title: Pancreatic duct ligation reduces lung injury following trauma and hemorrhagic shock.
abstract: OBJECTIVE
  To determine whether pancreatic digestive enzymes released into the ischemic gut during an episode of T/HS are involved in the generation of distant organ injury. This hypothesis was tested by examining the effect of PDL on T/HS-induced intestinal injury, lung injury, and RBC deformability.
  
  
  BACKGROUND
  The effect of pancreatic duct ligation (PDL) on distant organ injury following trauma/hemorrhagic shock (T/HS) was examined. PDL before T/HS decreases lung and red blood cell (RBC) injury and exerts a limited protective effect on the gut. Pancreatic proteases in the ischemic gut appear to be involved in gut-induced lung and RBC injury. Based on recent work, it appears that proinflammatory and/or toxic factors, which are generated by the ischemic intestine, play an important role in the pathogenesis of multiple organ failure. The process by which these toxic factors are generated remains unknown. Previous experimental work has clearly documented that intraluminal inhibition of pancreatic proteases decreases the degree of T/HS-induced lung injury and neutrophil activation. One possible explanation for this observation is that the toxic factors present in intestinal lymph are byproducts of interactions between pancreatic proteases and the ischemic gut.
  
  
  METHODS
  Male Sprague-Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of sham (T/SS) or T/HS with or without PDL. At 3 and 24 hours following resuscitation, animals were killed and samples of gut, lung, and blood were collected for analysis. Lung permeability, pulmonary myeloperoxidase levels, and bronchoalveolar fluid protein content were used to quantitate lung injury. Intestinal injury was determined by histologic analysis of terminal ileum (% villi injured). To assess RBC injury, RBC deformability was measured, as the RBC elongation index (RBC-EI), using a LORCA device.
  
  
  RESULTS
  At 3 and 24 hours following resuscitation, PDL prevented shock-induced increases in lung permeability to both Evans blue dye and protein in addition to preventing an increase in pulmonary myeloperoxidase levels. T/HS-induced impairments in RBC deformability were significantly reduced at both time points in the PDL + T/HS group, but deformability did not return to T/SS levels. PDL did reduce the magnitude of ileal injury at 3 hours after T/HS, but the protective effect was lost at 24 hours after T/HS.
  
  
  CONCLUSIONS
  PDL prior to T/HS decreases lung injury and improves RBC deformability but exerts a limited protective effect on the gut. Thus, the presence of pancreatic digestive enzymes in the ischemic gut appears to be involved in gut-induced lung and RBC injury.
authors.affiliation: Department of Surgery, University of Medicine, and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Cohen
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Magnotti
authors.forename: Qi
authors.initials: Q
authors.lastname: Lu
authors.forename: Da Zhong
authors.initials: DZ
authors.lastname: Xu
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Berezina
authors.forename: Sergey B
authors.initials: SB
authors.lastname: Zaets
authors.forename: Carlos
authors.initials: C
authors.lastname: Alvarez
authors.forename: George
authors.initials: G
authors.lastname: Machiedo
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D004396:Coloring Agents; D004907:Erythrocyte Deformability; D005070:Evans Blue; D007082:Ileum / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D008026:Ligation; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010179:Pancreas / Q000201:enzymology; D010183:Pancreatic Ducts / Q000601:surgery*; D010189:Pancreatic Juice / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications / Q000473:pathology / Q000503:physiopathology*
chemical_list: D004396:Coloring Agents; D005070:Evans Blue