主要假定的抑制性神经递质、内源性阿片类药物和伽玛 氨基丁酸。 这将通过涉及选择性的研究进行测试 这些药物的几种拮抗剂和激动剂的应用以及 通过测量大脑过程中脑组织中γ-氨基丁酸的水平 缺氧。 (4) 提出对颈动脉体进行缺氧刺激 充分增加腹侧延髓呼吸核的代谢 通过其代谢引起中枢化学感受器的刺激 产品，从而在呼吸系统中建立正反馈循环 控制。 这将通过测量血流量（吸收 碘安替比林）和髓质代谢（2脱氧葡萄糖的摄取） 刺激颈动脉窦神经期间的呼吸核 在刺激过程中测量髓质腹侧表面的 pH 值 颈动脉窦和其他感觉神经。