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机器灌注大鼠尸体肝脏移植的健康指数

A fitness index for transplantation of machine-perfused cadaveric rat livers.

作者信息

Perk Sinem, Izamis Maria-Louisa, Tolboom Herman, Uygun Basak, Yarmush Martin L, Uygun Korkut

机构信息

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Hospitals for Children, Boston, MA 02114, USA.

出版信息

BMC Res Notes. 2012 Jun 25;5:325. doi: 10.1186/1756-0500-5-325.

Abstract

BACKGROUND

The 110,000 patients currently on the transplant waiting list reflect the critical shortage of viable donor organs. However, a large pool of unused organs, from donors after cardiac death (DCD) that are disqualified because of extensive ischemic injury, may prove transplantable after machine perfusion treatment, fundamentally impacting the availability of treatment for end-stage organ failure. Machine perfusion is an ex-vivo organ preservation and treatment procedure that has the capacity to quantitatively evaluate and resuscitate cadaveric organs for transplantation.

METHODS

To diagnose whether an organ was fresh or ischemic, an initial assessment of liver quality was conducted via dynamic discriminant analysis. Subsequently, to determine whether the organs were sufficiently viable for successful implantation, fitness indices for transplantation were calculated based on squared prediction errors (SPE) for fresh and ischemic livers.

RESULTS

With just three perfusate metabolites, glucose, urea and lactate, the developed MPLSDA model distinguished livers as fresh or ischemic with 90% specificity. The SPE analyses revealed that fresh livers with SPE(F) < 10.03 and WI livers with SPE(WI) < 3.92 yield successful transplantation with 95% specificity.

CONCLUSIONS

The statistical methods used here can discriminate between fresh and ischemic livers based on simple metabolic indicators measured during perfusion. The result is a predictive fitness index for transplantation of rat livers procured after cardiac death. The translational implications of this study are that any donor organ procured from controlled, but most especially from uncontrolled cardiac death donors, will be objectively assessed and its recovery monitored over time, minimizing the critical loss of otherwise viable organs.

摘要

背景

目前有110,000名患者在移植等待名单上,这反映了可用供体器官的严重短缺。然而,大量因广泛缺血损伤而不合格的心脏死亡后供体(DCD)的未使用器官,在经过机器灌注处理后可能被证明可用于移植,这将从根本上影响终末期器官衰竭的治疗可及性。机器灌注是一种体外器官保存和治疗程序,有能力对用于移植的尸体器官进行定量评估和复苏。

方法

为了诊断器官是新鲜的还是缺血的,通过动态判别分析对肝脏质量进行了初步评估。随后,为了确定这些器官是否具有足够的活力以成功植入,基于新鲜和缺血肝脏的平方预测误差(SPE)计算移植适宜性指数。

结果

仅使用三种灌注液代谢物,即葡萄糖、尿素和乳酸,所开发的MPLSDA模型就能以90%的特异性区分新鲜肝脏和缺血肝脏。SPE分析显示,SPE(F) < 10.03的新鲜肝脏和SPE(WI) < 3.92的缺血肝脏移植成功率可达95%。

结论

这里使用的统计方法可以根据灌注过程中测量的简单代谢指标区分新鲜肝脏和缺血肝脏。结果得出了心脏死亡后获取的大鼠肝脏移植的预测适宜性指数。本研究的转化意义在于,任何从可控但尤其是不可控心脏死亡供体获取的供体器官,都将得到客观评估,并对其恢复情况进行长期监测,从而将原本可用器官的严重损失降至最低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f3a/3441584/e29115182f56/1756-0500-5-325-1.jpg

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