Research for protection of pulmonary function during cardiopulmonary bypass

体外循环期间肺功能保护研究

• 批准号: 12671291
• 负责人: ENDO Masato
• 金额: $ 2.11万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671291/
• 关键词: Lung protection; Lung perfusion; Cardiopulmonary bypass; Leukocyte erastase; Leukocyte depletion; IL-6; 顆粒球elastase

Lung perfusion model was made using removed sheep lungs after the initiation of conventional cardiopulmonary bypass (CPB). The lungs were perfused with CPB blood (15 ml/kg/min) and ventilated (FiO2 1.0, 10xboby weight (kg)cc x 15/min). Hemodynamic parameters, respiratory parameters and chemical mediaters were measured at 0, 10, 30, 60 minutes after commencement of lung perfusion. Pulmonary artery pressure and resistance were consistently elevated during lung perfusion. Blood level of leukocyte erastase was also consistently elevated during lung perfusion. Histological examination revealed the persistent edema of alveolar wall and leukocyte accumulation in alveolar space. The area filled with accumulated leukocytes and fibrinoid substance were consistently enlarged during lung perfusion. Pulmonary dysfunction after CPB seemed to be closely related with accumulation of activated leukocytes with active release of cytokines in lung. Leukocyte depletion by leukocyte filter in the line of lung perfusion prevented the elevation of blood leukocyte elastase level. Therefore, leukocyte depletion, leukocyte degranulation inhibitor, leukocyte-endothelial adherence inhibitors are expected to be useful to reduce pulmonary dysfunction during CPB.

采用常规体外循环（CPB）开始后切除的绵羊肺制作肺灌注模型。肺灌注CPB血液（15 ml/kg/min）和通气（FiO 2 1.0，10 x体重（kg）cc x 15/min）。分别于肺灌注开始后0、10、30、60分钟测定血流动力学参数、呼吸参数和化学介质。肺灌注期间肺动脉压力和阻力持续升高。在肺灌注过程中，白细胞erastase的血液水平也持续升高。组织学检查显示肺泡壁持续性水肿，肺泡腔内白细胞聚集。肺灌注过程中白细胞和纤维蛋白样物质聚集区持续扩大。体外循环后肺功能不全与肺内白细胞活化、细胞因子释放活跃密切相关。在肺灌注线中通过白细胞过滤器去除白细胞防止血液白细胞弹性蛋白酶水平升高。因此，白细胞去除剂、白细胞脱颗粒抑制剂、白细胞-内皮细胞粘附抑制剂有望用于减少CPB期间的肺功能障碍。