Multidrug donor preconditioning prevents cold liver preservation and reperfusion injury.
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.
Moussavian
Mohammed Reza
MR
Department of General, Vascular and Pediatric Surgery, University of Saarland, 66421 Homburg/Saar, Germany. mamal@gmx.de
Scheuer
Claudia
C
Schmidt
Michael
M
Kollmar
Otto
O
Wagner
Matthias
M
von Heesen
Maximilian
M
Schilling
Martin K
MK
Menger
Michael D
MD
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*