title: Intestinal microcirculation and gut permeability in acute pancreatitis: early changes and therapeutic implications.
abstract: Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 c 0.06 vs. 1.98 +/-0.04 nl x min(-1) x cap(-1) [control]; P = NS), whereas mucosal (1.59 +/-0.03 vs. 2.28 +/-0.03 nl x min(-1) x cap((-1))[control]; P <0.01) and subserosal (2.47 +/-0.04 vs. 3.74 +/-0.05 nl x min(-1) x cap((-1))[control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 +/-0.03 vs. 1.98 +/-0.04 nl x min(-1) x cap(-1) [control]; P <0. 01) and colonic (mucosal: 0.59 +/-0.01 vs. 2.28 +/-0.03 nl x min(-1) x cap((-1))[control], P <0.01; subserosal: 1.96 +/-0.05 vs. 3.74 +/-0.05 nl x min(-1) x cap(-1) [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 +/-19 nmol x thr(-1) x cm(-2); mild pancreatitis: 158 +/-23 nmol x hr(-1) x cm(-2); severe pancreatitis: 181 +/-33 nmol x hr(-1) x cm(-2); P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation.
authors.affiliation: Department of Surgery, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany. hhotz@surgery.medsch.ucla.edu
authors.forename: H G
authors.initials: HG
authors.lastname: Hotz
authors.forename: T
authors.initials: T
authors.lastname: Foitzik
authors.forename: J
authors.initials: J
authors.lastname: Rohweder
authors.forename: J D
authors.initials: JD
authors.lastname: Schulzke
authors.forename: M
authors.initials: M
authors.lastname: Fromm
authors.forename: N S
authors.initials: NS
authors.lastname: Runkel
authors.forename: H J
authors.initials: HJ
authors.lastname: Buhr
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D018988:Bacterial Translocation; D002199:Capillary Permeability / Q000502:physiology; D002108:Ceruletide; D003106:Colon / Q000098:blood supply*; D006002:Glycodeoxycholic Acid; D006439:Hemodynamics; D008297:Male; D008833:Microcirculation; D010179:Pancreas / Q000098:blood supply*; D010195:Pancreatitis / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D019283:Pancreatitis, Acute Necrotizing / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014741:Video Recording
chemical_list: D006002:Glycodeoxycholic Acid; D002108:Ceruletide