LUNG VAGAL AFFERENTS IN CHRONIC LUNG DISEASE

肺纤维化患者经历了许多功能性的 与肺顺应性降低相关的限制，气体 交换、快速浅呼吸模式与主观感觉 呼吸困难，导致观察到的呼吸的潜在机制 这些患者的模式和呼吸困难反应仍不明确。它 是基于急性研究发现肺迷走神经 传入物质可能会启动或影响这些反应。然而，存在这样的问题， 没有关于这些受体如何应对慢性疾病的信息 从急性研究中得出的条件和推论是 脆弱的。我假设肺组织的炎性成分 纤维化刺激无髓鞘C纤维引起快速浅表 呼吸模式和肺部顺应性的慢性下降 导致慢性刺激有髓迷走神经传入(缓慢 和快速适应肺伸展感受器)，这唤起了缓慢的 浅呼吸模式和频繁的增压呼吸：尖锐 C纤维反应占主导地位，但随着急性炎症的消退 已经解决了。为了检验这些假设，我将进行一系列 进行性痴呆大鼠的反射和神经生理学实验 间质性肺纤维化。这种纤维化将由以下因素引起 反复气管内滴注博莱霉素。测试我的 假设我设计了以下策略。首先，我会 描述以下方面的急性(14天)和慢性(90天)变化 与进行性肺病相关的基线呼吸模式 纤维化，同时测量动脉血气，动脉血压 还有心率。其次，在这两个时间点上，我将确定 肺迷走神经传入神经组(有髓与无髓) 通过以下方式导致肺纤维化引起呼吸模式的改变 神经周围辣椒素首先阻断迷走神经C纤维传导 治疗后C纤维阻滞联合迷走神经冷阻滞术 有髓纤维。第三，我将使用单一神经纤维进行研究 迷走神经传入纤维放电模式的记录技术 并特别强调了它们在实验中对大鼠的反应 诱导进行性肺纤维化。第四，我会在 实验开始时，疾病进程的程度由 测量肺体积和准静态肺顺应性并在结束时 通过摘除肺部并对其进行检查 组织学上。通过更好地了解肺脏 调控机制及其在慢性肺部疾病中的作用 这一领域的研究可能导致更好的治疗方案 患有慢性肺病的个人。

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.