P-selectin blockade is beneficial after uncontrolled hemorrhagic shock.
OBJECTIVE
The selectins play an important role in the neutrophil-mediated injury after hemorrhagic shock and resuscitation. The aim of this study was to investigate the effect of P-selectin blockade after HS and resuscitation.


METHODS
Forty-eight Sprague-Dawley rats were subjected to controlled combined with uncontrolled HS and resuscitation. Rats were divided into three groups (n = 16/group): (1) sham, no HS; (2) control, HS + resuscitation + drug vehicle; (3) treated, HS + anti-P-selectin monoclonal antibody. Transaminase levels to measure hepatocellular injury, liver myeloperoxidase to assess neutrophil infiltration, and histology were analyzed and compared between groups. Survival was followed for 3 days and was compared statistically.


RESULTS
Survival significantly increased from 30% in the control group to 70% in the treated group. Hepatocellular and structural injury as well as neutrophil infiltration were significantly decreased in treated animals.


CONCLUSIONS
Blockade of P-selectin resulted in decreased hepatocellular injury and increased survival in our model of uncontrolled HS. Selectins may be important therapeutic targets for blockade in the treatment of HS.
Rivera-Chavez
F
F
Department of Surgery, Michigan State University, B424 Clinical Center, East Lansing 48824-1315, USA.
Toledo-Pereyra
L H
LH
Nora
D T
DT
Bachulis
B
B
Ilgenfritz
F
F
Dean
R E
RE
D000818:Animals; D000911:Antibodies, Monoclonal; D008099:Liver / Q000098:blood supply / Q000201:enzymology / Q000293:injuries* / Q000378:metabolism; D008111:Liver Function Tests; D019007:P-Selectin / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D019007:P-Selectin; D009195:Peroxidase