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Influence of perfusate on liver viability during hypothermic machine perfusion.

Abstract

AIM

To optimize the perfusates used for hypothermic machine perfusion (HMP).

METHODS

Sprague-Dawley rats were assigned randomly to three groups (n = 12 per group) that received either saline, University of Wisconsin cold-storage solution (UW) or histidine-tryptophan-ketoglutarate solution (HTK) as the perfusate. Each group was divided into two subgroups: static cold storage (SCS) and HMP (n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate (0-4 °C) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight (D/W) ratio, and malondialdehyde (MDA) and adenosine-triphosphate (ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups.

RESULTS

Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period (SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level (saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline (vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently (vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best (vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001).

CONCLUSION

HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP.

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  • Authors+Show Affiliations

    ,

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    ,

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    ,

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    ,

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    ,

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    ,

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    ,

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    ,

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    ,

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    Jun-Jun Jia, Jing Zhang, Jian-Hui Li, Ning He, Hai-Yang Xie, Lin Zhou, Shu-Sen Zheng, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.

    Source

    World journal of gastroenterology 21:29 2015 Aug 07 pg 8848-57

    MeSH

    Adenosine
    Adenosine Triphosphate
    Alanine Transaminase
    Allopurinol
    Animals
    Aspartate Aminotransferases
    Biomarkers
    Cold Ischemia
    Cold Temperature
    Glucose
    Glutathione
    Hepatectomy
    Insulin
    L-Lactate Dehydrogenase
    Liver
    Liver Function Tests
    Male
    Malondialdehyde
    Mannitol
    Organ Preservation
    Organ Preservation Solutions
    Perfusion
    Potassium Chloride
    Procaine
    Raffinose
    Rats, Sprague-Dawley
    Time Factors
    Tissue Survival

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    26269674

    Citation

    Jia, Jun-Jun, et al. "Influence of Perfusate On Liver Viability During Hypothermic Machine Perfusion." World Journal of Gastroenterology, vol. 21, no. 29, 2015, pp. 8848-57.
    Jia JJ, Zhang J, Li JH, et al. Influence of perfusate on liver viability during hypothermic machine perfusion. World J Gastroenterol. 2015;21(29):8848-57.
    Jia, J. J., Zhang, J., Li, J. H., Chen, X. D., Jiang, L., Zhou, Y. F., ... Zheng, S. S. (2015). Influence of perfusate on liver viability during hypothermic machine perfusion. World Journal of Gastroenterology, 21(29), pp. 8848-57. doi:10.3748/wjg.v21.i29.8848.
    Jia JJ, et al. Influence of Perfusate On Liver Viability During Hypothermic Machine Perfusion. World J Gastroenterol. 2015 Aug 7;21(29):8848-57. PubMed PMID: 26269674.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Influence of perfusate on liver viability during hypothermic machine perfusion. AU - Jia,Jun-Jun, AU - Zhang,Jing, AU - Li,Jian-Hui, AU - Chen,Xu-Dong, AU - Jiang,Li, AU - Zhou,Yan-Fei, AU - He,Ning, AU - Xie,Hai-Yang, AU - Zhou,Lin, AU - Zheng,Shu-Sen, PY - 2015/02/11/received PY - 2015/04/12/revised PY - 2015/06/09/accepted PY - 2015/8/14/entrez PY - 2015/8/14/pubmed PY - 2016/10/7/medline KW - Histidine-tryptophan-ketoglutarate solution KW - Hypothermic machine perfusion KW - Liver viability KW - Static cold storage KW - Wisconsin cold-storage solution SP - 8848 EP - 57 JF - World journal of gastroenterology JO - World J. Gastroenterol. VL - 21 IS - 29 N2 - AIM: To optimize the perfusates used for hypothermic machine perfusion (HMP). METHODS: Sprague-Dawley rats were assigned randomly to three groups (n = 12 per group) that received either saline, University of Wisconsin cold-storage solution (UW) or histidine-tryptophan-ketoglutarate solution (HTK) as the perfusate. Each group was divided into two subgroups: static cold storage (SCS) and HMP (n = 6 per subgroup). The liver graft was retrieved according to the method described by Kamada. For the SCS group, the graft was directly placed into cold perfusate (0-4 °C) for 6 h after liver isolation while the portal vein of the graft was connected to the perfusion machine for the HMP group. Then the perfusates were collected at different time points for analysis of aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) levels. Liver tissues were obtained for evaluation of histology, dry/wet weight (D/W) ratio, and malondialdehyde (MDA) and adenosine-triphosphate (ATP) levels. The portal vein pressure and velocity were monitored in real time in all HMP subgroups. RESULTS: Comparison of HMP and SCS: Regardless of the perfusate, HMP improved the architecture of donor graft in reducing the congestion around sinusoids and central vein and maintaining sinusoid lining in morphology; HMP improved liver function in terms of ALT, AST and LDH, especially during the 3-6 h period (SCS vs HMP using saline: ALT3, 225.00 ± 105.62 vs 49.50 ± 18.50, P = 0.047; LDH3, 1362.17 ± 563.30 vs 325.75 ± 147.43, P = 0.041; UW: LDH6, 2880.14 ± 948.46 vs 2135.00 ± 174.27, P = 0.049; HTK, AST6, 307.50 ± 52.95 vs 185.20 ± 20.46, P = 0.041); HMP decreased MDA level (saline, 2.79 ± 0.30 vs 1.09 ± 0.09, P = 0.008; UW, 3.01 ± 0.77 vs 1.23 ± 0.68, P = 0.005; HTK, 3.30 ± 0.52 vs 1.56 ± 0.22, P = 0.006). Comparison among HMP subgroups: HTK showed less portal vein resistance than UW and saline (vs saline, 3.41 ± 0.49 vs 5.00 ± 0.38, P < 0.001; vs UW, 3.41 ± 0.49 vs 4.52 ± 0.63, P = 0.007); UW reduced edema most efficiently (vs saline, 0.68 ± 0.02 vs 0.79 ± 0.05, P = 0.013), while HTK maintained ATP levels best (vs saline, 622.60 ± 29.11 vs 327.43 ± 44.66, P < 0.001; vs UW, 622.60 ± 29.11 vs 301.80 ± 37.68, P < 0.001). CONCLUSION: HMP is superior to SCS in maintaining both architecture and function of liver grafts. Further, HTK was found to be the optimal perfusate for HMP. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/26269674/Influence_of_perfusate_on_liver_viability_during_hypothermic_machine_perfusion_ L2 - http://www.wjgnet.com/1007-9327/full/v21/i29/8848.htm DB - PRIME DP - Unbound Medicine ER -