title: Intestinal hypoperfusion contributes to gut barrier failure in severe acute pancreatitis.
abstract: Intestinal barrier failure and subsequent bacterial translocation have been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis. Splanchnic hypoperfusion and ischemia/reperfusion injury have been postulated as a cause of increased intestinal permeability. The urinary concentration of intestinal fatty acid binding protein (IFABP) has been shown to be a sensitive marker of intestinal ischemia, with increased levels being associated with ischemia/reperfusion. The aim of the current study was to assess the relationship between excretion of IFABP in urine, gut mucosal barrier failure (intestinal hyperpermeability and systemic exposure to endotoxemia), and clinical severity. Patients with a clinical and biochemical diagnosis of acute pancreatitis were studied within 72 hours of onset of pain. Polyethylene glycol probes of 3350 kDa and 400 kDa were administered enterally, and the ratio of the percentage of retrieval of each probe after renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine the IFABP concentration (IFABP-c) and total IFABP (IFABP-t) excreted over the 24-hour period, using an enzyme-linked immunosorbent assay technique. The systemic inflammatory response was estimated from peak 0 to 72-hour plasma C-reactive protein levels, and systemic exposure to endotoxins was measured using serum IgM endotoxin cytoplasmic antibody (EndoCAb) levels. The severity of the attack was assessed on the basis of the Atlanta criteria. Sixty-one patients with acute pancreatitis (severe in 19) and 12 healthy control subjects were studied. Compared to mild attacks, severe attacks were associated with significantly higher urinary IFABP-c (median 1092 pg/ml vs. 84 pg/ml; P < 0.001) and IFABP-t (median 1.14 microg vs. 0.21 microg; P = 0.003). Furthermore, the control group had significantly lower IFABP-c (median 37 pg/ml; P = 0.029) and IFABP-t (median 0.06 microg; P = 0.005) than patients with mild attacks. IFABP correlated positively with the polyethylene glycol 3350 percentage retrieval (r = 0.50; P < 0.001), CRP (r = 0.51; P < 0.001), and inversely with serum IgM EndoCAb levels (r = -0.32; P = 0.02). The results of this study support the hypothesis that splanchnic hypoperfusion contributes to the loss of intestinal mucosal integrity associated with a severe attack of pancreatitis.
authors.affiliation: Academic Department of Surgery, The General Infirmary at Leeds, Leeds.
authors.forename: Sakhawat H
authors.initials: SH
authors.lastname: Rahman
authors.affiliation: Academic Department of Surgery, The General Infirmary at Leeds, Leeds.
authors.forename: Basil J
authors.initials: BJ
authors.lastname: Ammori
authors.affiliation: Academic Department of Surgery, The General Infirmary at Leeds, Leeds.
authors.forename: John
authors.initials: J
authors.lastname: Holmfield
authors.affiliation: Postgraduate Medical School, University of Nottingham, Derby, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Larvin
authors.affiliation: Academic Department of Surgery, The General Infirmary at Leeds, Leeds.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McMahon
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis; D002352:Carrier Proteins / Q000652:urine*; D004731:Endotoxins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000652:urine*; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007422:Intestines / Q000098:blood supply* / Q000503:physiopathology*; D007511:Ischemia / Q000150:complications / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology / Q000503:physiopathology; D009363:Neoplasm Proteins; D010195:Pancreatitis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D010539:Permeability; D011092:Polyethylene Glycols; D025521:Tumor Suppressor Proteins
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D004731:Endotoxins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D007075:Immunoglobulin M; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; C042058:core endotoxin; D011092:Polyethylene Glycols; D002097:C-Reactive Protein