Trittenwein G, Rotta A T, Gunnarsson B, Steinhorn D M
Department of Neonatology and Pediatric Intensive Care Unit, University Children's Hospital, Vienna, Wien, Austria.
Perfusion. 1999 Jan;14(1):49-57. doi: 10.1177/026765919901400108.
Initiation of extracorporeal membrane oxygenation (ECMO) in septic children with severe respiratory failure often improves oxygenation but not pulmonary function. The factors affecting pulmonary function following onset of ECMO are not completely understood, but are thought to involve injury mediated, in part, by reactive oxygen species. We hypothesized that induction of ECMO using 100% oxygen as the sweep gas through the oxygenator would increase lipid peroxidation in endotoxin-primed animals after severe hypoxia. We further speculated that provision of oxygenated blood to the pulmonary circulation via venovenous ECMO would promote a greater degree of oxidative damage to the lung as compared to venoarterial ECMO. Eighteen New Zealand White rabbits were assigned to a control group (control) or two intervention groups subjected to 60 min of venoarterial or venovenous ECMO. ECMO was initiated following an intravenous challenge with 0.5 mg/kg of E. coli endotoxin and a period of global hypoxia leading to an arterial pH of 6.99 +/- 0.09, PaCO2 of 103 +/- 31 mmHg and PaO2 of 27 +/- 5 mmHg. Malondialdehyde (MDA), a marker of lipid peroxidation, was measured in lung tissue homogenates and in arterial plasma. Lung tissue MDA demonstrated a strong trend towards an increase in the venoarterial group (1884 +/- 945 nmol/g protein) and in the venovenous group (1905 +/- 758 nmol/g protein) in comparison to the control group (644 +/- 71 nmol/g protein) (p = 0.1; significance at 95% in Scheffe test). Lung tissue MDA in the venovenous group had a significant correlation with mean PaO2 during ECMO by regression analysis (r2 = 0.678, p = 0.044). The change in blood MDA concentration between pre-ECMO and post-ECMO values was greater in the venovenous group (pre 1.62 +/- 0.61 versus post 5.12 +/- 0.2.07 mumol/l, p = 0.043) compared with that seen in the venoarterial group (pre 1.46 +/- 0.38 versus post 3.9 +/- 0.93 mumol/l). Our data support the hypothesis that initiation of ECMO with a circuit gas oxygen concentration of 100% after global hypoxia enhances oxidative damage to lipids in endotoxin-challenged animals. During venovenous ECMO this finding is dependent on PaO2.
在患有严重呼吸衰竭的脓毒症儿童中启动体外膜肺氧合（ECMO）通常可改善氧合，但对肺功能无改善作用。ECMO启动后影响肺功能的因素尚未完全明确，但认为部分涉及活性氧介导的损伤。我们假设，在严重缺氧后，使用100%氧气作为通过氧合器的吹扫气来启动ECMO会增加内毒素预处理动物的脂质过氧化。我们进一步推测，与静脉-动脉ECMO相比，通过静脉-静脉ECMO向肺循环提供氧合血会对肺造成更大程度的氧化损伤。将18只新西兰白兔分为对照组（control）或两个干预组，分别接受60分钟的静脉-动脉或静脉-静脉ECMO。在静脉注射0.5mg/kg大肠杆菌内毒素并经历导致动脉pH值为6.99±0.09、动脉血二氧化碳分压（PaCO2）为103±31mmHg和动脉血氧分压（PaO2）为27±5mmHg的全身性缺氧后启动ECMO。在肺组织匀浆和动脉血浆中测量脂质过氧化标志物丙二醛（MDA）。与对照组（644±71nmol/g蛋白质）相比，静脉-动脉组（1884±945nmol/g蛋白质）和静脉-静脉组（1905±758nmol/g蛋白质）的肺组织MDA呈现出明显的升高趋势（p = 0.1；在Scheffe检验中95%水平具有显著性）。通过回归分析，静脉-静脉组的肺组织MDA与ECMO期间的平均PaO2显著相关（r2 = 0.678，p = 0.044）。与静脉-动脉组（ECMO前1.46±0.38 versus ECMO后3.9±0.93μmol/l）相比，静脉-静脉组ECMO前后血MDA浓度变化更大（ECMO前1.62±0.61 versus ECMO后5.12±2.07μmol/l，p = 0.043）。我们的数据支持以下假设：在全身性缺氧后以100%的回路气体氧浓度启动ECMO会增强对内毒素攻击动物脂质的氧化损伤。在静脉-静脉ECMO期间，这一发现取决于PaO2。
