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increased with splanchnic ischemia. No studies have been performed in patients in acute liver failure (ALF). Methods: 16 general ICU (GICU) patients with varied admission aetiologies (median 67y [range 34-88y], 6M:10F), 20 patients with ALF (median 35y [range 17-59y], 7M:13F) and 44 healthy volunteers (median 32y [range 20-45y], 31M:13F) underwent combined absorption/permeability tests. Volunteers had a single test, critically ill patients were tested on admission and every 2-5 days until death or discharge. 100ml of water was given containing 5g lactulose (L), lg L-rhanmose (R), 0.5g D-xylose and 0.2g 3-O-m-D-glucose followed by a 5 hour urine collection. Urinary excretion (% dose) of the sugars was measured by HPLC. The L/R ratio represents an index of intestinal permeability. Gastric tonometry (pHi) was performed at the time of intestinal permeability assessment and daily APACHE II and organ failure scores (OFS) were performed. Results: Healthy volunteers had a L/R ratio of 0.028 ± 0.013(SD). Both patient groups had a marked increase in the L/R ratio on admission (GICU: 0.42 ± 0.10, ALF: 0.47 ± 0.19) returning to normal over 16-20 days. The L/R ratio and APACHE II score correlated directly in patients with ALF (r=0.48, p < 0.001) and a stepwise increase in L/R was seen with increasing OFS (p=0.002). In GICU patients the L/R ratio bore no relationship with APACHE or OFS, but correlated inversely with the pHi (r=-0.53, p < 0.001). Non-survivors had a significantly higher admission L/R ratio compared to survivors on the GICU (p < 0.05). C o n c l u s i o n : Both GICU and ALF patients have profoundly increased intestinal permeability on admission decreasing gradually over 16-20 days. Both patient groups behave differently as in patients with ALF the permeability increases in association with the severity of disease while in GICU patients the permeability increases in association with splanchnic ischemia.

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SPLANCHNIC ISCHEMIA IS ASSOCIATED WITH INCREASED INTESTINAL PERMEABILITY, ENDOTOXEMIA AND BACrEREMIA IN GENERAL INTENSIVE CARE PATIENTS BUT NOT IN ACUTE LIVER FAILURE, SM Gabe l, M Patel 2, GK Grimble 2, GR Barclay 3, R Williams 4, I Bjamason 5 & DBA Silk 1. 1Dept Gastroenterology, Central Middlesex Hospital; 2Roehampton Institute SW15; 3SE Scotland Blood Transfusion Centre, EH1; '*Institute of Hepatology, University College WC1E; 5Dept Medicine, Kings College Hospital SE5

Splanchnic ischemia caused by cardiopulmonary bypass results in a reversible increase in intestinal permeability and in animals is associated with endotoxaemia. These associations have been poorly studied in the critically ill, including patients with acute liver failure (ALF). M e t h o d s : 16 general ICU patients (GICU) with varied admission aetiologies (6M:10F) and 20 patients with ALF (7M:13F) underwent combined absorption/permeability tests on admission, repeated every 2-5 days until death/discharge. 100ml of water was given intragastrically containing 5g lactulose (L), lg L-rhamnose (R), 0.5g D-xylose and 0.2g 3-O-m-D-glucose followed by a 5 hour urine collection. Urinary excretion (% dose) of the sugars was measured by HPLC. The L/R ratio represents an index of intestinal permeability. During each permeability test blood cultures were taken, plasma end•toxin, IgM and IgG end•toxin-core antibodies (End•CAb) were measured. The gastric intramucosal pH (pHi) was measured by tonometry. Daily APACHE II scores were performed. Results: In GICU patients the pHi was inversely related to the L/R ratio (r=-0.53, p < 0.001) and the endotoxin concentration (r=-0.57, p < 0.001). A direct relationship was seen between the L/R ratio and plasma endotoxin (r=0.62, p < 0.0001) with inverse relationships between L/R ratio and IgM EndoCAb (r=-0.26, p=0.03) and IgG EndoCAb (r=--0.24, p=0.04). These associations are not seen in patients with ALF who show a direct relationship between the L/R ratio and the APACHE II score (r=0.48, p < 0.001). In both patient groups bacteraemi was associated with a significantly increased L/R ratio (p < 0.05). C o n c l u s i o n : Splanchnic ischemia is associated with an increase in intestinal permeability .and endotoxaemia in GICU patients. This mechanism does not seem to be responsible for the permeability changes seen in ALF, which relates more to the severity of illness. This difference could be accounted for by the increased splanchnic blood flow seen in ALF. Bacteraemia is associated with an increased intestinal permeability in both patient groups.

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TWO HIT MODEL OF INTESTINAL ISCHEMIA-REPERFUSION: TIMING NOT SEVERITY OF THE SECOND HIT CAUSES GUT AND LUNG INJURY. C_M Gallagher, WC Conner, H Tavaf-Motamen, T Miner, T Shea-Donohue, Dept of Surgery, Walter Reed AMC, Washington DC, Depts of Medicine and Surgery, USUHS, Bethesda, MD

A two hit model of intestinal ischemia-reperfusion (IR) injury is a proposed model for multiple organ dysfunction. Evidence suggests the initial insult of intestinal IR injury primes the gut to cause a systemic inflammatory response after sustaining a subsequent second hit. Using the model presented below, we have previously shown that 30 min of SMA occlusion resulted in gut and lung injury at 2 and 4 hrs with healing by 6 and 8 hrs, respectively. AIM: to determine the importance of timing and severity of the second hit on the development of acute lung injury. METHODS: Under anesthesia 200-300 gm rats underwent 30 rain of SMA occlusion, the first hit, followed by either 6 or 24 hrs of reperfusion (IR). Rats at 6 hrs of reperfusion underwent a second hit

I n t e s t i n a l D i s o r d e r s A 3 7 1

of 10 min of SMA occlusion (10), and rats at 24 hrs of reperfusion underwent a second hit of 30 min of SMA occlusion (30). Rats were harvested 2 hrs after the second hit. Appropriate sham controls (S) were performed. Evan's blue, a vital dye which binds albumin, was given IV 1 hr before tissue harvest. Dye concentration was measured in serum and bronchoalveolar lavage (BAL). Segments of small intestine were harvested for LTB 4 production and for histologic evaluation. Mucosal injury (MI) - 0 (normal) to 5(severe), villus height in/1 m (VH), and intestinal PMN's (#/hpf) were assessed in Giemsa- stained sections (5~t). RESULTS: 10 min of ischemia alone caused no gut injury. However, 10 min of ischemia given as the second hit 6 hrs after reperfusion (IR-6 ° -4 10) caused gut and lung injury as evidenced by diminished VH, severe MI, and elevated PMN infiltration in the gut and by increased amounts of Evan's blue in the BAL (table 1). Ischemia for 30 min given as the second hit following 24 hrs of reperfusion (IR-24 ° -4 30) caused no gut or lung injury. BAL values were similar to sham controls. Gut PMN infiltration and LTB 4 levels, a measure of PMN activation, were increased in both two hit groups compared to sham controls.

table I S -6 ° --~ S S -6 ° --~ 10 I R -6 ° --¢. S

BAL 7.8 ± 1.2 5.3 ± 3.9 2.8 :t: 4.4 MI 0.3+0.1 1.1±0.5 1.3±0.3 PMN 8±1 12±3 21±2 VH 476 ± 30 367 ± 19 388 ± 40

I R -6 ° ~ 10 I R -24 ° ~ 30

33.8 ± 7.5* 6.6 ± 1.8t 4.3 ± 0.2dp 1.5 ± 0.4t 33 ± 2~ 36 ± 3.0 179 ± 23(~ 404 + 45t

*P < 0.05 vs S -6 ° --~ S, d~ p< 0.001 vs S -6 ° ~ S, ? p < 0.0l vs IR -6 ° ~ 1O, n = 6-8

CONCLUSIONS: Delivery of a non-injurious episode of ischemia produces gut and lung injury. This data suggest a period of vulnerability to injury while the gut heals from the first hit. Increased gut PMN infiltration and LTB 4 levels, measures of acute inflammation, do not correlate with the amount of gut or lung injury after sustaining the second hit. In a two hit model of intestinal IR injury, the timing rather than severity of the second hit determines gut and lung injury.

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PATIENTS WITH IRRITABLE BOWEL SYNDROME (IBS) HAVE A HIGH PREVALENCE OF ALLERGY. E.A. Galliani P. Ravagnan, M. Fenti, A. D'Odorico, D. Martines, R. D'Inc~, F. De Lazzari. Gastroenterology Dep., University of Padua, Italy.

B a c k g r o u n d : Patients suffering from gastroeintestinal disease tend to exclude many aliments from their diet in order to prevent unpleasant symptoms. An high prevalence of sensitization to food is reported in IBS patients, although up to now it has not established which IBS patients need an allergic diagnostic procedure. Aims:l) To verify the prevalence of sensitisation to food in 2 groups of patients with Inflammatory Bowel Diseases (IBD: n °. 136; M/F :78/58; mean age :40.4 yrs) or Irritable Bowel Syndrome (IBS: n°.129; M/F :31/98; mean age :39.3 yrs). 2) To determine a subgroups of IBS possibly linked to allergy. Methods: We studied subjects consecutively presented at our out-patients because of routine follow up for IBD in remission or IBS with chronic diarrhea (n.°40; M/F :10/30; mean age :37.1 yrs) or with suspected food allergy (n.°89; M/F :21/68; mean age :40 yrs). Patients were accurately investigated for specific food intolerance and past history of allergic disease and symptoms. Skin prick tests (SPT) were performed by prick-by prick method with fresh aliments and by prick method with commercial inhalant purified allergens. Serum specific IgE (RAST, Pharmacia, Uppsala, Sweden) were assayed to confirm the results obtained by SPT. Chi-square test was applied for statistical analysis. Results:

IBD IBS-d~rrhea ] ms-aner~ History of aHerly 47.8% 51.1% [ 83.8%

0.001 I o.oo, I

Prick Test +re 34.5% 34.8% I 64.6% • food * 6/47 * 3/15 I * 8/64 • inahalant • 31/47 * 6/15 • 34/64 • food/iaahalant * 10/47 • 6/15 * 22/64

0.002 pc I 0002 I

A good correlation was found between positivity obtained with SPT and specific IgE in sera (p < 0.001). No concordance was found between specific food intolerance complaints by patients and positivity of both SPT and RAST tests. Summary: The higher prevalence of a positive history for allergy and sensitization to food and inhalant allergens in IBS patients who do not have an altered intestinal barrier, suggests a possible role of immunoallergic mechanisms in a subgroup of these patients: An allergological screening needs to be inserted in diagnstic flow chart of IBS patients with a history of allergy.