Role of P-selectin in total hepatic ischemia and reperfusion.
BACKGROUND
Ischemia and reperfusion of the liver are associated with changes in the interaction of leukocyte-endothelium cells. The role of an adhesion molecule, P-selectin, is studied in ischemia and reperfusion injury of the liver.


METHODS
Total hepatic ischemia was produced in the rat for 90 minutes, using a portosystemic shunt. To determine the role of P-selectin in ischemia and reperfusion, a murine IgG1 monoclonal antibody to P-selectin (1 mg/kg) was used at different times (30 minutes before and at reperfusion and five minutes and 24 hours after reperfusion). Rats survived for seven days, and tests showing hepatic injury, myeloperoxidase in hepatic tissue, and histologic studies were analyzed at four hours postreperfusion.


RESULTS
Survival improved from 15 percent for the rats in the ischemia control group to 55 percent for those in the group receiving anti-P-selectin antibody given 30 minutes before reperfusion (p < 0.05). We observed an improved statistically significant difference in tests demonstrating hepatic injury, myeloperoxidase in hepatic tissue, and histologic studies in the treated and ischemia control groups. The other groups did not show consistent significant differences.


CONCLUSIONS
P-selectin has a significant role in ischemia and reperfusion injury of the liver. Early modulation of the interaction between P-selectin and its ligand decreased neutrophil adhesion and migration and consequently diminished damage to the liver.
Garcia-Criado
F J
FJ
Surgical Research Institute, Borgess Medical Center, Kalamazoo, MI 49001, USA.
Toledo-Pereyra
L H
LH
Lopez-Neblina
F
F
Phillips
M L
ML
Paez-Rollys
A
A
Misawa
K
K
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007074:Immunoglobulin G / Q000276:immunology; D007511:Ischemia / Q000201:enzymology / Q000401:mortality / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D019007:P-Selectin / Q000276:immunology / Q000502:physiology*; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000401:mortality / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D018709:Statistics, Nonparametric; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D019007:P-Selectin; D009195:Peroxidase