Method of direct segmental intra-hepatic delivery using a rat liver hilar clamp model

Eliza W. Beal, Curtis Dumond, Jung Lye Kim, Khalid Mumtaz, Don Hayes, Ken Washburn, Bryan A. Whitson, Sylvester M. Black

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ischemia/reperfusion (I/R) injury with myriad negative consequences. Potential I/R injury in marginal organs destined for liver transplantation contributes to the current donor shortage secondary to a decreased organ utilization rate. A significant need exists to explore hepatic I/R injury in order to mediate its impact on graft function in transplantation. Rat liver hilar clamp models are used to investigate the impact of different molecules on hepatic I/R injury. Depending on the model, these molecules have been delivered using inhalation, epidural infusion, intraperitoneal injection, intravenous administration or injection into the peripheral superior mesenteric vein. A rat liver hilar clamp model has been developed for use in studying the impact of pharmacologic molecules in ameliorating I/R injury. The described model for rat liver hilar clamp includes direct cannulation of the portal supply to the ischemic hepatic segment via a side branch of the portal vein, allowing for direct segmental hepatic delivery. Our approach is to induce ischemia in the left lateral and median lobes for 60 min, during which time the substance under study is infused. In this case, pegylated-superoxide dismutase (PEG-SOD), a free radical scavenger, is infused directly into the ischemic segment. This series of experiments demonstrates that infusion of PEG-SOD is protective against hepatic I/R injury. Advantages of this approach include direct injection of the molecule into the ischemic segment with consequent decrease in volume of distribution and reduction in systemic side effects.

Original languageEnglish (US)
Article numbere54729
JournalJournal of Visualized Experiments
Volume2017
Issue number122
DOIs
StatePublished - Apr 2 2017

Keywords

  • Direct cannulation
  • Hepatic delivery
  • Hilar clamp
  • Ischemia-reperfusion injury
  • Issue 122
  • Liver transplantation
  • Medicine
  • Polyethylene glycol-superoxide dismutase (PEG-SOD)
  • Rat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Beal, E. W., Dumond, C., Kim, J. L., Mumtaz, K., Hayes, D., Washburn, K., Whitson, B. A., & Black, S. M. (2017). Method of direct segmental intra-hepatic delivery using a rat liver hilar clamp model. Journal of Visualized Experiments, 2017(122), [e54729]. https://doi.org/10.3791/54729