NHLBI CLINICAL INVESTIGATOR AWARD PROGRAM

拟议研究的目标是表征生理和 肺血管的代谢改变，以及这些机制 改变，肺损伤后导致通透性增加 肺水肿 α-萘基硫脲，高氧， 辐射，羟基自由基和野百合碱将进行研究。 他们的 对血管张力和升压反应性调节的影响 刺激，以及肺循环的代谢功能， 将使用离体灌注的大鼠肺进行比较。 的可能性 介质释放的改变可以解释观察到的细胞内 将使用介质抑制剂评估血管张力的调节 潜在介质浓度的研究和系列测量。 为了确定是否由急性炎症引起的生理和代谢改变， 面对反复或长时间的损伤，我们计划 在一定的损伤后进行长期实验。 这些 实验将涉及肺血流动力学测量在完整的 动物，以及一系列的生理和代谢研究， 孤立的肺 因为内皮细胞的损伤可能是 在肺循环对肺损伤的反应中的作用，我们还 计划将在完整肺中观察到的损伤反应与 培养的内皮细胞的反应。 我们的目标是提高 了解肺血管对肺损伤的反应 类似于成人呼吸窘迫综合征，从而提供 改善临床管理的线索。

The goal of the proposed research is to characterize physiologic and metabolic alterations of lung vasculature, as well as mechanisms of those alterations, following lung injury resulting in increased permeability pulmonary edema. Injuries to lung by alpha-naphthylthiorea, hyperoxia, radiation, hydroxyl radicals and monocrotaline will be studied. Their effects on the regulation of vascular tone and responsiveness to pressor stimuli, as well as on metabolic functions of the pulmonary circulation, will be compared using isolated, perfused rat lungs. The possibility that alterations in mediator release could account for observed changes in the regulation of vascular tone will be assessed using mediator inhibitor studies and serial measurements of concentrations of potential mediators. To determine whether physiologic and metabolic alterations caused by acute lung injury persist in the face of repeated or prolonged injury, we plan to conduct long-term experiments following certain injuries. These experiments will involve pulmonary hemodynamic measurements in intact animals, as well as serial physiologic and metabolic studies on their isolated lungs. Because injury to the endothelial cell may play a central role in the response of the pulmonary circulation to lung injury, we also plan to correlate responses to injury observed in the intact lung with responses of endothelial cells in culture. Our aim is to improve understanding of responses of the lung vasculature to lung injuries resembling the Adult Respiratory Distress Syndrome, and thereby provide clues to improved clinical management.