Meyrick B, Brigham K L
Lab Invest. 1983 Apr;48(4):458-70.
Infusion of Escherichia coli endotoxin into sheep causes a syndrome analogous to the adult respiratory distress syndrome. Physiologic measurements show an initial phase of marked pulmonary hypertension followed by a phase characterized by the production of large quantities of protein-rich lung lymph. The present study relates the structural changes that occur during endotoxemia to concomitant functional changes. In five anesthetized open-chest sheep, we monitored pulmonary and systemic artery pressure for a 1 hour baseline period and for 4 hours after the start of E. coli endotoxin infusion (1.25 microgram/kg, intravenously). We also measured cardiac output, arterial blood gases and pH, and number of circulating leukocytes. In addition, we sequentially biopsied random lobes from the lungs of each sheep at baseline and at 15, 30, 60, 120, 180, and 240 minutes after the start of endotoxin. Five control sheep were treated identically except that they received saline instead of endotoxin. By 15 minutes after the start of endotoxin infusion, light microscopy revealed margination and accumulation of leukocytes in the lungs' microcirculation. Counts of the number of peripheral lung granulocytes in biopsy specimens showed a 3-fold increase above baseline by 15 minutes and a 6-fold increase by 4 hours. By electron microscopy, the leukocytes were identified as both granulocytes and lymphocytes, present in approximately equal numbers. Some granulocytes were fragmented, and specific granules were found free in the vessel lumen. By 30 minutes, some leukocytes were migrating into the interstitium. By 60 minutes, interstitial edema was seen, and there was focal endothelial cell damage. Correlation of the structural with the physiologic changes shows that the initial accumulation of leukocytes in the microcirculation occurs when pulmonary hypertension develops. The migration of leukocytes into the interstitium and endothelial cell damage precedes the physiologic changes that we interpret as increased pulmonary vascular permeability. Since gram negative septicemia is a frequent occurrence in the adult respiratory distress syndrome the changes described here may be similar to the alterations that occur early in the development of the syndrome in man.
给绵羊输注大肠杆菌内毒素会引发一种类似于成人呼吸窘迫综合征的综合征。生理学测量显示，最初阶段会出现明显的肺动脉高压，随后阶段的特征是产生大量富含蛋白质的肺淋巴液。本研究将内毒素血症期间发生的结构变化与伴随的功能变化联系起来。在五只麻醉开胸的绵羊中，我们在1小时的基线期以及开始输注大肠杆菌内毒素（1.25微克/千克，静脉注射）后的4小时内监测肺动脉和体动脉压力。我们还测量了心输出量、动脉血气和pH值以及循环白细胞数量。此外，我们在基线时以及内毒素开始输注后的15、30、60、120、180和240分钟，依次从每只绵羊的肺中随机取叶进行活检。五只对照绵羊接受相同的处理，只是它们输注的是生理盐水而非内毒素。在内毒素输注开始后15分钟，光学显微镜显示白细胞在肺微循环中出现边缘化和聚集。活检标本中肺外周粒细胞计数显示，到15分钟时比基线增加了3倍，到4小时时增加了6倍。通过电子显微镜观察，白细胞被鉴定为粒细胞和淋巴细胞，数量大致相等。一些粒细胞破碎，在血管腔内发现有游离的特异性颗粒。到30分钟时，一些白细胞迁移到间质中。到60分钟时，可见间质水肿，并有局灶性内皮细胞损伤。结构变化与生理变化的相关性表明，白细胞在微循环中的最初积聚发生在肺动脉高压发展之时。白细胞迁移到间质和内皮细胞损伤先于我们认为是肺血管通透性增加的生理变化。由于革兰氏阴性败血症在成人呼吸窘迫综合征中经常发生，这里描述的变化可能与人该综合征早期发展过程中发生的改变相似。
