Multi Organ Transplant Program, Toronto General Hospital, Toronto, ON, Canada.
Programa de Doctorat en Cirurgia i Ciències Morfològiques de la Universitat Autònoma de Barcelona, Barcelona, Spain.
Transplantation. 2018 Apr;102(4):601-608. doi: 10.1097/TP.0000000000002021.
The optimal vasodilator to avoid hepatic artery vasospasm during normothermic ex vivo liver perfusion (NEVLP) is yet to be determined. We compared safety and efficacy of BQ123 (endothelin1 antagonist), epoprostenol (prostacyclin analogue), and verapamil (calcium channel antagonist).
Livers from porcine heart beating donors were perfused for 3 hours and transplanted into recipient pigs. Four groups were compared: group 1, livers perfused with a dose of 1.25 mg of BQ123 at baseline and at 2 hours of perfusion; group 2, epoprostenol at a continuous infusion of 4 mg/h; group 3, verapamil 2.5 mg at baseline and at 2 hours of perfusion; group 4, no vasodilator used during ex vivo perfusion. Liver injury and function were assessed during perfusion, and daily posttransplantation until postoperative day (POD) 3. All groups were compared with a cold storage group for postoperative graft function.
Hepatic artery flow during NEVLP was significantly higher in BQ123 compared with verapamil, epoprostenol, and no vasodilator-treated livers. Aspartate aminotransferase levels were significantly lower with BQ123 and verapamil compared with epoprostenol and control group during perfusion. Peak aspartate aminotransferase levels were lower in pigs receiving BQ123 and verapamil perfused grafts compared with epoprostenol and control group. International Normalized Ratio, alkaline phosphatase, and total bilirubin levels were lower in the BQ123 and verapamil groups compared to epoprostenol group. Cold storage group had increased markers of ischemia reperfusion injury and slower graft function recovery compared to machine perfused grafts.
The use of BQ123, epoprostenol, and verapamil during NEVLP is safe. Livers perfused with BQ123 and verapamil have higher hepatic artery flow and reduced hepatocyte injury during perfusion compared with epoprostenol. Hepatic artery flow is significantly reduced in the absence of vasodilators during NEVLP.
在常温离体肝脏灌注（NEVLP）期间，避免肝动脉痉挛的最佳血管扩张剂尚未确定。我们比较了 BQ123（内皮素 1 拮抗剂）、依前列醇（前列环素类似物）和维拉帕米（钙通道拮抗剂）的安全性和疗效。
从心脏跳动的供体猪中取出肝脏，灌注 3 小时后移植到受体猪中。比较了四组：组 1，在灌注开始时和灌注 2 小时时给予 1.25mg 的 BQ123；组 2，连续输注 4mg/h 的依前列醇；组 3，在灌注开始时和灌注 2 小时时给予 2.5mg 的维拉帕米；组 4，在离体灌注期间不使用血管扩张剂。在灌注期间评估肝损伤和肝功能，并在移植后每天（POD）直到第 3 天。所有组均与冷存储组进行术后移植物功能比较。
与维拉帕米、依前列醇和无血管扩张剂处理的肝脏相比，BQ123 在 NEVLP 期间肝动脉流量显著增加。与依前列醇和对照组相比，在灌注期间，BQ123 和维拉帕米组的天冬氨酸转氨酶水平显著降低。接受 BQ123 和维拉帕米灌注的猪的天冬氨酸转氨酶峰值水平低于依前列醇和对照组。与依前列醇组相比，BQ123 和维拉帕米组的国际标准化比值、碱性磷酸酶和总胆红素水平较低。与机器灌注的移植物相比，冷存储组的缺血再灌注损伤标志物增加，移植物功能恢复较慢。
在 NEVLP 期间使用 BQ123、依前列醇和维拉帕米是安全的。与依前列醇相比，BQ123 和维拉帕米灌注的肝脏在灌注期间具有更高的肝动脉流量和降低的肝细胞损伤。在 NEVLP 期间，如果不使用血管扩张剂，肝动脉流量会显著降低。
