氧合导向最佳呼气末正压对急性呼吸窘迫综合征犬肺局部气体分布和炎症反应的影响

The effects of positive end-expiratory pressure targeting optimal oxygenation on local gas distribution and inflammation in dogs with acute respiratory distress syndrome

目的 探讨氧合导向最佳呼气末正压（PEEP）对急性呼吸窘迫综合征（ARDS）犬肺组织局部气体分布和炎症反应的影响.方法 静脉注射油酸（油酸组,8只）、肺泡灌洗生理盐水（生理盐水组,8只）复制犬ARDS模型.模型成功后给予氧合导向最佳PEEP进行机械通气,基础状态、模型复制成功及机械通气4 h后均行肺部CT扫描,观察肺局部气体分布.4 h后处死犬,留取肺组织观察病理改变,凝胶迁移率改变电泳（EMSA）测肺组织NF-κB活性,比色法测肺组织髓过氧化物酶（MPO）和丙二醛（MDA）含量,ELISA测肺组织IL-6、IL-10含量.结果 （1）与基础状态比,2组犬模型复制成功后,总肺容积均显著减少,不通气区肺容积明显增加;与模型复制成功时比,2组犬在最佳氧合法确定PEEP水平,CT扫描显示低通气区及不通气区肺容积明显减少,正常通气肺组织增加,但过度膨胀区肺容积也显著增加,以腹侧（非重力依赖区）肺泡过度膨胀明显.与油酸组比,在最佳氧合法确定PEEP水平,生理盐水组过度膨胀区肺容积增多更显著.（2）2组犬肺右下叶腹侧组织损伤评分均明显高于右上叶,肺右下叶背侧组织损伤评分均明显高于右上叶、右下叶腹侧;肺右下叶背侧组织NF-κB活性均明显高于右上叶;肺右下叶背侧、右下叶腹侧组织MPO和MDA含量均明显高于右上叶;肺右下叶背侧组织IL-6、IL-10含量均明显高于右上叶、右下叶腹侧.结论 以氧合导向最佳PEEP致ARDS肺非重力依赖区过度膨胀,加重局部肺损伤.生理盐水组犬肺过度膨胀更显著.

Objective To evaluate the effects of positive end-expiratory pressure （PEEP） targeting optimal oxygenation on local gas distribution and inflammation in dogs with acute respiratory distress syndrome （ARDS）. Methods ARDS was induced by saline alveoli-lavage and oleic acid intravenous. The animals were mechanical ventilated 4 h at optimal PEEP titrated by oxygenation. Computed tomography （CT） scans were performed before and after induction of ARDS and at the end the study. NF-κB was measured by electrophoretic mobility shift assay （EMSA）, IL-6 and IL-10 were assessed by ELISA.Myeloperoxidase （MPO） and malondialdehyde （MDA） were measured. Pathological changes were examined under optical microscope. Results （1） Compared to baseline, total lung volumes decreased and nonaerated areas increased significantly after the induction of ARDS in both groups （P ＜ 0.05 ）. Compared with ARDS models, PEEP titrated to achieve optimal oxygenation resulted in greater lung recruitment but was accompanied with hyperinflation, hyperinflation occurred in non-dependent lung. Compared with oleic acidinjured ARDS, the changing of hyperinflated lung areas was increased markedly in saline lavage-injured ARDS （P＜0.05）. （2） Compared with right lung ventral lower lobe, lung injury score was lower in right lung upper lobe. Histological injury in right lung dorsal lower lobe was severer than that in right lung upper lobe and right lung ventral lower lobe. NF-κB activation of right lung dorsal lower lobe was markedly higher than right lung upper lobe （P ＜ 0.05 ）. MPO and MDA were much higher with right lung dorsal lower lobe than right lung upper lobe and right lung ventral lower lobe （ P ＜ 0.05 ）. Compared with right lung upper lobe and right lung ventral lower lobe, IL-6 and IL-10 increased markedly in right lung dorsal lower lobe （ P ＜ 0.05 ）. Conclusions Alveolar hyperinflation and aggravated lung injury in non-dependent region were occurred at PEEP targeting optimal oxygenation. Hyperinflation was more common in saline lavage-injured ARDS.