当前位置: X-MOL 学术PLOS ONE › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Dual versus single vessel normothermic ex vivo perfusion of rat liver grafts using metamizole for vasodilatation.
PLOS ONE ( IF 3.7 ) Pub Date : 2020-07-02 , DOI: 10.1371/journal.pone.0235635
Felix Claussen 1 , Joseph M G V Gassner 1 , Simon Moosburner 1 , David Wyrwal 1 , Maximilian Nösser 1 , Peter Tang 1 , Lara Wegener 1 , Julian Pohl 1 , Anja Reutzel-Selke 1 , Ruza Arsenic 2 , Johann Pratschke 1 , Igor M Sauer 1 , Nathanael Raschzok 1, 3
Affiliation  

Background

Normothermic ex vivo liver perfusion (NEVLP) is a promising strategy to increase the donor pool in liver transplantation. Small animal models are essential to further investigate questions regarding organ preservation and reconditioning by NEVLP. A dual vessel small animal NEVLP (dNEVLP) model was developed using metamizole as a vasodilator and compared to conventional portovenous single vessel NEVLP (sNEVLP).

Methods

Livers of male Wistar rats were perfused with erythrocyte-supplemented culture medium for six hours by either dNEVLP via hepatic artery and portal vein or portovenous sNEVLP. dNEVLP was performed either with or without metamizole treatment. Perfusion pressure and flow rates were constantly monitored. Transaminase levels were determined in the perfusate at the start and after three and six hours of perfusion. Bile secretion was monitored and bile LDH and GGT levels were measured hourly. Histopathological analysis was performed using liver and bile duct tissue samples after perfusion.

Results

Hepatic artery pressure was significantly lower in dNEVLP with metamizole administration. Compared to sNEVLP, dNEVLP with metamizole treatment showed higher bile production, lower levels of transaminases during and after perfusion as well as significantly lower necrosis in liver and bile duct tissue. Biochemical markers of bile duct injury showed the same trend.

Conclusion

Our miniaturized dNEVLP system enables normothermic dual vessel rat liver perfusion. The administration of metamizole effectively ameliorates arterial vasospasm allowing for six hours of dNEVLP, with superior outcome compared to sNEVLP.



中文翻译:

使用metamizole进行血管扩张的大鼠肝移植物的双血管和单血管常温离体灌注。

背景

常温离体肝脏灌注(NEVLP)是一种有希望的策略,可以增加肝脏移植中的供体库。小动物模型对于进一步调查有关NEVLP的器官保存和修复的问题至关重要。使用metamizole作为血管扩张剂开发了双血管小动物NEVLP(dNEVLP)模型,并将其与常规的静脉单血管NEVLP(sNEVLP)进行了比较。

方法

dNEVLP经由肝动脉和门静脉或门静脉sNEVLP向雄性Wistar大鼠的肝脏灌入补充了红细胞的培养基6小时。dNEVLP在进行或不进行metamizole治疗的情况下进行。持续监测灌注压力和流速。在灌流开始时以及灌流三,六小时后确定灌流液中的转氨酶水平。监测胆汁分泌并每小时测量胆汁LDH和GGT水平。灌注后使用肝脏和胆管组织样本进行组织病理学分析。

结果

给予间咪唑的dNEVLP组肝动脉压明显降低。与sNEVLP相比,采用咪唑类药物治疗的dNEVLP表现出更高的胆汁生成量,灌注过程中和灌注后的转氨酶水平较低,以及肝脏和胆管组织中的坏死率明显降低。胆管损伤的生化标志物显示了相同的趋势。

结论

我们的微型dNEVLP系统可实现正常体温的双血管大鼠肝灌注。施用metamizole可有效改善动脉血管痉挛,使dNEVLP持续6小时,与sNEVLP相比,结局更佳。

更新日期:2020-07-03
down
wechat
bug