Fiona Yull

Last active: 3/21/2018

Hepatic cryoablation-induced multisystem injury: bioluminescent detection of NF-kappaB activation in a transgenic mouse model.

Sadikot RT, Wudel LJ, Jansen DE, Debelak JP, Yull FE, Christman JW, Blackwell TS, Chapman WC
J Gastrointest Surg. 2002 6 (2): 264-70

PMID: 11992813

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-kappaB in the multiorgan inflammatory response to hepatic cryoablation utilizing a novel in vivo system for determining NF-kappaB activity. Using transgenic mice expressing photinus luciferase under the control of the 5' HIV-LTR (an NF-kappaB-dependent promoter), we measured luciferase activity in the liver, lungs, and kidneys as a marker for NF-kappaB 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-kappaB 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.

MeSH Terms (14)

Animals Cryosurgery Disease Models, Animal Enzyme-Linked Immunosorbent Assay Kidney Liver Luminescent Measurements Lung Mice Mice, Transgenic Multiple Organ Failure NF-kappa B Risk Assessment Sensitivity and Specificity

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