OXYGEN TOXICITY AND PULMONARY VASCULAR INJURY

我们最近发现了氧中毒对肺的新影响， （i）高氧（急性、适应性和亚急性）期间的血管，和 额外损伤;（ii）撤机到空气中;（iii）在空气中恢复。 我们将 实验研究在大鼠这些血管损伤在正常 肺和肺内进行性纤维化。 形态测量技术， 通过光学和电子显微镜，将建立时间过程， 腺泡前和腺泡内肺动脉损伤的严重程度， 包括闭塞的血管和壁重建的专利。 这些发现将与疾病的发展、严重程度和 通过使用留置针确定的肺动脉高压持续存在 导尿管 我们将测试以下假设：高氧诱导的 结构变化和肺动脉高压密切相关， 重建的肺血管床感觉到减少但仍然高氧 紧张，缺氧和收缩，逐渐断奶改变， 对这一点的敏感性;重建床的响应， 血管收缩剂将增加，血管扩张剂减少;在 高氧引起的纤维化肺肺血管损伤发生得更快， 较低的张力，而回归将更慢，更不完全，因为 通畅血管和大管腔中持续性外膜纤维化 毁灭 细胞对高氧损伤的适应是 在血管壁的非肌肉区域的肌肉，有助于 通过缩小未闭节段并可能改变 血管活性 我们将探讨"前体平滑肌 远端动脉段非肌性区域内膜内的细胞 通过表型的改变发育成新的中膜肌细胞。 建立 我们将通过放射自显影术检查细胞的增殖反应， 用免疫细胞化学方法观察肺动脉壁的损伤 平滑肌肌球蛋白的合成技术。 我们将把 亚细胞有丝分裂和肌球蛋白合成的模式和时间 前体细胞（微丝、致密体和细胞）的特征 位置与基底膜和内弹性膜相关）， 这与成熟中膜平滑肌细胞数量的增加有关。

We have recently identified new effects of oxygen toxicity on pulmonary blood vessels (i) during hyperoxia (acute, adaptive and subacute), and additional injury; (ii) weaning to air and (iii) recovery in air. We will study experimentally in the rat these blood vessel injuries in the normal lung and in the lung with progressive fibrosis. Morphometric techniques, with light and electron microscopy, will establish the temporal course and severity of pulmonary artery damage in preacinar and intraacinar segments, including obliteration of vessels and wall restructuring of patent ones. These findings will be correlated with the development, severity and persistence of pulmonary hypertension established by the use of indwelling catheters. We will test the following hypotheses: that hyperoxia-induced structural changes and pulmonary hypertension correlate closely, that the restructured pulmonary vascular bed senses a reduced but still hyperoxic tension as hypoxia and constricts, and that gradual weaning alters sensitivity to this; that the response of the restructured bed to a vasoconstrictor will increase and to a vasodilator decrease; that in the fibrotic lung pulmonary vascular injury by hyperoxia occurs faster and at a lower tension while regression will be slower and less complete because of persistent adventitial fibrosis in patent vessels and greater lumen obliteration. A cellular adaptation to hyperoxic injury is the development of muscle in non-muscular regions of the vessel wall, contributing to hypertension by narrowing patent segments and perhaps modifying vasoactivity. We will explore the hypothesis that 'precursor smooth muscle cells' within the intima of non-muscular regions of distal artery segments develop into new medial muscle cells by change in phenotype. To establish this we will examine by autoradiography the proliferative response of cells of the pulmonary artery wall to hyperoxic injury and by immunocytochemical techniques the synthesis of smooth muscle myosin. We will corrrelate the pattern and timing of mitosis and myosin synthesis with subcellular features of the precursor cells (microfilaments, dense bodies and cell position in relation to basement membrane and internal elastic lamina) and relate this to increase in number of mature medial smooth muscle cells.