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Improved preservation of warm ischemic livers by hypothermic machine perfusion with supplemented University of Wisconsin solution.
J Invest Surg. 2008 Mar-Apr; 21(2):83-91.JI

Abstract

Hypothermic machine perfusion (HMP) has the potential to improve recovery and preservation of Donation after Cardiac Death (DCD) livers, including uncontrolled DCD livers. However, current perfusion solutions lack the needed substrates to improve energy recovery and minimize hepatic injury, if warm ischemic time (WIT) is extended. This proof-of-concept study tested the hypothesis that the University of Wisconsin (UW) solution supplemented with anaplerotic substrates, calcium chloride, thromboxane A2 inhibitor, and antioxidants could improve HMP preservation and minimize reperfusion injury of warm ischemic livers. Preflushed rat livers subjected to 60 min WIT were preserved for 5 h with standard UW or supplemented UW (SUW) solution. Post preservation hepatic functions and viability were assessed during isolated perfusion with Krebs-Henseleit solution. Livers preserved with SUW showed significantly (p < .001) improved recovery of tissue ATP levels (micromol/g liver), 2.06 +/- 0.10 (mean +/- SE), as compared to the UW group, 0.70 +/- 0.10, and the level was 80% of that of fresh control livers (2.60 +/- 0.13). At the end of 1 h of rewarming, lactate dehydrogenase (U/L) in the perfusate was significantly (p < .05) lower in the SUW group (429 +/- 58) as compared to ischemia-reperfusion (IR) (781 +/- 12) and the UW group (1151 +/- 83). Bile production (microg/min/g liver) was significantly (p < .05) higher in the SUW group (280 +/- 13) as compared to the IR (224 +/- 24) and the UW group (114 +/- 14). The tissue edema formation assessed by tissue wet-dry ratio was significantly (p < .05) higher in UW group. Histology showed well-preserved hepatic structure in the SUW group. In conclusion, this study suggests that HMP with SUW solution has the potential to restore and preserve livers with extended WIT.

Authors+Show Affiliations

Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18340625

Citation

Jain, Shailendra, et al. "Improved Preservation of Warm Ischemic Livers By Hypothermic Machine Perfusion With Supplemented University of Wisconsin Solution." Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research, vol. 21, no. 2, 2008, pp. 83-91.
Jain S, Lee SH, Korneszczuk K, et al. Improved preservation of warm ischemic livers by hypothermic machine perfusion with supplemented University of Wisconsin solution. J Invest Surg. 2008;21(2):83-91.
Jain, S., Lee, S. H., Korneszczuk, K., Culberson, C. R., Southard, J. H., Berthiaume, F., Zhang, J. X., Clemens, M. G., & Lee, C. Y. (2008). Improved preservation of warm ischemic livers by hypothermic machine perfusion with supplemented University of Wisconsin solution. Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research, 21(2), 83-91. https://doi.org/10.1080/08941930701883657
Jain S, et al. Improved Preservation of Warm Ischemic Livers By Hypothermic Machine Perfusion With Supplemented University of Wisconsin Solution. J Invest Surg. 2008 Mar-Apr;21(2):83-91. PubMed PMID: 18340625.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improved preservation of warm ischemic livers by hypothermic machine perfusion with supplemented University of Wisconsin solution. AU - Jain,Shailendra, AU - Lee,Sang Ho, AU - Korneszczuk,Katarzyna, AU - Culberson,Catherine R, AU - Southard,James H, AU - Berthiaume,François, AU - Zhang,Jian X, AU - Clemens,Mark G, AU - Lee,Charles Y, PY - 2008/3/15/pubmed PY - 2008/6/27/medline PY - 2008/3/15/entrez SP - 83 EP - 91 JF - Journal of investigative surgery : the official journal of the Academy of Surgical Research JO - J Invest Surg VL - 21 IS - 2 N2 - Hypothermic machine perfusion (HMP) has the potential to improve recovery and preservation of Donation after Cardiac Death (DCD) livers, including uncontrolled DCD livers. However, current perfusion solutions lack the needed substrates to improve energy recovery and minimize hepatic injury, if warm ischemic time (WIT) is extended. This proof-of-concept study tested the hypothesis that the University of Wisconsin (UW) solution supplemented with anaplerotic substrates, calcium chloride, thromboxane A2 inhibitor, and antioxidants could improve HMP preservation and minimize reperfusion injury of warm ischemic livers. Preflushed rat livers subjected to 60 min WIT were preserved for 5 h with standard UW or supplemented UW (SUW) solution. Post preservation hepatic functions and viability were assessed during isolated perfusion with Krebs-Henseleit solution. Livers preserved with SUW showed significantly (p < .001) improved recovery of tissue ATP levels (micromol/g liver), 2.06 +/- 0.10 (mean +/- SE), as compared to the UW group, 0.70 +/- 0.10, and the level was 80% of that of fresh control livers (2.60 +/- 0.13). At the end of 1 h of rewarming, lactate dehydrogenase (U/L) in the perfusate was significantly (p < .05) lower in the SUW group (429 +/- 58) as compared to ischemia-reperfusion (IR) (781 +/- 12) and the UW group (1151 +/- 83). Bile production (microg/min/g liver) was significantly (p < .05) higher in the SUW group (280 +/- 13) as compared to the IR (224 +/- 24) and the UW group (114 +/- 14). The tissue edema formation assessed by tissue wet-dry ratio was significantly (p < .05) higher in UW group. Histology showed well-preserved hepatic structure in the SUW group. In conclusion, this study suggests that HMP with SUW solution has the potential to restore and preserve livers with extended WIT. SN - 0894-1939 UR - https://www.unboundmedicine.com/medline/citation/18340625/Improved_preservation_of_warm_ischemic_livers_by_hypothermic_machine_perfusion_with_supplemented_University_of_Wisconsin_solution_ L2 - http://www.tandfonline.com/doi/full/10.1080/08941930701883657 DB - PRIME DP - Unbound Medicine ER -