Effects of dextran and pentoxifylline on hemorrhagic shock-induced P-selectin expression.
BACKGROUND
Dextran and pentoxifylline have been shown to prevent leukocyte-endothelium adherence encountered after hemorrhagic shock. P-Selectin is the first endothelial cell adhesion molecule to be upregulated after an ischemic insult. We investigated the effects of resuscitation with dextran 70 and administration of pentoxifylline during resuscitation on hemorrhagic shock-induced P-selectin expression.


METHODS
Hemorrhagic shock was induced in C57BL/6 mice by withdrawing blood to reduce mean arterial blood pressure to 30 mm Hg for 45 min. Animals were resuscitated by infusing one of the following solutions (each n:5): (1) Ringer's lactate, (2) 6% dextran 70, (3) Ringer's lactate plus 50 mg/kg pentoxifylline, (4) 5% human albumin. Afterward shed blood was infused. In vivo P-selectin expression was determined using dual-radiolabeled monoclonal antibody technique in lung, heart, liver, kidney, mesentery, stomach, small bowel, and colon 5 h after resuscitation.


RESULTS
P-Selectin was significantly upregulated in all of the organs studied in the Ringer's lactate resuscitation group (P < 0.001). Resuscitation with dextran 70 and administration of pentoxifylline during resuscitation prevented P-selectin upregulation. Resuscitation with human albumin caused significant attenuation but could not prevent P-selectin upregulation (p < 0.01).


CONCLUSIONS
Our study implies that the prevention of hemorrhagic shock-induced leukocyte-endothelium adherence by dextran 70 and pentoxifylline observed in other studies may be mediated by prevention of P-selectin expression by these agents.
Akgür
F M
FM
School of Medicine, Dokuz Eylül University, Izmir, Turkey. gzibari@lsumc.edu
Zibari
G B
GB
McDonald
J C
JC
Granger
D N
DN
Brown
M F
MF
D000818:Animals; D003911:Dextrans / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000096:biosynthesis*; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D015854:Up-Regulation
D003911:Dextrans; D019007:P-Selectin; D010431:Pentoxifylline