Rinaldo J E, English D, Levine J, Stiller R, Henson J
Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Am Rev Respir Dis. 1988 Feb;137(2):345-52. doi: 10.1164/ajrccm/137.2.345.
Sequential lung injuries, such as oxygen toxicity followed by septicemia, are common during the adult respiratory distress syndrome (ARDS). As these forms of vascular injury may be mediated in part by polymorphonuclear leukocytes (PMN), aberrant interactions between PMN and previously injured pulmonary endothelium are of both theoretical interest and clinical importance. The present study was undertaken to test the hypothesis that early oxygen toxicity at a dose that injuries pulmonary endothelium relatively selectively alters intrapulmonary neutrophil kinetics. Unanesthetized rats breathing 1.0 atmospheres oxygen for 36 h showed ultrastructural endothelial damage but no edema, injury, or neutrophilic inflammation by histologic criteria. However, in these oxygen-toxic animals, whereas initial accumulation of radiolabeled PMN in lungs was normal, washout of PMN was abnormal at 120 min after infusion, at which point the pulmonary retention of radiolabeled PMN in the lungs of oxygen-treated animals was significantly higher than in control animals (139% of control, p less than 0.0096). Features of our methodology, including avoidance of osmotic stress and use of paired control animals, appear to have greatly enhanced the sensitivity of radiolabeled neutrophils for detecting a subtle abnormality of neutrophil-endothelial interactions. Our studies in the oxygen toxicity model provide the first demonstration in vivo of abnormal intrapulmonary neutrophil kinetics in early oxygen toxicity prior to the onset of histologic evidence of lung injury or inflammation.
在成人呼吸窘迫综合征（ARDS）期间，序贯性肺损伤很常见，例如氧中毒后继发败血症。由于这些血管损伤形式可能部分由多形核白细胞（PMN）介导，因此PMN与先前受损的肺内皮之间异常相互作用在理论上具有重要意义，在临床上也很重要。本研究旨在验证以下假设：相对选择性损伤肺内皮的剂量的早期氧中毒会改变肺内中性粒细胞动力学。未麻醉的大鼠呼吸1.0个大气压的氧气36小时，通过组织学标准显示有超微结构的内皮损伤，但无水肿、损伤或中性粒细胞炎症。然而，在这些氧中毒动物中，虽然放射性标记的PMN在肺中的初始蓄积正常，但在输注后120分钟时PMN的清除异常，此时经氧处理动物肺中放射性标记的PMN的肺内滞留量显著高于对照动物（为对照的139%，p<0.0096）。我们方法的特点，包括避免渗透应激和使用配对对照动物，似乎大大提高了放射性标记中性粒细胞检测中性粒细胞与内皮相互作用细微异常的敏感性。我们在氧中毒模型中的研究首次在体内证明了在肺损伤或炎症的组织学证据出现之前，早期氧中毒时肺内中性粒细胞动力学异常。
