LUNG VAGAL AFFERENTS IN CHRONIC LUNG DISEASE

肺纤维化患者经历许多功能性 与肺顺应性降低、气体 交换，浅快呼吸模式和主观感觉 呼吸困难，导致观察到的呼吸的潜在机制 在这些患者中的模式和呼吸困难反应仍不明确。它 根据急性研究的发现，肺迷走神经 传入神经可以启动或影响这些反应。然而， 没有关于这些受体如何对慢性 条件，因此从急性研究中得出的推论是 脆弱我假设肺部的炎症成分 纤维化刺激无髓鞘C纤维， 呼吸模式和肺顺应性的慢性下降 导致有髓鞘迷走神经传入神经的慢性刺激（缓慢地 和快速适应的肺牵张感受器）， 浅呼吸模式与频繁的呼吸增强：急性 C纤维反应占主导地位，但随着急性炎症的消退， 解决了为了验证这些假设，我将进行一系列的 进行性脑缺血大鼠的反射和神经生理学实验 间质性肺纤维化这种纤维化是由 反复气管内滴注博来霉素。测试我 假设我设计了以下策略。首先我会 表征急性（14天）和慢性（90天）变化， 与进行性肺动脉高压相关的基线呼吸模式 纤维化，同时测量动脉血气、动脉血压 和心率第二，在这两个时间点，我将确定 肺迷走神经传入纤维组（有髓与无髓） 有助于纤维化引起的呼吸模式的改变， 辣椒素神经周阻滞迷走神经C纤维传导 C纤维阻滞结合迷走神经冷阻滞 有髓纤维第三，我将使用单个神经纤维进行研究 迷走神经传入纤维的放电模式 并特别强调了它们在实验性大鼠中的反应 导致进行性肺纤维化。第四，我将在 在实验开始时， 测量肺容量和准静态肺顺应性， 通过取出肺并检查它们 组织学上。通过更好地了解肺部 调节机制及其在慢性肺病中的作用 这一领域的研究可能会导致更好的治疗方案， 患有慢性肺病的人。

Patients with pulmonary fibrosis experience numerous functional limitations which are associated with a decreased lung compliance, gas exchange, rapid shallow breathing pattern and the subjective sensation of dyspnea, The underlying mechanisms leading to the observed breathing pattern and dyspnea response in these patients remains undefined. It has been suggested based on findings from acute studies that lung vagal afferents may initiate or influence these responses. There is, however, no information relating how these receptors respond to chronic conditions and therefore inferences drawn from acute studies are tenuous. I hypothesize that the inflammatory components of pulmonary fibrosis excite nonmyelinated C fibers to evoke a rapid shallow breathing pattern and that a chronic decrease in lung compliance results in a chronic stimulation of myelinated vagal afferents (slowly and rapidly adapting pulmonary stretch receptors) that evoke a slow shallow breathing pattern with frequent augmented breaths: acutely the C fiber response predominates but regresses as the acute inflammation is resolved. To test these hypotheses I will undertake a series of reflex and neurophysiological experiments in rats with progressive interstitial pulmonary fibrosis. This fibrosis will be induced by the repeated intratracheal instillations of bleomycin. To test my hypotheses I have devised the following strategy. First, I will characterize the acute (14 days) and chronic (90 days) alterations in baseline breathing pattern associated with progressive pulmonary fibrosis, while measuring arterial blood gases, arterial blood pressure and heart rate. Second, at these two time points I will determine which group of lung vagal afferents (myelinated versus nonmyelinated) contributes to fibrosis evoked alterations in breathing pattern by first blocking vagal C fiber conduction with perineural capsaicin treatment and then combining the C fiber block with cold block of vagal myelinated fibers. Third, I will investigate using single nerve fiber recording techniques the discharge pattern of vagal afferent fibers with special emphasis on how they respond in rats with experimentally induced progressive pulmonary fibrosis. Fourth, I will examine at the beginning of the experiment the extent of the disease process by measuring lung volumes and quasi-static lung compliance and at the end of the experiment by removing the lungs and examining them histologically. By providing a better understanding of pulmonary regulatory mechanisms and the role they play in chronic lung disease this area of investigation could lead to better treatment protocols for individuals suffering from chronic lung disease.