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中华重症医学电子杂志 ›› 2017, Vol. 03 ›› Issue (02) : 116 -121. doi: 10.3877/cma.j.issn.2096-1537.2017.02.008

所属专题: 文献

基础研究

脑心双死亡器官捐献肝损伤状态犬体外膜式氧合模型的建立
朱艳平1, 曹璐2, 姚纪友1, 唐云华3, 胡晓光1, 蔡常洁1, 童荔1,()   
  1. 1. 510080 广州,中山大学附属第一医院重症二科
    2. 510080 广州,中山大学附属第一医院体外循环科
    3. 510080 广州,中山大学附属第一医院器官移植科
  • 收稿日期:2017-05-03 出版日期:2017-05-28
  • 通信作者: 童荔
  • 基金资助:
    广东省科技计划项目(20130607c)

Extracorporeal membrane oxygenation model establishment of dogs on basis of donation after brain-cardiac death with liver injury

Yanping Zhu1, Lu Cao2, Jiyou Yao1, Yunhua Tang3, Xiaoguang Hu1, Changjie Cai1, Li Tong1,()   

  1. 1. The 2nd Department of Critical Care Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
    2. Department of Extracorporeal Circulation, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
    3. Department of Organ Transplantation, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
  • Received:2017-05-03 Published:2017-05-28
  • Corresponding author: Li Tong
  • About author:
    Corresponding author: Tong Li, Email:
引用本文:

朱艳平, 曹璐, 姚纪友, 唐云华, 胡晓光, 蔡常洁, 童荔. 脑心双死亡器官捐献肝损伤状态犬体外膜式氧合模型的建立[J/OL]. 中华重症医学电子杂志, 2017, 03(02): 116-121.

Yanping Zhu, Lu Cao, Jiyou Yao, Yunhua Tang, Xiaoguang Hu, Changjie Cai, Li Tong. Extracorporeal membrane oxygenation model establishment of dogs on basis of donation after brain-cardiac death with liver injury[J/OL]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2017, 03(02): 116-121.

目的

在稳定的犬脑心双死亡器官捐献(DBCD)肝损伤基础上,建立体外膜式氧合(ECMO)循环系统。

方法

20只比格犬,首先采用缓慢颅内加压法诱导脑死亡,确认脑死亡后,放置ECMO动静脉插管,采用Pringle法,阻断门静脉和肝动脉血流60 min,造成DBCD肝损伤模型,连接ECMO建立循环系统。采集阻断前后血标本进行血气分析,检测乳酸、钠离子、钾离子、钙离子、血糖浓度,同时检测血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、乳酸脱氢酶(LDH)浓度和肿瘤坏死因子α(TNF-α)、白介素6(IL-6)浓度,并采用Student′s t检验比较。

结果

20只犬脑死亡判定均成功。2只犬在建立肝损伤时,开放阻断钳后心跳骤停死亡,余18只均在DBCD肝损伤基础上成功建立ECMO循环系统,成功率为90.0%(18/20)。与阻断前比较,肝脏出现明显的缺血缺氧表现,乳酸浓度上升[(4.57±0.35)mmol/L vs (1.18±0.15)mmol/L],且差异有统计学意义(t=8.91,P<0.001);ALT、AST、LDH浓度均上升[(400.40±15.13)U/L vs (27.40±1.98)U/L,(444.75±19.65)U/L vs (25.40±0.98)U/L,(274.00±19.54)U/L vs (55.17±6.26)U/L],且差异均有统计学意义(t=24.45、21.32、10.67,P均<0.001);TNF-α、IL-6浓度也均升高[(29.23±1.85)pg/ml vs (8.37±1.30)pg/ml,(5.54 ±1.11)pg/ml vs (2.25±0.81)pg/ml],且差异有统计学意义(t=9.21,P<0.001;t=2.39,P=0.03)。

结论

本研究成功建立脑心双死亡肝损伤状态下ECMO循环系统动物模型,为DBCD肝损伤ECMO修复研究奠定基础。

Objective

To establish extracorporeal membrane oxygenation (ECMO) circulatory system on the basis of donation after brain death plus cardiac death (DBCD) with liver injury in dogs.

Methods

Brain death model via increasing intracranial pressure gradually were replicated in 20 male dogs. After confirming the brain death, femoral arteriovenous ECMO catheters were inserted. Pringle-Maneuver was used to block the portal vein and hepatic artery flow for 60 minutes. Extracorporeal membrane oxygenation system was established on the basis of DBCD with liver injury. Levels of lactate, Na+, K+, Ca2+, Glucose, alanine aminotransferase (ALT), aspartic transaminase (AST), lactic dehydrogenase (LDH), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) before and after the blockade was measured. Student′s t test was used to analyze the data.

Results

Brain death model were replicated successfully in all 20 dogs, among which 2 died of cardiac arrest after clamp removed. ECMO system was established successfully in 18 (90.0%) dogs. 60 minutes after blockade, the liver appeared obvious hypoxic-ischemic manifestation. Blood lactate concentration was significant higher after blockade [(4.57±0.35) mmol/L vs (1.18±0.15) mmol/L, t=8.91, P<0.001] as well as the level of ALT, AST and LDH [(400.40±15.13) U/L vs (27.40±1.98) U/L, (444.75±19.65) U/L vs (25.40±0.98) U/L, (274.00±19.54) U/L vs (55.17±6.26) U/L, t=24.45, 21.32, 10.67, all P<0.001]. The TNF-α and IL-6 concentration were also significant higher after blockade compare to the baseline [(29.23±1.85) pg/ml vs (8.37±1.30) pg/ml, t=9.21, P<0.001; (5.54±1.11) pg/ml vs (2.25±0.81) pg/ml, t=2.39, P=0.03].

Conclusion

This study successfully established a liver injury model with brain death, which provides an ideal model to investigate the protection of ECMO on DBCD donors with liver injury.

图1,2 脑死亡诱导前后脑电图。图1示诱导前,当疼痛刺激时脑电活动出现强烈波动反应;图2示诱导后静息状态,给予疼痛刺激时脑电图波形未见明显波动
图4 肝脏阻断过程中,肝脏颜色变化为暗红色,肿胀
表1 第一肝门阻断前后犬血气分析指标变化(mmol/L,±s
表2 第一肝门阻断前后犬肝功能指标、炎症因子浓度变化(±s
1
刘永锋. 心脏死亡供者器官移植现状及展望[J]. 中华普通外科杂志, 2013, 28(3): 169-172.
2
Fan X, Chen Z, Nasralla D, et al. The organ preservation and enhancement of donation success ratio effect of extracorporeal membrane oxygenation in circulatory unstable brain death donor[J]. Clin Transplant, 2016, 30(10): 1306-1313.
3
Kolkert JL, ′t Hart NA, van Dijk A, et al. The gradual onset brain death model: a relevant model to study organ donation and its consequences on the outcome after transplantation[J]. Lab Anim, 2007, 41(3): 363-371.
4
Pratschke J, Wilhelm MJ, Kusaka M, et al. A model of gradual onset brain death for transplant-associated studies in rats[J]. Transplantation, 2000, 69(3): 427-430.
5
国家卫生和计划生育委员会脑损伤质控评价中心. 脑死亡判定标准与技术规范(成人质控版)[J]. 中国现代神经疾病杂志, 2015, 15(12): 935-939.
6
Spiegel HU, Bahde R. Experimental models of temporary normothermic liver ischemia[J]. J Invest Surg, 2006, 19(2): 113-123.
7
朱艳平,曹璐,胡晓光, 等. 经股动静脉置管犬体外膜肺氧合模型的建立[J/CD]. 中华普通外科学文献(电子版), 2016, 10(1): 19-23.
8
Shemie SD, Hornby L, Baker A, et al. International guideline development for the determination of death[J]. Intensive Care Med, 2014, 40(6): 788-797.
9
中华人民共和国国家卫生和计划生育委员会, 国家卫生计生委医政医管局. 卫生部办公厅关于启动心脏死亡捐献器官移植试点工作的通知[EB/OL]. (2011-05-03)

URL    
10
Mackersie RC, Bronsther OL, Shackford SR. Organ procurement in patients with fatal head injuries. The fate of the potential donor[J]. Ann Surg, 1991, 213(2): 143-150.
11
Teng-Wei C, Chung-Bao H, Chan DC, et al. Marked elevation of hepatic transaminases in recipients of an orthotopic liver transplant from a brain-dead donor receiving extracorporeal membrane oxygenation[J]. Ann Transplant, 2014, 19: 680-687.
12
孙煦勇,秦科,董建辉, 等. 体外膜肺氧合用于循环功能不稳定的中国一类捐赠者的器官保护三例[J]. 中华器官移植杂志, 2012, 33(11): 657-660.
13
Hsieh CE, Lin HC, Tsui YC, et al. Extracorporeal membrane oxygenation support in potential organ donors for brain death determination[J]. Transplant Proc, 2011, 43(7): 2495-2498.
14
Lee H, Cho YH, Sung K, et al. The Use of Extracorporeal Circulation in Suspected Brain Dead Organ Donors with Cardiopulmonary Collapse[J]. J Korean Med Sci, 2015, 30(12): 1911-1914.
15
Migliaccio ML, Zagli G, Cianchi G, et al. Extracorporeal membrane oxygenation in brain-death organ and tissues donors: a single-centre experience[J]. Br J Anaesth, 2013, 111(4): 673-674.
16
Kang JH, Choi BH, Moon KM, et al. Beneficial Effect of Extracorporeal Membrane Oxygenation on Organ Perfusion During Management of the Unstable Brain-dead Donor: A Case Series[J]. Transplant Proc, 2016, 48(7): 2458-2460.
17
Jiménez-Castro MB, Gracia-Sancho J, Peralta C. Brain death and marginal grafts in liver transplantation[J]. Cell Death Dis, 2015, 6(6): e1777.
18
van Der Hoeven JA, Ter Horst GJ, Molema G, et al. Effects of brain death and hemodynamic status on function and immunologic activation of the potential donor liver in the rat[J]. Ann Surg, 2000, 232(6): 804-813.
19
Pratschke J, Neuhaus P, Tullius SG. What can be learned from brain-death models?[J]. Transpl Int, 2005,18(1): 15-21.
20
Gasser M, Waaga AM, Laskowski IA, et al. The influence of donor brain death on short and long-term outcome of solid organ allografts[J]. Ann Transplant, 2000, 5(4): 61-67.
21
van Riel WG, van Golen RF, Reiniers MJ, et al. How much ischemia can the liver tolerate during resection?[J]. Hepatobiliary Surg Nutr, 2016, 5(1): 58-71.
22
Carlessi R, Lemos NE, Dias AL, et al. Exendin-4 attenuates brain death-induced liver damage in the rat[J]. Liver Transpl, 2015, 21(11): 1410-1418.
23
Spiegel HU, Bahde R. Experimental models of temporary normothermic liver ischemia[J]. J Invest Surg, 2009, 19(2): 113-123.
24
Hafez T, Moussa M, Nesim I, et al. The effect of intraportal prostaglandin E1 on adhesion molecule expression, inflammatory modulator function, and histology in canine hepatic ischemia/reperfusion injury[J]. J Surg Res, 2007, 138(1): 88-99.
25
Tsung A, Klune JR, Zhang X, et al. HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling[J]. J Exp Med, 2007, 204(12): 2913-2923.
26
Peralta C, Jimenez-Castro MB, Gracia-Sancho J. Hepatic ischemia and reperfusion injury: effects on the liver sinusoidal milieu[J]. J Hepatol, 2013, 59(5): 1094-1106.
27
Li J, Zhang S, Wu Y, et al. Protective effects of N-acetylcysteine on the liver of brain-dead Ba-Ma mini pig[J]. Transplant Proc, 2010, 42(1): 195-199.
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