Abstracts
2000 Digestive Disease Week

# 2267 Hepatic Protection in E. Coli Septic Shock as Well as Hemorrhagic Shock by MMPI Inhibition.
Alberto S. Santibanez-Gallerani, Annabelle Barber, George Thomas Shires, Shelly J. Williams, Peter J. Mazolewski, Jeff Avansino, Brett Murray, Shawn Davis, Yan Zhao, Las Vegas, NV

Cytokines such as TNF-a and IL-6 are elevated in hemorrhagic shock. Experimental models of septic shock have produced controversial results and a lack of clinical correlation. Recently, Matrix Metalloproteinase Inhibitors (MMPI) have been observed to decrease TNF-a via inhibition of TNF-a convertase. MMPI has recently been shown to offer hepatic protection in hemorrhagic shock. The purpose of this study was to investigate the effects of MMPI in vivo on the levels of TNF-a and IL-6 when exposed to Escherichia coli induced septic shock as compared to hemorrhagic shock (HS) produced by 35% blood volume reduction. Sprague- Dawley rats (n=24)(300-400 grams) were divided into: HS, E. coli sepsis (ATCC 25922, 4.5 x 107 CFU), and with and without the administration of MMPI (2.5 µg/kg British Biotech 1101). MMPI was administered 15 minutes post shock. Hepatic membrane potentials (Em) and hepatic blood flows were measured at baseline, at 90, and 180 minutes. Carotid arterial blood samples were analyzed for IL-6 and TNF-a. Student T-test statistical analysis was performed. It is concluded that MMPI has a protective effect on hepatic integrity as demonstrated by a stabilization of the membrane potential in both forms of shock. This stabilization is independent of the mean arterial pressure and hepatic blood flow and is most likely the result of the inhibition of the TNF-a cascade. Interestingly, IL-6 levels were influenced differently depending on the type of shock; thus, suggesting two independent pathways of induction, and possibly accounting for the differences in clinical correlation.