Hepatic neutrophil activation during reperfusion may not contribute to initial graft function after short cold ischemia in human liver transplantation

Transplant Proc. 2009 Mar;41(2):739-42. doi: 10.1016/j.transproceed.2009.01.034.

Abstract

Background: Experimental models of hepatic ischemia/reperfusion injury have implicated a pathophysiologic role for neutrophils in subsequent hepatocellular damage. In human liver transplantation, however, the effect of reperfusion-induced neutrophil activation on initial graft function is not clear.

Methods: In 38 patients undergoing liver transplantation, neutrophil CD11b and L-selectin expression, neutrophil count, and plasma lactoferrin levels were measured. To assess changes within the graft during initial reperfusion, samples of blood entering and leaving the graft were obtained simultaneously, and transhepatic ratio calculated (hepatic vein/portal vein; 1 denotes no change, <1 a decrease, and >1 an increase across the liver). Graft steatosis, postoperative liver function, and outcome were recorded. Associations between neutrophil activation markers and outcome measures were evaluated.

Results: Substantial hepatic neutrophil activation occurred during initial reperfusion, demonstrated by concomitant L-selectin shedding and CD11b upregulation (transhepatic ratios 0.9 [0.7-1.0]; 1.4 [0.9-1.9]; both P < .001; portal vs hepatic vein]. Simultaneously, hepatic neutrophil sequestration and lactoferrin release occurred (0.3 [0.2-0.5]; 1.7 [1.3-3.4]; both P < .001). Neither cold ischemic time (CIT; median 5 hours 36 minutes) nor hepatic neutrophil activation during reperfusion predicted early graft function, nor was there any association between CIT and neutrophil activation.

Conclusions: Despite short CIT, extensive graft neutrophil activation and sequestration occurred. This, however, was not associated with impaired early graft function, suggesting short CIT may protect against severe neutrophil-mediated injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / blood
  • CD11b Antigen / blood
  • Female
  • Graft Rejection / epidemiology
  • Graft Survival / physiology
  • Hepatic Veins / physiology
  • Humans
  • Ischemia
  • L-Selectin / metabolism
  • Lactoferrin / blood
  • Leukocyte Count
  • Liver Diseases / classification
  • Liver Diseases / surgery
  • Liver Transplantation / immunology
  • Liver Transplantation / mortality
  • Liver Transplantation / physiology*
  • Male
  • Middle Aged
  • Neutrophil Activation / physiology*
  • Portal Vein / physiology
  • Reperfusion*
  • Survival Analysis
  • Survivors
  • Young Adult

Substances

  • Antigens, CD
  • CD11b Antigen
  • L-Selectin
  • Lactoferrin