LIMITATION TO EXERCISE AFTER PNEUMONECTOMY

肺切除术后限制运动

• 批准号: 2219482
• 负责人: ROBERT LEE JOHNSON
• 金额: $ 29.83万
• 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/2219482
• 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.

脊髓灰质炎切除术（PNX）为研究脊髓灰质炎提供了一个强有力的实验工具， 对肺泡上皮细胞可量化损失的代偿反应机制 毛细血管表面积，增加通风的功率要求， 心脏和呼吸泵的不对称扭曲， 已知血管床丧失导致的肺血管阻力。 其机制包括毛细血管储备的募集，肺的生长， 心脏和呼吸肌肥大。 相对重要性和 这些机制的局限性尚不清楚。 在成年犬中，肺切除术后代偿的性质和程度是 取决于切除的范围;相对补偿更多 切除后58%较切除后42%有活力。 肺泡生长是 58%切除后刺激，42%切除后不刺激。 代偿性肺泡 生长不伴随气道生长;气道阻力和 在离开或离开后， 右肺切除术 横膈膜的解剖学变形， 肋间肌可能进一步导致呼吸紊乱， 肌肉力学 我们的目标是确定限制和机制 犬广泛肺损伤后的功能损害和代偿 切除术 我们提出以下问题：1）解释性限制 显著有助于减少最大O2摄取后， 肺切除术2)结构和功能的限制是什么 补偿？ 我们的假设是代偿性肺泡生长 在切除68%后将更加活跃，但最终功能 容量将小于42%或58%切除后，因为 由于更广泛的气道丧失导致更大的呼吸障碍 横截面积，不存在代偿性气道生长，和/或 呼吸泵的解剖学变形 回答问题1 最大O2摄取量将在无外部负荷、有外部负荷的情况下测量。 增加呼吸功2至3倍的负荷， 通过呼吸氦氧混合物来卸荷 静态和动态测量 将测量肺和胸腔顺应性和阻力， 呼吸总功的估计。 呼吸肌血流量 运动期间的需求将由荧光 微球技术同时测量通气量和 解释力。 为了解决问题2，二期肺切除术将 进行，通过不平衡切除（右）切除68%的肺 PNX+左上叶切除术）导致纵隔移位和解剖学 横膈膜和肋间肌肉的扭曲，或通过平衡 切除术（每侧双叶切除术），每侧保留相等的肺体积 半侧胸廓不伴纵隔移位和胸廓不对称变形 呼吸肌 这些组的比较检查了 在固定的扩张水平下解剖呼吸肌扭曲， 剩下的肺。 将从功能上研究补偿机制 在清醒的狗在休息和运动，并在结构上安乐死后， 肺和呼吸肌的形态测定。