REGIONAL VENTILATION IN THE NON-UNIFORM LUNG

这项建议的广泛和长期目标是发展更好的 非均匀肺的机械通气策略以及 评估不均匀的肺功能障碍。 这项提议的动机是， 认识到，在呼吸频率的生理范围内， 肺组织的粘弹性对肺动脉高压的发生有重要贡献 阻抗以及弹性和耗散组织力不 独立，但似乎是耦合的， 也倾向于以大致相等的比例影响另一个。 一 这些观察结果的潜在生理意义在于， 在组织中，粘弹性特性可能是控制 局部通气同时保持同步肺扩张， 调制区域弹性而不改变区域时间常数。 这种可能性为早期的推测提供了新的线索， 气道平滑肌收缩可能是体内平衡机制的一部分 以保持V/Q的均匀匹配。 本项目的具体目标是：1）测试一个 非线性模型的平滑肌力学来描述区域 外周血引起的肺组织性质的机械变化 收缩。 2)识别和评估以下生理相关性 肺组织粘弹性的局部变化，以及3）应用这些 概念，以评估肺力学和区域气体运输在非- 统一的系统，特别是由单侧肺 移植 本课题将研究：1）非线性粘弹性 迷走神经刺激期间肺组织的行为及其变化，或 组胺气雾剂 2)局部胸壁-肺相互依赖性。 第三章 肺灌注、PO 2和PCO 2对气道和 组织特性和通气分布。 4)区域变化 单侧肺移植后的肺力学 的共同办法 包括建立简单的力学模型和进行实验 定量评估模型的不同组成部分。 的 方法包括经典的呼吸力学技术，如强制呼吸力学， 振荡和流动中断，以及最近开发的正电子成像 用于动态肺容量的定量区域评估的技术， 气体运输，允许区域肺力学表征为非- 侵入性地 拟议的实验与广泛的非- 统一的呼吸系统疾病，他们特别是有关的 单侧肺移植的管理。 利用 肺移植的同时外科研究，实验已经 旨在定量术后肺功能和局部变化 由于诸如移植排斥、大小不匹配和生长等因素， 和肺保存技术。

The broad, long-term objectives of this proposal are to develop improved strategies for mechanical ventilation of the non-uniform lung and for assessing non-uniform lung dysfunction. This proposal is motivated by the recognition that, in the physiological range of respiratory frequencies, lung tissue visco-elasticity has a major contribution to pulmonary impedance and that elastic and dissipative tissue forces are not independent, but appear to be coupled so that interventions that affect one also tend to affect the other in approximately equal proportion. A potential physiological significance of these observations is that changes in tissue visco-elastic properties could be a major factor in controlling regional ventilation while maintaining synchronous lung expansion by modulating regional elastance without changing regional time constants. This possibility sheds new light on earlier speculations that distal airways smooth muscle constriction could be part of a homeostatic mechanism to maintain uniform matching of V/Q. The Specific Aims of this project are: 1) Test the appropriateness of a non-linear model of smooth muscle mechanics to describe the regional mechanical changes in lung tissue properties caused by peripheral constriction. 2) Identify and assess the physiological relevance of regional changes in lung tissue visco-elasticity and 3) Apply these concepts to evaluate lung mechanics and regional gas transport in a non- uniform system, specifically that resulting from unilateral lung transplant. The project will study: 1) The non-linear visco-elastic behavior of lung tissue and its alteration during vagal stimulation or histamine aerosol. 2) The regional chest wall-lung interdependence. 3) The regional effects of pulmonary perfusion, PO2, and PCO2 on airway and tissue properties and ventilation distribution. 4) The changes in regional lung mechanics after unilateral lung transplantation. The common approach consists of formulating simple mechanical models and performing experiments to quantitatively evaluate the different components of the models. The methods include classical respiratory mechanics techniques, such as forced oscillations and flow interruption, and recently developed positron imaging techniques for quantitative regional assessment of dynamic lung volumes and gas transport, allowing regional lung mechanics to be characterized non- invasively. The proposed experiments are relevant to a broad range of non- uniform respiratory ailments and they are particularly pertinent to the management of the unilaterally transplanted lung. Taking advantage of concurrent surgical research on lung transplantation, experiments have been designed to quantitate postoperative lung function, and regional changes resulting from factors such as graft rejection, size mismatch and growth, and lung preservation techniques.