Fujii Yutaka, Tatsumi Eisuke, Nakamura Fujio, Oite Takashi
Department of Clinical Engineering and Medical Technology, Niigata University of Health and Welfare, Niigata, Japan.
Department of Artificial Organs, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.
J Thorac Dis. 2020 Mar;12(3):749-757. doi: 10.21037/jtd.2019.12.113.
Extracorporeal membrane oxygenation (ECMO) is being increasingly used for mechanical support of respiratory and cardio-circulatory failure. An excessive systemic inflammatory response is observed during sepsis and after cardiopulmonary bypass (CPB) with similar clinical features. We hypothesized that hyperoxia condition encourages the systemic inflammatory response and organ disorder during ECMO. To prove this hypothesis correct, we investigated the systemic inflammatory responses at normal and high levels of arterial oxygen pressure (PaO) in the rat ECMO model.
Rats were randomly assigned to one of the following groups depending on the value of PaO during ECMO: A group (n=11, PaO 100-199 mmHg), B group (n=10, PaO 200-299 mmHg), C group (n=8, PaO 300-399 mmHg), and D group (n=11, PaO >400 mmHg). Serum cytokine levels [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)] were measured before, 60, and 120 min after the initiation of ECMO. The wet-to-dry weight (W/D) ratio of the left lung was also measured, and dihydroethidium (DHE) staining, reflecting superoxide generation, of lung and liver tissues was performed 120 min after ECMO initiation.
In the C and D groups, the pro-inflammatory cytokines (TNF-α and IL-6) significantly increased during ECMO compared with the other groups. On the other hand, the increase in anti-inflammatory cytokines (IL-10) was more suppressed in the C and D groups than in the other groups. The W/D ratio increased significantly more in the C and D groups than in the other groups. In addition, DHE fluorescence had a tendency to increase as the PaO rose.
These data demonstrate that it is better to avoid administration of too much oxygen during ECMO to attenuate lung injury linked to generation of superoxide and the systemic inflammatory response.
体外膜肺氧合（ECMO）越来越多地用于呼吸和心肺循环衰竭的机械支持。在脓毒症期间以及体外循环（CPB）后会观察到过度的全身炎症反应，二者具有相似的临床特征。我们推测高氧状态会在ECMO期间引发全身炎症反应和器官功能障碍。为了证明这一假设正确，我们在大鼠ECMO模型中研究了正常和高水平动脉血氧分压（PaO）时的全身炎症反应。
根据ECMO期间的PaO值，将大鼠随机分为以下几组：A组（n = 11，PaO 100 - 199 mmHg）、B组（n = 10，PaO 200 - 299 mmHg）、C组（n = 8，PaO 300 - 399 mmHg）和D组（n = 11，PaO > 400 mmHg）。在ECMO开始前、开始后60分钟和120分钟测量血清细胞因子水平[肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）]。还测量了左肺的湿重与干重（W/D）比值，并在ECMO开始120分钟后对肺和肝组织进行二氢乙锭（DHE）染色，以反映超氧化物的产生。
与其他组相比，C组和D组在ECMO期间促炎细胞因子（TNF-α和IL-6）显著增加。另一方面，C组和D组抗炎细胞因子（IL-10）的增加比其他组受到更明显的抑制。C组和D组的W/D比值比其他组显著增加更多。此外，随着PaO升高，DHE荧光有增加的趋势。
这些数据表明，在ECMO期间最好避免给予过多氧气，以减轻与超氧化物生成和全身炎症反应相关的肺损伤。
