Direct Hemoperfusion with Polymyxin B Immobilized Fiber (PMX) in Acute Lung Injury Induced by Endotoxemia in Anesthetized Sheep

多粘菌素B固定纤维直接血液灌流治疗麻醉羊内毒素血症急性肺损伤

• 批准号: 10672261
• 负责人: HONDA Takayuki
• 金额: $ 0.77万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672261/
• 关键词: Acute lung injury; Acute respiratory distress syndrome; Endotoxemia; anesthetized sheep; Lung lymph fistula; Polymyxin B Immobilized Fiber (PMX); Shock; Respiratory failure; P; F比; PMX-F; エンドトキシン; ガス交換

We have performed the following 2 projects under the grant.(1) In anesthetized sheep with lung lymph fistula and systemic and pulmonary hemodynamic monitoring, we evaluated the effect of direct hemoperfusion with Polymyxin B immobilized fiber (PMX) in acute lung injury (ALI) induced by E. coli endotoxemia (10 μg/kg). Endotoxemia produced shock (decreased systemic blood pressure), pulmonary hypertension, circulating leukopenia and hypoxemia during the early phase after endotoxcmia and the increases in lung lymph flow, suggesting permeability edema, during the late phase. Direct hemoperfusion (60ml/hr) with PMX significantly improved the shock and hypoxemia induced by endotoxemia, though it did not changes the time course of leukopenia, pulmonary hypertension and lung lymph dynamics.(2) We tried to treat 8 patients with ALI and acute respiratory distress syndrome (ARDS) using direct hemoperfusion with PMX. After 2 times of the treatment, systolic systemic pressure (from 105 ± 8 mmHg to 137 ± 5), diastolic pressure (from 63 ± 10 mmHg to 78 ± 7 mmHg) and PaO2/FiO2 (P/F ratio) (from 130 ± 20 to 170 ± 15) were significantly improved.

我们已经完成了以下两个项目的赠款。(1)在麻醉绵羊肺淋巴瘘模型上，通过体、肺血流动力学监测，观察了多粘菌素B固定纤维（PMX）直接血液灌流对E.大肠杆菌内毒素血症（10 μg/kg）。内毒素血症在内毒素血症后的早期阶段产生休克（全身血压降低）、肺动脉高压、循环白细胞减少和低氧血症，在晚期阶段肺淋巴流量增加，提示渗透性水肿。PMX直接血液灌流（60 ml/hr）可明显改善内毒素血症引起的休克和低氧血症，但不改变白细胞减少、肺动脉高压和肺淋巴动力学的时程。(2)我们尝试用PMX直接血液灌流治疗8例ALI和急性呼吸窘迫综合征（ARDS）患者。治疗2次后，收缩压（105 ± 8 mmHg）、舒张压（63 ± 10 mmHg）、PaO 2/FiO 2（P/F比值）（130 ± 20）、舒张压（78 ± 7 mmHg）均明显改善。

项目成果

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Hanaoka 等人：“干扰素-α 会提高绵羊的肺血压 - 血栓素级联的作用。”Eur J Pharmacol. 370. 145-151 (1999)

Honda T, 他: "Type II pneumocytes are preferentially located along thick elastic fibers forming the framework of human alveoli"Anat Rec. 258. 34-38 (2000)

Honda T 等人：“II 型肺细胞优先位于形成人类肺泡框架的厚弹性纤维”Anat Rec. 258. 34-38 (2000)

Hachiya T, 他: "Expression patterns of type II pneumocyte apical surface glycoconjugates in lung adenocarcinoma cells"Virchows Arch. 434. 63-69 (1999)

Hachiya T 等人：“肺腺癌细胞中 II 型肺细胞顶端表面糖缀合物的表达模式”Virchows Arch. 434. 63-69 (1999)

Koizumi et al.: "Lung lymph response to overinfusion with hydroxyethl starch in sheep."Acta Anesthesiol Sandc. (in press).

Koizumi 等人：“绵羊对过度输注羟乙基淀粉的肺淋巴反应。”Acta Anesthesiol Sandc。

Miyahara et al.: "Endothelin receptor blockade attenuates air embolization-induced pulmonary hypertension in sheep."Eur J Pharmacol. 385. 163-169 (1999)

Miyahara 等人：“内皮素受体阻断可减轻绵羊空气栓塞引起的肺动脉高压。”Eur J Pharmacol。