PROTECTIVE VENTILATORY RESPONSES TO HYPOXIA

对缺氧的保护性通气反应

• 批准号: 6272451
• 负责人: Walter St. John
• 金额: $ 23.27万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6272451
• 关键词: apnea; brain mapping; decerebration; developmental neurobiology; disease /disorder model; hypoxia neonatorum; mesencephalon; newborn animals; pons; pulmonary respiration; respiration regulatory center; sudden infant death syndrome; swine

The protective response to hypoxia is organized in two layers. With initial exposure, eupneic ventilation increase. In severe hypoxia, eupnea is replaced by gasping, which promotes "autoresuscitation." The eupneic ventilatory response to hypoxia changes with development. In the newborn, ventilation rises and then falls. With age, the hypoxia- induced augmentation becomes more sustained. We hypothesize that hypoxia- induced ventilatory depression results from activation of a mesencephalic- pontine "central oxygen detector." Piglets will be studied. We will identify the region containing the "central oxygen detector." Hypoxia-induced depressions of ventilation will be attenuated if neurons of this central oxygen are destroyed. Neuronal activities of this detector will be characterized. These activities are hypothesized to increased during depressions of phrenic activity in hypoxia or during localized hypoxia by applications of sodium cyanide. We will then examine the role of neurons in the ventral medulla in hypoxia-induced ventilatory depressions and in the neurogenesis of gasping. These ventral medullary neuronal activities may provide a generalized tonic input for ventilatory activity. Yet gasping will not be altered since the mechanisms underlying the neurogenesis of eupnea and gasping differ fundamentally. In unanesthetized piglets, ventilatory activity will be recorded during wakefulness and sleep. We hypothesize that apneic episodes will be recorded following ablation of neurons in the medullary gasping center and those in the ventral medulla. Our results will have profound implications as to the mechanisms of apnea and the sudden infant death syndrome. Mechanisms of central apnea may be elucidated by our studies of the "direct" influence of hypoxia on the brainstem ventilatory control system, of the role of ventral medullary mechanisms in this hypoxia-induced depression and the role of medullary gasping mechanisms in the control of eupnea.

对缺氧的保护反应分为两层。和 初次暴露后，呼吸通气量增加。严重缺氧时，呼吸正常 被喘息所取代，从而促进“自动复苏”。 对缺氧的正常通气反应随着发育而变化。在 新生儿，通气量先上升后下降。随着年龄的增长，缺氧 诱导增强变得更加持续。我们假设缺氧 诱发的通气抑制是由中脑神经激活引起的 脑桥“中央氧检测器”。 将对仔猪进行研究。我们将确定包含以下内容的区域： “中央氧气检测仪。”缺氧引起的通气抑制会 如果该中枢氧的神经元被破坏，则该作用会减弱。神经元 该检测器的活动将被表征。这些活动是 假设在膈活动抑制期间增加 缺氧或使用氰化钠造成局部缺氧。 然后我们将检查腹侧延髓中神经元的作用 缺氧引起的通气抑制和神经发生 气喘吁吁。这些腹侧髓质神经元活动可能提供 通气活动的广义强直输入。然而喘气不会 由于安眠神经发生的机制发生了改变 喘气有根本的不同。 在未麻醉的仔猪中，将记录呼吸过程中的通气活动。 清醒和睡眠。我们假设呼吸暂停发作将是 髓质喘息中心神经元消融后记录 那些在腹侧延髓。 我们的结果将对呼吸暂停的机制产生深远的影响 和婴儿猝死综合症。中枢性呼吸暂停的机制可能是 我们的研究阐明了缺氧对身体的“直接”影响 脑干通气控制系统，腹侧延髓的作用 缺氧引起的抑郁症的机制以及延髓的作用 控制真呼吸的喘息机制。