Tillman B F, Loyd J E, Malcolm A W, Holm B A, Brigham K L
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J Appl Physiol (1985). 1989 Mar;66(3):1273-9. doi: 10.1152/jappl.1989.66.3.1273.
Radiation pneumonitis is a life-threatening result of therapeutic thoracic irradiation, yet its mechanisms are poorly understood. We studied the effects of unilateral lung irradiation (3,000 rad) in sheep from the immediate response to the later development of radiation pneumonitis. We defined radiation pneumonitis by its diagnostic clinical feature, radiographic infiltration of the irradiated zone with a straight margin corresponding to the radiation port. The immediate response in the few hours after irradiation was characterized by cough, labored respiration, hypoxemia (arterial PO2 decreased 19 Torr), mild pulmonary hypertension (pulmonary arterial pressure increased 20%), and lymphopenia. Hemodynamics and gas exchange returned to normal by day 2 but became abnormal again before or during radiation pneumonitis at 32 +/- 2 days. Respiratory distress, hypoxemia, and pulmonary hypertension recurred during radiation pneumonitis. Bronchoalveolar lavage during radiation pneumonitis contained increased neutrophils (19 +/- 4%, control = 7%), increased protein (0.27 +/- 0.1 g/dl, control = 0.12 +/- 0.03), and severely impaired ability to lower surface tension. Alveolar macrophages from both lungs during unilateral radiation pneumonitis exhibited impaired generation of superoxide after phorbol myristate (only a 30% increase). Normal control alveolar macrophages increased superoxide production after stimulation greater than 400%. We conclude that unilateral lung irradiation in sheep causes a mild immediate response followed by radiation pneumonitis at 1 mo. Unilateral radiation pneumonitis in this model is associated with ipsilateral neutrophilic alveolitis, increased bronchoalveolar lavage protein, and impaired surfactant function, as well as bilateral functional abnormalities of alveolar macrophages.
放射性肺炎是胸部放疗危及生命的后果，但其发病机制尚不清楚。我们研究了绵羊单侧肺照射（3000拉德）后从即时反应到放射性肺炎后期发展的影响。我们根据其诊断性临床特征来定义放射性肺炎，即照射区域出现具有与放射野相对应的直边的影像学浸润。照射后数小时的即时反应表现为咳嗽、呼吸费力、低氧血症（动脉血氧分压降低19托）、轻度肺动脉高压（肺动脉压升高20%）和淋巴细胞减少。血流动力学和气体交换在第2天恢复正常，但在32±2天放射性肺炎发生前或期间再次变得异常。放射性肺炎期间再次出现呼吸窘迫、低氧血症和肺动脉高压。放射性肺炎期间支气管肺泡灌洗显示中性粒细胞增多（19±4%，对照组为7%）、蛋白质增加（0.27±0.1克/分升，对照组为0.12±0.03），以及降低表面张力的能力严重受损。单侧放射性肺炎期间，来自两侧肺的肺泡巨噬细胞在佛波酯肉豆蔻酸酯刺激后超氧化物生成受损（仅增加30%）。正常对照肺泡巨噬细胞在刺激后超氧化物产量增加超过400%。我们得出结论，绵羊单侧肺照射会引起轻度即时反应，随后在1个月时发生放射性肺炎。该模型中的单侧放射性肺炎与同侧中性粒细胞性肺泡炎、支气管肺泡灌洗蛋白增加、表面活性物质功能受损以及肺泡巨噬细胞的双侧功能异常有关。
