Zonal heterogeneity of hepatic injury following shock/resuscitation: relationship of xanthine oxidase activity to localization of neutrophil accumulation and central lobular necrosis.
Post-ischemic hepatic injury is characterized by zonal heterogeneity of injury (central lobular necrosis), sinusoidal neutrophil accumulation, and injury generated by reactive oxygen metabolites. We evaluated the role of the heterogeneous distribution of hepatic xanthine oxidase in the generation of neutrophil accumulation and consequent hepatocellular injury in rats subjected to shock [controlled hemorrhagic hypotension (mean arterial pressure = 37.5 + or - 2.5 mmHg for 120 min)], with or without subsequent resuscitation and hemodynamic stabilization, compared with sham-operated rats. Shock/resuscitation produced striking neutrophil accumulation (assayed by esterase histochemistry) in the pericentral sinusoids, associated with centrolobular necrosis. This paralleled the pericentral distribution of xanthine oxidase (determined by histochemical assay of frozen sections) and its release from the liver into the circulation at resuscitation. Pretreatment with allopurinol inhibited hepatic xanthine oxidase activity, neutrophil accumulation, and pericentral hepatocyte necrosis in shock/resuscitation in rats. These findings suggest that reactive oxygen metabolites generated by heterogeneously distributed xanthine oxidase may contribute to the heterogeneity of hepatocellular injury in "ischemic hepatitis."
Mayumi
T
T
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-4685, USA.
Chan
C K
CK
Clemens
M G
MG
Bulkley
G B
GB
D000818:Animals; D002465:Cell Movement; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009336:Necrosis; D018375:Neutrophil Activation; D009504:Neutrophils / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000201:enzymology / Q000473:pathology*; D014969:Xanthine Oxidase / Q000032:analysis / Q000378:metabolism*
D014969:Xanthine Oxidase