REGIONAL VENTILATION IN THE NON-UNIFORM LUNG

这项提案的广泛、长期目标是开发改进的 非均匀肺的机械通气策略及治疗 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， 肺组织粘弹性在肺损伤中的重要作用 阻抗以及弹性和耗散组织力不是 独立的，但似乎是耦合的，所以影响一个人的干预 也倾向于以大致相等的比例影响其他人。一个 这些观察的潜在生理学意义在于， 在组织中，粘弹性特性可能是控制 区域通风，同时通过以下方式保持同步肺扩张 在不改变区域时间常数的情况下调节区域弹性。 这种可能性为早先的猜测提供了新的线索，即远端 气道平滑肌收缩可能是体内平衡机制的一部分 保持V/Q的统一匹配。 该项目的具体目标是：1)测试 用非线性模型描述局部的平滑肌力学 外周因素对肺组织力学性质的影响 收缩。2)确定和评估以下各项的生理相关性 肺组织粘弹性的区域性变化和3)应用这些 评估非沙尘暴的肺力学和区域气体输送的概念 统一系统，特别是由单侧肺引起的系统 移植。本课题将研究：1)非线性粘弹性 迷走神经刺激时肺组织的行为及其变化 组胺气雾剂。2)区域胸壁与肺的相互依存关系。3) 肺血流灌注、氧分压和二氧化碳分压对气道和肺功能的影响 组织特性和通风分布。4)地区性的变化 单侧肺移植后的肺力学研究。共同的方法 包括建立简单的力学模型和进行实验 对模型的不同组成部分进行定量评价。这个 方法包括经典的呼吸力学技术，如强迫 振荡和流动中断，以及最近发展的正电子成像 动态肺活量的定量区域评估技术和 气体运输，允许区域性肺力学被描述为非 侵犯性的。拟议的实验涉及范围广泛的非 统一的呼吸道疾病，它们特别与 单侧肺移植的处理。利用 肺移植的同期外科研究，实验已经完成 旨在量化术后肺功能和局部变化 由移植排斥、大小不匹配和生长等因素造成， 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.