Carbon monoxide inhalation ameliorates cold ischemia/reperfusion injury after rat liver transplantation

Surgery. 2005 Aug;138(2):229-35. doi: 10.1016/j.surg.2005.06.015.


Background: Carbon monoxide (CO), a product of heme degradation by heme oxygenase, induces cytoprotection against ischemia/reperfusion (I/R) injury in a variety of organs such as the heart, lung, kidney, and small intestine. We examined whether CO would protect liver grafts against cold I/R injury associated with transplantation.

Methods: Orthotopic liver transplantation (OLT) was performed in syngeneic Lewis rats with 18 hours preservation in cold University of Wisconsin solution. Recipients were exposed to air or CO (100 ppm) for 1 hour before and 24 hours after OLT. Recipients were sacrificed 0.5 to 48 hours post-transplant.

Results: CO inhalation significantly decreased serum aspartate aminotransferase and alanine aminotransferase levels and suppressed hepatic necrosis formation and neutrophil accumulation at 6 to 48 hours after OLT, compared with air control. The expressions of tumor necrosis factor alpha, intercellular adhesion molecule 1, and inducible nitric oxide synthase messenger RNA in the liver graft were significantly inhibited in the CO-treated group at 1 hour after reperfusion. Hepatic nuclear factor-kappaB activation did not differ between the groups.

Conclusions: The results demonstrate that exogenous CO treatment suppresses early proinflammatory gene expression and neutrophil infiltration, and efficiently ameliorates hepatic I/R injury. The possible mechanism by which CO protects the liver against cold I/R does not seem to be associated with downregulation of the nuclear factor-kappaB-signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Animals
  • Carbon Monoxide / blood
  • Carbon Monoxide / pharmacology*
  • Cryopreservation*
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Hemoglobins / metabolism
  • Intercellular Adhesion Molecule-1 / genetics
  • Liver Transplantation*
  • Male
  • NF-kappa B / metabolism
  • Neutrophils / drug effects
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type II
  • Rats
  • Rats, Inbred Lew
  • Reperfusion Injury / drug therapy*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / genetics


  • Hemoglobins
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Carbon Monoxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat