LIMITATION TO EXERCISE AFTER PNEUMONECTOMY

肺切除术后限制运动

• 批准号: 2714007
• 负责人: ROBERT LEE JOHNSON
• 金额: $ 32.5万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2714007
• 关键词: aerobic exercise; diaphragm; dogs; hemodynamics; lung alveolus; oxygen consumption; pneumonectomy; respiratory airway volume; respiratory circulation; respiratory muscles; respiratory oxygenation; thorax

Pneumonectomy (PNX) provides a powerful experimental tool for studying mechanisms of compensatory response to quantifiable losses of alveolar capillary surface area, increased power requirements of ventilation, asymmetrical distortions of the heart and respiratory pumps, and increased pulmonary vascular resistance from a known loss of vascular bed. Mechanisms include recruitment of capillary reserves, lung growth, hypertrophy of heart and respiratory muscles. Relative importance and limits of these mechanisms are unclear. In adult dogs the nature and extent of compensation after pneumonectomy is dependent on the extent of resection; relative compensation is more vigorous after 58% resection than after 42%. Alveolar lung growth is stimulated after 58% resection but not after 42%. Compensatory alveolar growth is not accompanied by airway growth; airway resistance and ventilatory power requirements remain significantly elevated after left or right pneumonectomy. Anatomical distortion of the diaphragm and intercostal muscles may further contribute to derangement of respiratory muscle mechanics. Our objectives are to define the limits and mechanisms of functional impairment and compensation in dogs after extensive lung resection. We ask the following questions: 1) Do ventilatory limitations significantly contribute to the reduced maximal O2 uptake after pneumonectomy? 2) What are the limits of structural and functional compensation? Our hypothesis is that compensatory alveolar lung growth will be even more vigorous after 68% resection but ultimate functional capacity will be less than after either 42 or 58% resection because of greater ventilatory impairment owing to more extensive loss of airway cross-sectional area, the absence of compensatory airway growth, and/or anatomical distortion of the respiratory pump. To address Question 1 maximal O2 uptake will be measured with no external load, with external loads that increase work of breathing 2 to 3 fold and with the system unloaded by breathing a He-O2 mixture. Static and dynamic measurements of lung and thoracic compliance and resistance will be measured to provide estimates of total work of breathing. Respiratory muscle blood flow requirements during exercise will be determined by the fluorescent microsphere technique simultaneously with measurements of ventilation and ventilatory power. To address Question 2, two-stage lung resections will be performed, removing 68% of lung either by unbalanced resection (right PNX+left upper lobectomy) resulting in mediastinal shift and anatomical distortion of the diaphragm and intercostal muscles, or by balanced resection (bilobectomy on each side) leaving equal lung volumes in each hemithorax without mediastinal shift and asymmetrical distortion of respiratory muscles. Comparison of these groups examines the effects of anatomical respiratory muscle distortion at a fixed level of expansion of the remaining lung. Compensatory mechanisms will be studied functionally in the awake dog at rest and exercise and structurally after euthanasia by morphometry of both the lung and respiratory muscles.

肺部切除术（PNX）提供了一种强大的实验工具 对可量化牙槽损失的补偿性响应机制 毛细血管表面积，通风的功率要求增加， 心脏和呼吸泵的不对称扭曲，并增加 已知血管床丧失的肺血管阻力。 机制包括募集毛细管储量，肺部生长， 心脏和呼吸肌肉的肥大。 相对重要性和 这些机制的限制尚不清楚。 在成年狗中，肺切除术后的赔偿性质和程度为 取决于切除程度；相对补偿更多 切除58％后比42％之后蓬勃发展。 肺泡肺的生长是 切除58％后刺激，但在42％后不进行。 补偿性肺泡 增长不伴有气道增长；气道阻力和 左后或 右肺切除术。 diaphragm和 肋间肌肉可能进一步导致呼吸道危害 肌肉力学。 我们的目标是定义限制和机制 大量肺后狗的功能障碍和补偿 切除。 我们提出以下问题：1）进行通风限制 显着导致最大O2的最大摄取 肺切除术？ 2）结构和功能的限制是什么 赔偿？ 我们的假设是补偿性肺泡肺的生长 68％切除后将更加有活力，但最终功能 由于有42％或58％的切除后，容量将少于 由于气道的广泛损失，更大的通气障碍 横截面区域，缺乏补偿性气道增长和/或 呼吸泵的解剖变形。 解决问题1 最大O2吸收将在没有外部负载的情况下测量，外部 增加呼吸工作2至3倍的负载，并随着系统而 通过呼吸He-O2混合物卸载。 静态和动态测量 将测量肺和胸腔依从性和阻力以提供 总呼吸工作的估计。 呼吸肌血流动 运动过程中的要求将由荧光确定 微球技术与通风和通风的测量和 通风能力。 为了解决问题2，两个阶段的肺切除术将 可以执行，通过不平衡切除去除68％的肺（右） PNX+左上叶切除术）导致纵隔转移和解剖学 隔膜和肋间肌肉的变形，或平衡 切除（每侧的双向切除术）在每种 不具有纵隔移位和不对称失真的半胸 呼吸肌。 这些组的比较检查了 在固定水平的扩张水平的解剖学呼吸肌失真 其余的肺。 补偿机制将在功能上研究 在休息时清醒的狗中，在安乐死之后进行运动和结构 肺和呼吸肌的形态计量学。