Cardiopulmonary bypass increases endothelial dysfunction after pulmonary ischaemia-reperfusion in an animal model
Cardiopulmonary bypass increases endothelial dysfunction after pulmonary ischaemia-reperfusion in an animal model
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DOI：
10.1093/ejcts/ezaa412
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发表时间：
2021-05-01
影响因子：
3.4
通讯作者：
Baste, Jean-Marc
中科院分区：
文献类型：
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作者：
Selim, Jean;Hamzaoui, Mouad;Baste, Jean-Marc
结论：缺血再灌注（IR）期间的内皮功能障碍是肺移植期间原发性移植物功能障碍的主要原因。肺移植术中常规使用体外循环（CPB）仍存在争议。然而，CPB对肺内皮功能障碍的贡献仍不清楚。目的是研究CPB对肺IR大鼠模型内皮功能障碍的影响。方法：大鼠分为4组：（i）假手术组，（ii）IR组，（iii）CPB组和（iv）IR-CPB组。主要结果是通过钢丝肌电描记器研究肺血管反应性。我们还通过酶联免疫吸附试验和电子显微镜评估了糖萼降解，通过酶联免疫吸附试验和免疫组织化学评估了全身和肺部炎症。将大鼠暴露于45 min的CPB和IR。我们使用允许股-股支撑的CPB模型，左肺门缺血用于IR。结果：IR-CPB组肺血管内皮对乙酰胆碱的依赖性舒张反应明显减弱（10.7 +/- 9.1%）与IR组相比（50.5 ± 5.2%，P < 0.001），CPB组（54.1 ± 4.7%，P < 0.001）和假手术组（80.8 ± 6.7%，P < 0.001），表明肺IR和CPB的相关性增加了内皮功能障碍。在IR-CPB、IR和CPB组中，抑制一氧化氮合酶可完全消除血管舒张作用，提示这一舒张过程主要由一氧化氮介导。与其他组相比，我们观察到IR-CPB组中的多配体蛋白聚糖-1血浆水平更高，反映了糖萼的降解增加。我们还观察到IR-CPB组中更高的全身炎症反应，如升高的血浆IL-1 β、IL-10水平。结论：CPB显著增加了IR介导的肺内皮功能障碍。因此，在肺移植期间使用CPB可能是有害的，因为会增加内皮功能障碍。
OBJECTIVES: Endothelial dysfunction during ischaemia-reperfusion (IR) is a major cause of primary graft dysfunction during lung transplantation. The routine use of cardiopulmonary bypass (CPB) during lung transplantation remains controversial. However, the contribution of CPB to pulmonary endothelial dysfunction remains unclear. The objective was to investigate the impact of CPB on endothelial dysfunction in a lung IR rat model.METHODS: Rats were allocated to 4 groups: (i) Sham, (ii) IR, (iii) CPB and (iv) IR-CPB. The primary outcome was the study of pulmonary vascular reactivity by wire myograph. We also assessed glycocalyx degradation by enzyme-linked immunosorbent assay and electron microscopy and both systemic and pulmonary inflammation by enzyme-linked immunosorbent assay and immunohistochemistry. Rats were exposed to 45 min of CPB and IR. We used a CPB model allowing femoro-femoral support with left pulmonary hilum ischaemia for IR.RESULTS: Pulmonary endothelium-dependent relaxation to acetylcholine was markedly reduced in the IR-CPB group (10.7 +/- 9.1%) compared to the IR group (50.5 +/- 5.2%, P < 0.001), the CPB group (54.1 +/- 4.7%, P < 0.001) and the sham group (80.8 +/- 6.7%, P < 0.001), suggesting that the association of pulmonary IR and CPB increases endothelial dysfunction. In IR-CPB, IR and CPB groups, vasorelaxation was completely abolished when inhibiting nitric oxide synthase, suggesting that this relaxation process was mainly mediated by nitric oxide. We observed higher syndecan-1 plasma levels in the IR-CPB group in comparison with the other groups, reflecting an increased degradation of glycocalyx. We also observed higher systemic inflammation in the IR-CPB group as shown by the increased plasma levels of IL-1 beta, IL-10.CONCLUSIONS: CPB significantly increased the IR-mediated effects on pulmonary endothelial dysfunction. Therefore, the use of CPB during lung transplantation could be deleterious, by increasing endothelial dysfunction.