title: Split-liver procedure and inflammatory response: improvement by pharmacological preconditioning.
abstract: BACKGROUND
  Final outcome of split-liver (SL) transplantation is impaired due to an increased rate of vascular complications and primary non-function. Herein, we hypothesized that an in situ split-liver procedure induces an inflammatory response and a deterioration of graft quality. We further studied whether graft quality can be improved by pharmacologic preconditioning.
  
  
  METHODS
  SL-procedure was performed in rats. One group (SL-HPP; n = 8) was pretreated according to a defined protocol [Homburg preconditioning protocol (HPP)], including pentoxyphylline, glycine, deferoxamine, N-acetylcysteine, erythropoietin, melatonin, and simvastatin. A second SL group (SL-Con; n = 8) received NaCl. Untreated non-SL served as controls (Sham; n = 8). Cytokines release, leukocyte invasion, endothelial activation and liver morphology were studied directly after liver harvest and after 8 h cold storage. Lung tissue was studied to determine remote injury.
  
  
  RESULTS
  The SL-procedure induced an increase of TNF-α concentration, intercellular-adhesion-molecule 1 (ICAM-1) expression, leukocytic-tissue infiltration and vacuolization. This was associated with an increased number of apoptotic hepatocytes. HPP reduced TNF-α release, ICAM-1 expression, the number of infiltrated leukocytes, as well as hepatocellular vacuolization and apoptosis. In lung tissue, the SL-procedure caused an increased IL-1 and IL-6 concentration and leukocyte infiltration.
  
  
  CONCLUSIONS
  HPP was capable of abrogating cytokine-mediated leukocytic response. Pharmacologic preconditioning of liver donors prevents the SL procedure-mediated inflammatory response, resulting in an improved graft quality.
authors: Department of General, Vascular and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany.
authors: Maximilian
authors: M
authors: von Heesen
authors: Matthias
authors: M
authors: Hülser
authors: Katharina
authors: K
authors: Seibert
authors: Claudia
authors: C
authors: Scheuer
authors: Stefan
authors: S
authors: Dold
authors: Otto
authors: O
authors: Kollmar
authors: Mathias
authors: M
authors: Wagner
authors: Michael D
authors: MD
authors: Menger
authors: Martin K
authors: MK
authors: Schilling
authors: Mohammed Reza
authors: MR
authors: Moussavian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000097:blood; D003676:Deferoxamine / Q000008:administration & dosage / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000517:prevention & control*; D007962:Leukocytes / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000379:methods* / Q000473:pathology; D008297:Male; D023421:Models, Animal; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology; D011300:Preoperative Care / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D003676:Deferoxamine; D010431:Pentoxifylline; D005998:Glycine