Hepatic cryoablation-induced multisystem injury: Bioluminescent detection of NF-κB activation in a transgenic mouse model

Ruxanna T. Sadikot, L. James Wudel, Duco E. Jansen, Jacob P. Debelak, Fiona E. Yull, John W. Christonan, Timothy S. Blackwell, William C. Chapman

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38 Scopus citations


Hepatic injury from cryoablation has been associated with multisystem injury, including adult respiratory distress syndrome, renal insufficiency, and coagulopathy; but the responsible mechanisms have not been well defined. In the present study we investigated the role of the transcription factor NF-κB in the multiorgan inflammatory response to hepatic cryoablation utilizing a novel in vivo system for determining NF-κB activity. Using transgenic mice expressing photinus luciferase under the control of the 5′ IIIV-LTR (an NF-κB-dependent promoter), we measured luciferase activity in the liver, lungs, and kidneys as a marker for NF-κB activity. Luciferase production was determined by in vivo bioluminescence and by luciferase assays of tissue homogenates. After measurement of basal luciferase activity, mice were treated with 35% hepatic cryoablation or sham laparotomy and injected with luciferin (0.75 mg/mouse). Photon emission from the liver, lungs, and kidneys was measured at multiple time points. Hepatic cryoablation induced a significant increase in photon emission by the liver, lungs, and kidneys, which correlated with markedly increased luciferase activity measured from each organ after death. Lung lavage 4 hours after cryoablation showed neutrophilic lung inflammation with increased MIP-2 levels compared with sham surgery. These findings demonstrate that 35% hepatic cryoablation is associated with NF-κB activation in the remnant liver and multiple distant sites, and may be causally related to the multisystem injury that is seen after direct liver injury.

Original languageEnglish
Pages (from-to)264-270
Number of pages7
JournalJournal of Gastrointestinal Surgery
Issue number2
StatePublished - 2002


  • Hepatic cryoablation
  • Liver injury
  • Multisystem injury
  • NF-κB


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