title: Multidrug donor preconditioning prevents cold liver preservation and reperfusion injury.
abstract: OBJECTIVE
  Primary graft dysfunction still represents a major challenge in liver transplantation. We herein studied in an isolated rat liver perfusion model whether a multidrug donor preconditioning (MDDP) can not only reduce but also completely prevent cold ischemia-reperfusion injury.
  
  
  METHODS
  MDDP included curcumin, simvastatin, N-acetylcysteine, erythropoietin, pentoxyphylline, melatonin, glycine, and methylprednisolone. Postischemic reperfusion was performed after 24 h cold storage in histidine-tryptophan-ketoglutarate solution with 37°C Krebs Henseleit bicarbonate buffer.
  
  
  RESULTS
  Cold hepatic ischemia-reperfusion resulted in a massive K(+) release, protein loss, and aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase elevation. This was associated with increased malondialdehyde formation, enhanced tumor necrosis factor-alpha and interleukin-6 production, pronounced leukocytic tissue infiltration, and apoptotic cell death.
  
  
  CONCLUSIONS
  MDDP abolished the inflammation response and was capable of completely preventing the manifestation of parenchymal injury. Thus, MDDP potentiates the protective effects reported after single-drug donor preconditioning and may therefore be an interesting approach to improve the outcome in clinical liver transplantation.
authors.affiliation: Department of General, Vascular and Pediatric Surgery, University of Saarland, 66421 Homburg/Saar, Germany. mamal@gmx.de
authors.forename: Mohammed Reza
authors.initials: MR
authors.lastname: Moussavian
authors.forename: Claudia
authors.initials: C
authors.lastname: Scheuer
authors.forename: Michael
authors.initials: M
authors.lastname: Schmidt
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
authors.forename: Matthias
authors.initials: M
authors.lastname: Wagner
authors.forename: Maximilian
authors.initials: M
authors.lastname: von Heesen
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
mesh_terms: D000818:Animals; D050377:Cold Ischemia / Q000009:adverse effects*; D015925:Cryopreservation; D005260:Female; D008099:Liver / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*