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低温机器灌注人类供肝会影响肝血窦内皮损伤和微生物感染的风险吗?一项评估血流参数、无菌状态和肝血窦内皮超微结构的可行性研究。

Does hypothermic machine perfusion of human donor livers affect risks of sinusoidal endothelial injury and microbial infection? A feasibility study assessing flow parameters, sterility, and sinusoidal endothelial ultrastructure.

作者信息

Jomaa A, Gurusamy K, Siriwardana P N, Claworthy I, Collier S, de Muylder P, Fuller B, Davidson B

机构信息

LIVET Group, Division of Surgery and Interventional Sciences, Royal Free Hospital, London, United Kingdom.

出版信息

Transplant Proc. 2013 Jun;45(5):1677-83. doi: 10.1016/j.transproceed.2013.01.011.

DOI:10.1016/j.transproceed.2013.01.011
PMID:23769023
Abstract

BACKGROUND

Hypothermic machine perfusion (HMP) is better than conventional cold storage in kidney transplantation. Large animal models suggest that HMP may be beneficial for the liver as well, but questions remain about perfusion mode (dual portal/arterial flow versus single flow) and hepatic vascular injury including endothelial dysfunction or potential microbial infectivity during HMP.

METHODS

Sixteen human livers rejected for transplantation by all UK centers with appropriate consent for research were randomized into 4 groups (n = 4 each): group 1: ≥7 hours cold storage (CS) and 1 hour HMP through hepatic artery (HA) alone; group 2: ≥7 hours CS and 1 hour HMP through HA and portal vein (PV); group 3: ≥7 hours CS and 1 hour HMP through PV alone; and group 4: ≥8 hours CS. A pressure-controlled prototype based on Lifeport Kidney Transporter (Organ Recovery Systems) was used. Livers were perfused at 4-8°C under sterile conditions with Belzer MPS KPS-1. Perfusion parameters (pressure, flow, resistance, and temperature) were recorded every 15 minutes. Perfusate for microbial culture and sensitivity were taken before and after HMP. Electron microscopy of 3 liver biopsy samples taken before perfusion, were compared with 3 samples from adjacent areas after perfusion.

RESULTS

Preset HA pressure of 30 mm Hg and PV pressure of 7 mm Hg were maintained throughout the perfusion. HA and PV flow ranged, respectively, from 11 to 107 mL/min (mean 59.5) and 39 to 199 mL/min (mean 96.2), with no differences between groups. The same was true for resistance: HA and PV resistance ranged, respectively from 0.17 to 1.99 mm Hg/mL/min (mean 0.71) and 0.07 to 0.17 mm Hg/mL/min (mean 0.08). Temperature was maintained at 4-8°C with the use of an external heat exchanger. No difference in sinusoidal endothelial ultrastructure was seen before and after machine perfusion or between any of the groups. Sterility was maintained throughout the HMP.

CONCLUSIONS

HMP of human livers did not produce evidence of sinusoidal endothelial injury or breach of sterility. Single or dual perfusion modes did not affect vascular resistance or flow. The results suggest that further studies of HMP with human livers are warranted.

摘要

背景

在肾移植中,低温机器灌注(HMP)优于传统冷保存。大型动物模型表明,HMP对肝脏可能也有益,但关于灌注模式(双门静脉/动脉血流与单一流)以及HMP期间的肝血管损伤,包括内皮功能障碍或潜在的微生物感染性,仍存在疑问。

方法

16个被英国所有移植中心拒绝用于移植但已获得适当研究同意的人类肝脏被随机分为4组(每组n = 4):第1组:≥7小时冷保存(CS)并仅通过肝动脉(HA)进行1小时HMP;第2组:≥7小时CS并通过HA和门静脉(PV)进行1小时HMP;第3组:≥7小时CS并仅通过PV进行1小时HMP;第4组:≥8小时CS。使用基于Lifeport肾脏转运器(器官回收系统)的压力控制原型。肝脏在无菌条件下于4 - 8°C用Belzer MPS KPS - 1灌注。每15分钟记录灌注参数(压力、流量、阻力和温度)。在HMP前后采集用于微生物培养和药敏试验的灌注液。将灌注前采集的3份肝脏活检样本的电子显微镜检查结果与灌注后相邻区域的3份样本进行比较。

结果

在整个灌注过程中,HA预设压力为30 mmHg,PV预设压力为7 mmHg得以维持。HA和PV流量分别为11至107 mL/分钟(平均59.5)和39至199 mL/分钟(平均96.2),各组之间无差异。阻力情况相同:HA和PV阻力分别为0.17至1.99 mmHg/mL/分钟(平均0.71)和0.07至0.17 mmHg/mL/分钟(平均0.08)。通过使用外部热交换器将温度维持在4 - 8°C。在机器灌注前后或任何组之间,未观察到肝血窦内皮超微结构有差异。在整个HMP过程中保持了无菌状态。

结论

人类肝脏的HMP未产生肝血窦内皮损伤或无菌状态被破坏的证据。单灌注或双灌注模式均未影响血管阻力或流量。结果表明有必要对人类肝脏的HMP进行进一步研究。

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