incubated for 4 h in a shaking water bath. ELISA was utilized for IL-8 measurements. Four known pathways of IL-8 release were explored with their respective inhibitors: NF-B pathway (NF-B activation inhibitor), JNK pathway (JNK inhibitor II), p38 kinase pathway (SB 220025), and ERK kinase pathway with (UO126). Paired t-test was utilized for comparisons. The table displays that concurrent inhibition of the NF-B pathway, the JNK pathway, the p38 pathway, and the ERK pathway resulted in almost complete inhibition of IL-8 release by explants of human adipose tissue over a 4-h incubation. IL-8 release was not completely inhibited by any one inhibitor. These data indicate that up regulation of IL-8 release observed in vitro of human visceral adipose tissue is due to at least three different known pathways that regulate IL-8 release. More importantly, IL-8 release is not activated by just one pathway. Further studies are needed to examine what acti- vates these pathways in adipose tissue. P81. Helium Pneumoperitoneum Specifically Alters Liver Function Tests. A.R. Aurora, MD, MSC, E.J. Hanly, MD, J.M. Fuentes, MD, M.R. Marohn, DO, M.A. Talamini, MD. The Johns Hopkins University. Abdominal surgery is now commonly accomplished laparoscopically using carbon dioxide (CO 2 ) insufflation. Increased intraabdominal pres- sure (IAP) decreases hepatic blood flow, portal vein pressure, and he- patic pH. Furthermore, CO 2 pneumoperitoneum worsens systemic aci- dosis. Liver function tests (LFTs) are often elevated following laparoscopic cholecystectomy albeit without any clinical significance. Helium (He) may be an alternative to CO 2 pneumoperitoneum. We examined effects of IAP and the potential benefits afforded by He pneumoperitoneum on hepatocellular toxicity. Fifty male Sprague- Dawley rats were randomized to anesthesia control, CO 2 pneumoperi- toneum at 4 mmHg, CO 2 pneumoperitoneum at 8 mmHg, CO 2 pneu- moperitoneum at 12 mmHg, and Helium pneumoperitoneum at 12 mmHg. Rats received pneumoperitoneum or control procedure for 30 min. Alkaline phosphatase (AlkPhos), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured at baseline, 2 h, and 24 h following pneumoperitoneum. Helium increased ALT and AST at 2 h compared to all other groups. By 24 h AST was elevated in all groups except the He group. These differences between He and all other groups were not seen in AlkPhos. CO 2 pneumoperitoneum did not cause a significant change in LFTs compared to control regardless of changes in IAP, at any time point. Helium pneumoperitoneum acutely increases AST and ALT without altering AlkPhos. These results imply that hep- atocellular function is altered by He without significantly influencing biliary function, thus suggesting a highly specific mechanism of action. Furthermore, CO 2 pneumoperitoneum does not cause hepatocellular damage in the acute postoperative period regardless of IAP. CRITICAL CARE/GASTROINTESTINAL SESSION: THE GI INJURY RESPONSE P82. Obesity and Insulin Resistance Increases Sensitivity to Sepsis-Induced Hepatotoxicity. J. Barbato, MD, T. Allan, MD, M. Overhaus, MD, A. Bauer, MD, E. Tzeng, MD, T. Billiar, MD. University of Pittsburgh. Introduction. Sepsis in the setting of obesity and insulin resis- tance is associated with increased morbidity and mortality. The liver is a key intermediary in sepsis through production of cytokines and the up regulation of the inducible nitric oxide synthase (iNOS). Based on the significant fatty changes that occur in obesity, we hypothesized that the liver would exhibit an altered response to endotoxin injection. Methods. The obese Zucker rat was utilized as an accepted model of obesity and insulin-resistance. Obese rats were injected intraperitoneally with 1 mg/kg LPS. Lean controls received either 1 (low dose) or 2 mg/kg (high dose). Serum and tissue samples were obtained at baseline, 4h, and 24 h following LPS administration to measure liver enzyme levels, histopathology, and inflammatory mediators. Results. Obese Zucker rats demonstrated exquisite sen- sitivity to LPS injection with 100% mortality at doses of 2.5, 5, and 10 mg/kg at 24 h compared to 0% in lean controls. AST and ALT were significantly elevated at 4 h in the obese animals (1687  541 IU/L and 713  170 IU/L, respectively, n  4/group) compared to the low-dose (796  733 and 265  150) and high-dose controls (571  349 and 272  134; P  0.05). Serum TNF levels at 4 h were similarly elevated to 587 pg/mL versus 271 and 211 in the low and high dose controls (P  0.05). LPS administration in obese rats also increased iNOS protein expression at 4 h (see Figure) and circulating NO levels compared to lean controls. Conclusions. These findings demonstrate an exaggerated innate immune response in obese rats and suggest that the fatty liver displays an exaggerated susceptibil- ity to injury during endotoxemia. P83. NOS Inhibitors Modulate LPS-Induced Gastric MMP and TIMP Production. E.K. Robinson, MD, J.W. Suliburk, MD, L. Chang, BS, Y. Cui, MD, D.W. Mercer, MD. The Univer- sity of Texas Health Science Center Houston. Introduction. Matrix metalloproteinases (MMPs) are zinc- endopeptidases that are closely modulated by their endogenous inhib- itors, the tissue inhibitors of metalloproteinases, or TIMPs. We have previously demonstrated that lipopolysaccharide (LPS) induces gastric MMPs and that these MMPs contribute to LPS-induced gastric injury. Prior studies in our laboratory have also shown that LPS increases gastric inducible nitric oxide synthase (iNOS), the inhibition of which ameliorated LPS induced gastric injury. While nitric oxide has been shown to modulate MMP production in cell lines, the effect of NOS inhibition on LPS-induced gastric MMP production is unknown. The purpose of these studies was to determine what effects selective and nonselective NOS inhibition had on LPS-induced gastric MMP and TIMP production. Methods. Sprague-Dawley rats were treated with L-NAME (5 mg/kg sc), a nonselective NOS inhibitor, 1400w (1 mg/kg ip), a selective iNOS inhibitor, or vehicle followed by saline or LPS (20 mg/kg ip). After 24 h the rats were sacrificed and the gastric mucosa was harvested for protein and RNA extraction. MMP-2, MMP-9, TIMP-1, and TIMP-2 production were assessed by Western analysis TABLE—ABSTRACT P81 Alk Phos ALT AST t = 0 t = 2h t = 24 h t = 0 t = 2h t = 24 h t = 0 t = 2h t = 24 h Control 200 193 219 42 42 48 74 78 137 CO 2 4 mmHg 217 189 198 34 30 35 73 78 118 CO 2 8 mmHg 278 268 319 41 39 40 76 82 115 CO 2 12 mmHg 221 215 248 44 42 44 78 90 138 He 12 mmHg 248 215 243 37 55 34 68 109 77 332 ASSOCIATION FOR ACADEMIC SURGERY—ABSTRACTS