CONTROL OF BREATHING DURING PHYSIOLOGIC CONDITIONS

生理条件下呼吸的控制

• 批准号: 3338219
• 负责人: HUBERT V FORSTER
• 金额: $ 8.75万
• 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 1991-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3338219
• 关键词: acid base balance; afferent nerve; blood pressure; blood volume; body temperature regulation; brain metabolism; carbon dioxide; cardiac output; carotid body; cerebrospinal fluid; chemoreceptors; denervation; dogs; electroencephalography; electromyography; environmental stressor; erythrocytes; exercise; heart rate; horses; hyperpnea; hypoxia; neural plasticity; norepinephrine; oxygen transport; positive pressure breathing; pulmonary respiration; respiration regulatory center; respiratory gas; respiratory muscles; respiratory oxygen; respiratory reflex; serum; sleep; spinal cord surgery; urine; vagus nerve

Our major objective is to enhance understanding of the control of breathing. A related objective is to gain insight into mechanisms which determine O2 transport during exercise. The 1st specific aim is to determine whether afferents from exercising limbs are critical to the exercise hyperpnea. In pilot studies under anesthesia, the ventilatory (V-E) response to electrically induced exercise was attenuated by lesioning the dorsal lateral sulcus (DLS) & dorsal lateral funiculus (DLF) spinal pathways at the L2 level. Except for the 1st of 4 dogs & the 1st of 2 ponies, lesioning did not compromise ambulation. Accordingly, during treadmill exercise, V-E and blood gases will be studied in 8 awake ponies before and 2-4 weeks after DLS and DLF lesions or sham surgery. A 2nd aim is to determine whether spinal lesioning in carotid body denervated (CBD), hilar nerve denervated (HND), and CBD+HND ponies affects the exercise hyperpnea differently than spinal lesions alone. Studies before and after multiple lesions are a means of testing the hypothesis that multiple mechanisms are capable of mediating the exercise hyperpnea, and therefore the hyperpnea may not be attenuated unless most or all mechanisms are eliminated. A 3rd aim is to test the hypothesis that breathing periodicity at high altitude is due to the increased carotid chemoreceptor gain due to hypoxia combined with the hypocapnia-induced apnea threshold. Breathing, blood gases, and EEG will be monitored in 8 ponies before and after CBD or sham CBD in awake and sleeping states at sea level and during 3 days of hypobaria (PaO2 = 40 mmHg). A 4th aim is to determine whether upper airway, lung, or carotid sensory mechanisms alter respiratory neural output to defend tidal volume when inspiratory muscle length is altered to an unfavorable portion of the length-tension curve. V-E, blood gases, and respiratory muscle EMG will be studied in normal, CBD, HND, and tracheostomized ponies before and during positive pressure breathing (+10CM H2O) which increases lung volume and alters muscle length. A 5th aim is to determine whether the 25% overshoots in heart rate and cardiac output of ponies in the 1st min of work are due to mobilization of splenic erythrocytes or peripheral afferent information. These responses will thus be studied before and after DLS and DLF spinal lesions and in other ponies before and after splenectomy. The pony is a proven model for chronic studies requiring maintenance of physiologic conditions. Accordingly, use of the awake pony provides unique tests of theoretical models and hypotheses developed using other species under conditions of anesthesia.

我们的主要目标是增强对控制的理解 呼吸。 一个相关的目标是深入了解以下机制： 确定运动期间的 O2 输送。 第一个具体目标是 确定来自运动肢体的传入信号对于运动是否至关重要 运动呼吸过度。 在麻醉下的试点研究中，通气 (V-E) 对电诱导运动的反应因损伤而减弱 背外侧沟 (DLS) 和背外侧索 (DLF) L2 级别的通路。 除了 4 只狗中的第一只和 2 只狗中的第一只 小马，损伤并不影响行走。 因此，期间 跑步机运动、V-E 和血气分析将在 8 匹清醒的小马中进行研究 DLS 和 DLF 病变或假手术之前和之后 2-4 周。 第二个目标 是为了确定颈动脉体去神经（CBD）中是否存在脊髓损伤， 肺门神经去神经支配（HND），CBD+HND 小马影响运动 呼吸过度与单独的脊柱病变不同。 研究之前和之后 多个病变是检验多个病变假设的一种手段 机制能够调节运动呼吸过度，因此 呼吸过度可能不会减弱，除非大多数或所有机制都被 被淘汰。 第三个目标是检验呼吸周期性的假设 在高海拔地区是由于颈动脉化学感受器增益增加所致 缺氧与低碳酸血症引起的呼吸暂停阈值相结合。 呼吸， 将在 CBD 或之后对 8 匹小马进行血气分析和脑电图监测 假 CBD 在海平面的清醒和睡眠状态下以及 3 天内 低压（PaO2 = 40 mmHg）。 第四个目标是确定上层是否 气道、肺或颈动脉感觉机制改变呼吸神经输出 当吸气肌长度改变为 长度-张力曲线的不利部分。 V-E、血气和 将在正常、CBD、HND 和 气管切开小马在正压呼吸之前和期间（+10CM H2O）增加肺容量并改变肌肉长度。 第五个目标是 确定心率和心输出量是否超调 25% 小马在工作的第一分钟是由于脾脏的动员 红细胞或外周传入信息。 因此，这些回应将 在 DLS 和 DLF 脊柱损伤之前和之后以及其他小马身上进行研究 脾切除术之前和之后。 小马是慢性病的经过验证的模型 需要维持生理条件的研究。 因此，使用 醒着的小马提供了独特的理论模型测试和 在麻醉条件下使用其他物种提出的假设。