Multidrug donor preconditioning prevents cold liver preservation and reperfusion injury.

Abstract

PURPOSE:

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: Mohammed Reza Moussavian, Claudia Scheuer, Michael Schmidt, Otto Kollmar, Matthias Wagner, Maximilian von Heesen, Martin K Schilling, Michael D Menger
• Journal: Langenbeck's archives of surgery (Langenbecks Arch Surg) Vol. 396 Issue 2 Pg. 231-41 (Feb 2011) ISSN: 1435-2451 [Electronic] Germany
• PMID: 20582598 (Publication Type: Journal Article)

Topics

• Animals
• Cold Ischemia (adverse effects)
• Cryopreservation
• Female
• Liver (drug effects)
• Male
• Models, Animal
• Organ Preservation (methods)
• Perfusion
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (etiology, prevention & control)