CONTROL OF BREATHING DURING PHYSIOLOGIC CONDITIONS

生理条件下呼吸的控制

• 批准号: 3338215
• 负责人: HUBERT V FORSTER
• 金额: $ 11.14万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-06-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3338215
• 关键词: REM sleep; acid base balance; afferent nerve; anesthesia; apnea; brain metabolism; carbon dioxide; cardiac output; carotid body; cerebrospinal fluid; chemoreceptors; cold injury; denervation; diaphragm; electroencephalography; electromyography; exercise; experimental brain lesion; goats; heart rate; horses; hyperpnea; hypoventilation; medulla oblongata; microinjections; neural plasticity; oxygen transport; phrenic nerve; pulmonary respiration; respiration regulatory center; respiratory hypoxia; respiratory muscles; respiratory oxygen; respiratory reflex; sleep; vagus nerve

The role of the ventrolateral medulla (VLM) and diaphragmatic afferents (DA) in the control of breathing under anesthesia remains controversial, and their role in unanesthetized conditions is even more speculative. Thus our objective is to test controversial hypotheses regarding the VLM and DA during physiologic conditions. For the VLM, we will study awake, anesthetized, and asleep goats using: 1) chronically implanted thermodes to cool (20 degrees) and thereby create reversible neuronal dysfunction at sites near the VLM surface, and 2) microinjections of kainic acid to create permanent neuronal dysfunction at discrete VLM sites. With cooling, dysfunction effects are not obscured by compensatory changes that may occur between studies before and after permanent lesions. With permanent lesions the nuclei underlying functions can be identified. Key hypotheses are: 1) Bilateral dysfunction of an area that includes the retrotrapezoid nucleus (RTN area) will cause apnea or hypoventilation during eucapnia; during several hyperpneic conditions it will not cause apnea but will uniformly attenuate breathing; 2) Bilateral dysfunction more caudally in the intermediate VLM (IVLM) will cause a general attenuation of breathing and respiratory muscle activity, but the attenuation will be greater during elevated CO2-H+ stimulation than during exercise, hypoxia, NaCN infusion, and ventilatory loading; and 3) Simultaneous dysfunction of both the RTN area and the IVLM after carotid chemoreceptor denervation will eliminate the CO2-H+ hyperpnea and cause prolonged apnea in anesthesia and NREM sleep. Testing these hypotheses will suggest whether: 1) the RTN is critical for generation of respiratory rhythm and whether it facilitates more dorsal medullary respiratory neurons, 2) the IVLM integrates or processes intracranial chemoreception and peripheral reflexes, 3) in all states, these VLM sites are critical for CO2-H+ ventilatory sensitivity, and 4) in anesthesia and NREM sleep breathing is critically dependent on the CO2-H+ stimulus and functional RTN and IVLM areas. For DA related objectives, we will study awake ponies. We hypothesize diaphragmatic deafferentation will: 1) reduce the increased stimulation of the diaphragm which occurs in a normal pony as that of reflexes known as operational length compensation and ventilatory load compensation; 2) eliminate this increased stimulation in a lung denervated pony. These findings will support the concept that DA contribute to these reflexes. Our studies will provide unique insights into the control of breathing during physiologic conditions and diseases such as Sudden Infant Death Syndrome, Ondine's Curse, sleep apnea, and COPD.

延髓腹外侧（VLM）和延髓传入的作用 (DA)在麻醉下控制呼吸仍然存在争议， 它们在非麻醉条件下的作用更是推测性的。 因此，我们的目标是测试有争议的假设，关于VLM 生理条件下的DA。 对于VLM，我们将在清醒状态下学习， 麻醉和睡着的山羊，使用：1）长期植入热电偶 冷却（20度），从而产生可逆的神经元功能障碍 在VLM表面附近的位点，和2）微量注射红藻氨酸， 在离散的VLM部位产生永久性神经元功能障碍。 与 冷却、功能障碍效应不会被代偿性变化所掩盖 这可能发生在永久性病变之前和之后的研究之间。 与 永久性损伤，可以识别潜在功能的核团。 关键假设是：1）某个区域的双侧功能障碍，包括 小斜肌后束核（RTN区域）将导致呼吸暂停或 在正常碳酸血症期间通气不足;在几种呼吸过度的情况下， 不会引起呼吸暂停，但会均匀地减弱呼吸; 2） 中间VLM（IVLM）中更尾部的双侧功能障碍将 导致呼吸和呼吸肌的普遍衰减 活性，但在CO2-H+浓度升高时， 刺激比在运动，缺氧，NaCN输注， 3）RTN和RTN同时功能障碍 去颈动脉化学感受器神经支配后， CO_2-H ~+呼吸过度并导致麻醉和NREM中呼吸暂停延长 睡吧 测试这些假设将表明：1）RTN是否 对呼吸节律的产生至关重要， 更多的背侧延髓呼吸神经元，2）IVLM整合或 颅内化学感受和外周反射过程，3）在所有 这些VLM位点对CO2-H+蒸发敏感性至关重要， 4）在麻醉和NREM睡眠中，呼吸严重依赖于 CO2-H+刺激和功能RTN和IVLM区域。 与DA相关 目标，我们将研究清醒的小马。 我们假设， 传入神经阻滞将：1）减少增加的刺激， 横膈膜，发生在正常小马的反射，称为 工作长度补偿和工作负载补偿; 2） 消除这种增加的刺激在肺去神经小马。 这些 研究结果将支持DA有助于这些反射的概念。 我们的研究将为呼吸控制提供独特的见解 在生理条件和疾病，如婴儿猝死 综合征，Ondine的诅咒，睡眠呼吸暂停和COPD。