Sialyl Lewis (x) analog improves liver function by decreasing neutrophil migration after hemorrhagic shock
Rubio-Avilla, J.; Palma-Vargas, J.M.; Collins, J.T.; Smejkal, R.; McLaren, J.; Phillips, L.M.; Toledo-Pereyra, L.H.
Journal of Trauma 43(2): 313-318
1997
ISSN/ISBN: 0022-5282 PMID: 9291378 Document Number: 480163
Background: Little is known about the changes in the hepatic microcirculation and the leukocyte-endothelial adhesion processes during the early reperfusion period after resuscitation in hemorrhagic shock. P-selectin and its natural ligand Sialyl Lewis-x (SLe-x) are involved in the early stages of reperfusion events leading to neutrophil migration. Therefore, the aim of this study was to investigate the effect of the administration of CY-1747, a synthetic SLe-x analog, in the liver inflammatory response and neutrophil migration after hemorrhagic shock. Materials and Methods: Rats, each weighing 275 to 300 grams, were subjected to 60 minutes of pressure controlled hemorrhagic shock. After this period, animals were resuscitated according to the following protocol: shed blood was reinfused to equal 50% of the total volume bled, and the other 50% was replaced with 3 times volume of Ringer's lactated solution. Animals were divided into sham and two study groups to receive vehicle (controls) and CY-1747 (10 mg/kg intravenously) diluted in 1 mL of normal saline 45 minutes after initiating hemorrhagic shock. The following parameters were analyzed: 7-day survival, liver injury tests, liver tissue myeloperoxidase as an index of neutrophil infiltration, and liver histology. Results: Survival was significantly increased from 48% in the controls to 90% in the CY-1747 treated group. Animals treated with the SLe-x analog showed significantly better mean arterial blood pressure after 15 minutes after resuscitation. Also, the treated group showed a marked decrease in liver enzymes levels at 5 minutes and 4 hours after reperfusion. Neutrophil migration was significantly ameliorated as reflected by decreased myeloperoxidase levels in the SLe-x analog treated group. Furthermore, we observed improved histologic damage scores in the treated group when compared with controls. Conclusions: The SLe-x analog, CY-1747, had a protective effect in ischemic livers by decreasing neutrophil migration after hemorrhagic shock and resuscitation. This protective effect also resulted in improved survival and mean arterial blood pressure after resuscitation.