Abstracts
1999 Digestive Disease Week

# 2123 THE ROLE OF INTRAOPERATIVE ULTRASOUND IN THE DETECTION OF OCCULT LIVER METASTASES AFTER HELICAL CT STAGING IN RESECTABLE PANCREATIC AND PERIAMPULLARY ADENOCARCINOMA
A S Santibanez-Gallerani, A Barber, S J Williams, S Davis, Y Zhao, G Tom Shires, Univ of Nevada Sch of Medicine, Las Vegas, NV

Hemorrhagic shock increases cytokines, such as Tumor Necrosis Factor (TNF-a), and compromises hepatic function and integrity. The production of TNF-a involves a cascade reaction regulated by the enzyme TNF-a convertase. The purpose of this study was to examine the effects of Matrix Metalloproteinase Inhibitor (MMPI) (British Biotech 1101) in vivo on hepatic integrity in a rat model exposed to 35% hemorrhagic shock (HS). Sprague-Dawley rats (n = 10) (300-350 grams) were divided into: hemorrhagic shock (HS) and HS + MMPI. MMPI (2.5 mg/kg) was administered intraperitoneally 15 minutes post induction of shock. TNF-a levels were collected at baseline and at 90 minutes post induction of shock from the carotid artery, suprahepatic IVC, portal vein and suprarenal IVC. Membrane potentials (Em) of the hepatic membrane and hepatic flows were also obtained at baseline, and at 90 minutes in order to assess hepatic integrity. Student T-test statistical analysis was performed. In hemorrhagic shock, the administration of MMPI decreased TNF-a levels (p<0.05). Further, MMPI stabilized the membrane potential at -30 mV as compared to the depolarized membrane potential at -22 mV for HS without MMPI. TNF-a was significantly higher in the portal and hepatic circulations as compared to the systemic circulation in rats exposed to hemorrhagic shock. These changes were not observed in the groups treated with MMPI. In conclusion, this study demonstrates that MMPI decreases TNF-a levels and protects hepatic integrity in hemorrhagic shock as evidenced by the stablization of the membrane potential, independent of the MAP and hepatic blood flow. The hepatic protection is closely related to the decrease in TNF-a levels seen in the portal circulation produced from bowel. The mechanism of action of the protective effect of MMPI may be due to the inhibition of the TNF-a convertase enzyme. This inhibition may prevent the escalation of the cytokine cascade induced by hemorrhagic shock.

Group	MAP	Flow	Em	TNF-a
	(mmHg)	(ml/min/100gm)	(mV)	(pg/ml)
	Pre/Post	Pre/Post	Pre/Post	Pre/Post
HS	117/34*	73/27*	-30/-22*	<15/600*
HS+MMPI	118/26*	67/34*	-30/-30	<15/170*
*p<0.05

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