Normandie Univ, UNIVROUEN, INSERM U1096, Rouen, France.
Rouen University Hospital, Department of Anaesthesia and Critical Care, Rouen, France.
Eur J Cardiothorac Surg. 2021 May 8;59(5):1037-1047. doi: 10.1093/ejcts/ezaa412.
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.
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.
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-1β, IL-10.
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.
缺血再灌注（IR）期间的内皮功能障碍是肺移植过程中原发性移植物功能障碍的主要原因。肺移植过程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影响尚不清楚。本研究旨在探讨 CPB 对肺 IR 大鼠模型内皮功能障碍的影响。
将大鼠分为 4 组：（i）假手术组，（ii）IR 组，（iii）CPB 组和（iv）IR-CPB 组。主要观察指标是通过测压法测量肺血管反应性。我们还通过酶联免疫吸附试验和电子显微镜评估糖萼降解，通过酶联免疫吸附试验和免疫组化评估全身和肺炎症。大鼠暴露于 45 分钟的 CPB 和 IR。我们使用 CPB 模型，允许股股支持并使左肺门缺血以进行 IR。
与 IR 组（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）相比，IR-CPB 组肺内皮依赖性乙酰胆碱舒张明显减少（10.7±9.1%），表明肺 IR 和 CPB 的联合增加了内皮功能障碍。在 IR-CPB、IR 和 CPB 组中，当抑制一氧化氮合酶时，血管舒张完全消失，表明这种舒张过程主要是由一氧化氮介导的。与其他组相比，IR-CPB 组的 syndecan-1 血浆水平升高，反映了糖萼的降解增加。我们还观察到 IR-CPB 组全身炎症增加，表现为血浆中 IL-1β、IL-10 水平升高。
CPB 显著增加了 IR 对肺内皮功能障碍的影响。因此，肺移植过程中使用 CPB 可能会增加内皮功能障碍，从而产生有害影响。
