1 Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany. 2 Clinic of Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria. 3 Faculty of Medicine, Philipps-University, Marburg, Germany. 4 Address correspondence to: Patrick Paulus, M.D., Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
Transplantation. 2014 May 15;97(9):908-16. doi: 10.1097/TP.0000000000000056.
Ischemia-reperfusion edema is a common early complication after lung transplantation where the hypoxia-induced vascular endothelial growth factor (VEGF)-A plays a pivotal role. It remains unclear whether a VEGF blockade is beneficial in lung transplantation.
VEGF-A blockade was investigated in an orthotopic rat model of lung transplantation. VEGF-A antibody was added into the preservation solution alone (α-VEGF D/-), in the preservation solution and systemically to the recipient before reperfusion (α-VEGF D/R), or applied to the recipient alone before reperfusion (α-VEGF -/R). Forty-eight hours after lung transplantation, left lungs were collected and wet-to-dry ratio, Western blotting, RT-PCR, and immunohistology were performed.
VEGF-A blockade in α-VEGF D/-, α-VEGF D/R, and α-VEGF -/R resulted in neutralization of tissue VEGF-A. Reperfusion edema was only reduced in α-VEGF D/R and α-VEGF D/- groups versus Perfadex controls. Some α-VEGF -/R rats showed a hyperinflammation leading to increased pro-inflammatory cytokine expressions as well as increased edema. Whereas generally the α-VEGF D/- group showed decreased inflammation, the combination with anti-VEGF treatment to the recipient resulted in a pro-inflammatory and a pro-apoptotic phenotype. Short-term survival, however, was not significantly different in all groups as compared to the controls. In the α-VEGF (D/R) or (D/-) groups, animals mainly died from arterial thromboembolisms and in the α-VEGF (-/R) group, hyperinflammation was the main cause of death.
VEGF-A directly contributes to the formation of a reperfusion edema, which might be reduced by its blockade. However, the α-VEGF effect on the endothelial integrity might also favor arterial thrombosis formation.
缺血再灌注水肿是肺移植后常见的早期并发症，其中缺氧诱导的血管内皮生长因子（VEGF-A）起着关键作用。目前尚不清楚 VEGF 阻断是否对肺移植有益。
在肺移植的原位大鼠模型中研究了 VEGF-A 阻断。单独在保存液中添加 VEGF-A 抗体（α-VEGF D/-），在保存液和受体中再灌注前系统添加（α-VEGF D/R），或单独在再灌注前应用于受体（α-VEGF -/R）。肺移植后 48 小时，收集左肺，进行湿重/干重比、Western blot、RT-PCR 和免疫组织化学检测。
α-VEGF D/-、α-VEGF D/R 和 α-VEGF -/R 中的 VEGF-A 阻断导致组织 VEGF-A 中和。仅在α-VEGF D/R 和α-VEGF D/-组中，再灌注水肿与 Perfadex 对照相比有所减轻。一些α-VEGF -/R 大鼠表现出过度炎症，导致促炎细胞因子表达增加和水肿增加。虽然一般情况下，α-VEGF D/-组炎症减少，但与受体的抗 VEGF 治疗相结合导致促炎和促凋亡表型。然而，与对照组相比，所有组的短期生存率均无显著差异。在α-VEGF（D/R）或（D/-）组中，动物主要死于动脉血栓栓塞，而在α-VEGF（-/R）组中，过度炎症是死亡的主要原因。
VEGF-A 直接促成再灌注水肿的形成，阻断 VEGF-A 可能会减轻这种水肿。然而，VEGF-A 对内皮完整性的影响也可能有利于动脉血栓形成。
