title: Hemorrhage-induced hepatic injury and hypoperfusion can be prevented by direct peritoneal resuscitation.
abstract: BACKGROUND
  Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes).
  
  
  METHODS
  Anesthetized rats were randomly assigned (n = 8/group): (1) sham (no HS); (2) HS (40% mean arterial pressure for 60 min) plus conventional i.v. fluid resuscitation (CR; shed blood + 2 volumes saline); (3) HS + CR + 30 mL intraperitoneal (IP) DPR; or (4) HS + CR + 30 mL IP saline. Hemodynamics and hepatic blood flow were measured for 2 h after CR completion. In duplicate animals, liver and splanchnic tissues were harvested for histopathology (blinded, graded), hepatocellular function (liver enzymes), and tissue edema (wet-dry ratio).
  
  
  RESULTS
  Group 2 decreased liver blood flow, caused liver injuries (focal to submassive necrosis, zones 2 and 3) and tissue edema, and elevated liver enzymes (alanine aminotransferase (ALT), 149 +/- 28 microg/mL and aspartate aminotransferase (AST), 234 +/- 24 microg/mL; p < 0.05) compared to group 1 (73 +/- 9 and 119 +/- 10 microg/mL, respectively). Minimal/no injuries were observed in group 3; enzymes were normalized (ALT 89 +/- 9 microg/mL and AST 150 +/- 17 microg/mL), and tissue edema was similar to sham.
  
  
  CONCLUSIONS
  CR from HS restored and maintained central hemodynamics but did not restore or maintain liver perfusion and was associated with significant hepatocellular injury and dysfunction. DPR added to conventional resuscitation (blood and crystalloid) restored and maintained liver perfusion, prevented hepatocellular injury and edema, and preserved liver function.
authors.affiliation: Department of Internal Medicine, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Hurt
authors.forename: El Rasheid
authors.initials: el R
authors.lastname: Zakaria
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Matheson
authors.forename: Mahoney E
authors.initials: ME
authors.lastname: Cobb
authors.forename: John R
authors.initials: JR
authors.lastname: Parker
authors.forename: R Neal
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D005690:Galactose / Q000378:metabolism; D006339:Heart Rate; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology* / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D009336:Necrosis; D010530:Peritoneal Dialysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000150:complications / Q000517:prevention & control* / Q000628:therapy; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000150:complications*; D014883:Water-Electrolyte Imbalance / Q000628:therapy
chemical_list: D005690:Galactose