Acute lung injury after hepatic cryoablation: correlation with NF-kappa B activation and cytokine production

Surgery. 1999 Sep;126(3):518-26.


Background: Previous clinical reports have documented multisystem organ injury after hepatic cryoablation. We hypothesized that hepatic cryosurgery, but not partial hepatectomy, induces a systemic inflammatory response characterized by distant organ injury and overproduction of nuclear factor kappa B (NF-kappa B)-dependent, proinflammatory cytokines.

Methods: In this study, rats underwent either cryoablation of 35% of liver parenchyma or a similar resection of left hepatic tissue. Serum tumor necrosis factor-alpha and macrophage inflammatory protein-2 levels and NF-kappa B activation were assessed by electrophoretic mobility shift assay at 30 minutes 1, 2, 6, and 24 hours after either procedure.

Results: Cryoablation of 35% of liver (n = 22 rats) resulted in lung injury and a 45% mortality rate within 24 hours of surgery, whereas 7% treated with 35% hepatectomy (n = 15 rats) died during the 24 hours after surgery (P < .05, cryoablation vs hepatectomy). Serum tumor necrosis factor-alpha and macrophage inflammatory protein-2 levels were markedly increased in rats (n = 10 rats) 1 hour after hepatic cryoablation compared with rats that underwent partial hepatectomy (P < .005). We evaluated NF-kappa B activation by electrophoretic mobility shift assay in nuclear extracts of liver and lung after cryosurgery and found that NF-kappa B activation was strikingly increased in the liver but not the lung at 30 minutes and in both organs 1 hour after cryosurgery, and returned to baseline in both organs by 2 hours. In rats undergoing 35% hepatectomy, no increase in NF-kappa B activation was detected in nuclear extracts of either liver or lung at any time point.

Conclusions: These data show that hepatic cryosurgery results in systemic inflammation with activation of NF-kappa B and increased production of NF-kappa B-dependent cytokines. Our data suggest that lung injury and death in this animal model is mediated by an exaggerated inflammatory response to cryosurgery.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Chemokine CXCL2
  • Cryosurgery / adverse effects*
  • Cytokines / biosynthesis*
  • Disease Models, Animal
  • Hepatectomy / adverse effects
  • Humans
  • Inflammation Mediators / metabolism
  • Liver / metabolism
  • Liver / surgery*
  • Lung / metabolism
  • Lung / pathology
  • Lung Injury*
  • Monokines / blood
  • NF-kappa B / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism


  • Chemokine CXCL2
  • Cytokines
  • Inflammation Mediators
  • Monokines
  • NF-kappa B
  • Tumor Necrosis Factor-alpha