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 短期防御可抵抗大脑的氧气不足 供应在急性和慢性肺部等情况下受到威胁 疾病，心血管疾病和高海拔高度。 这些 响应不是自变量，而是与 彼此。 关于脑血流的方式的四个假设 和/或脑组织缺氧可能与呼吸控制相互作用 建议的。 （1）提议在脑血流（BBF）中涌现 REM睡眠通过减少 中央化学感受器的PCO2。 这将通过（a）连续测试 同时监测BBF，脑静脉pH，通风和 呼吸肌EMG； （b）BBF的机械限制； （c） BBF激增的介体多巴胺的拮抗剂。 （2）是 提议在慢波睡觉期间BBF对缺氧的反应就是这样 延髓及其化学感受器优先灌注 相对于皮层，就像在清醒状态下一样，但是 REM睡眠和长时间缺氧的差异反应失去了差异。 这将通过在各种区域BBF的序列确定来测试 使用放射性微球的状态。 （3）提议抑郁症 由于脑部缺氧而引起的通风可能是由于两个 主要推定的抑制性神经递质，内源性阿片类药物和伽马 氨基丁酸。 这将通过涉及选择性的研究来测试 这些药物的几种对抗者和激动剂的应用以及 通过测量大脑期间γ氨基丁酸的脑组织水平 缺氧。 （4）提出了颈动脉体的低氧刺激 增加腹侧髓质核的代谢足够 通过代谢引起中央化学感受器的刺激 产品，从而在呼吸道中建立正反馈循环 控制。 这将通过测量血流来测试（吸收 iodoantipyrine）和代谢（摄取2种脱氧葡萄糖） 颈动脉窦神经刺激期间的呼吸核和 在刺激期间，测量髓质的腹表面的pH 颈动脉窦和其他感觉神经。