Recovery of warm ischemic rat liver grafts by normothermic extracorporeal perfusion.

Recovery of warm ischemic rat liver grafts by normothermic extracorporeal perfusion.
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DOI:
10.1097/tp.0b013e318192df6b
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发表时间:
2009-01-27
期刊:
影响因子:
6.2
通讯作者:
Yarmush ML
Yarmush ML
中科院分区:
医学2区
文献类型:
--
作者:
Tolboom H;Pouw RE;Izamis ML;Milwid JM;Sharma N;Soto-Gutierrez A;Nahmias Y;Uygun K;Berthiaume F;Yarmush ML

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肝移植是目前唯一确定的治疗终末期肝病的方法,但它受到严重缺乏可行供体肝脏的限制。心脏性死亡(DCD)后的供体是一个未开发的来源,可以显着增加可用肝脏的池。通过常规静态冷藏(SCS)保存这些DCD肝脏与原发性无功能和延迟移植物失效的不可接受风险相关。常温体外肝脏灌注(NELP)被认为是SCS的一种改进。将从雄性刘易斯大鼠回收的肝脏进行1小时的热缺血,并用5小时的SCS或NELP保存,并移植到同基因受体中。作为额外的对照,移植用6小时SCS或NELP保存的非缺血性肝脏和未保存的缺血性肝脏。在NELP后,缺血损伤的肝脏可以原位移植到同基因受体中,4周后存活率为92%(N=13),这与接受SCS(N=9)或NELP(N=11)保存6小时的健康肝脏的对照动物相当。另一方面,缺血/SCS对照组的动物均在术后12小时内死亡(N=6)。类似地,接受缺血肝脏而不保存的动物在移植后24小时内全部死亡(N=6)。这些结果表明,NELP有可能回收热缺血肝脏,否则将无法移植。本研究中的大鼠模型是进一步优化NELP作为回收和保存DCD肝脏的方法的有用平台。
Liver transplantation is currently the only established treatment for end-stage liver disease, but it is limited by a severe shortage of viable donor livers. Donors after cardiac death (DCD) are an untapped source that could significantly increase the pool of available livers. Preservation of these DCD livers by conventional static cold storage (SCS) is associated with an unacceptable risk of primary non-function and delayed graft failure. Normothermic extracorporeal liver perfusion (NELP) has been suggested as an improvement over SCS. Livers recovered from male Lewis rats were subjected to 1hr of warm ischemia and preserved with 5hrs of SCS or NELP, and transplanted into syngeneic recipients. As additional controls, non-ischemic livers preserved with 6hrs of SCS or NELP and unpreserved ischemic livers were transplanted. Following NELP, ischemically damaged livers could be orthotopically transplanted into syngeneic recipients with 92% survival (N=13) after 4 weeks, which was comparable to control animals which received healthy livers preserved by SCS (N=9) or NELP (N=11) for 6hrs. On the other hand, animals from ischemia/SCS control group all died within 12hrs post-operatively (N=6). Similarly, animals that received ischemic livers without preservation all died within 24hrs after transplantation (N=6). These results suggest that NELP has the potential to reclaim warm ischemic livers that would not be transplantable otherwise. The rat model in this study is a useful platform to further optimize NELP as a method of recovery and preservation of DCD livers.