gms | German Medical Science

127. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

20.04. - 23.04.2010, Berlin

Article

Send article

Graft preconditioning mit low-dose tacrolimus (FK506) and nitric oxide inhibitor aminoguanidine (AGH) reduces ischemia/reperfusion injury after liver transplantation in the rat

Meeting Abstract

Search Medline for

  • Edouard Matevossian - Klinikum Rechts der Isar der TU München, Chirurgische Klinik und Poliklinik, München, Deutschland
  • Dietrich Doll - Chirurgische Klinik, Klinikum rechts der Isar TU München, Chirurgische Klinik, München, Deutschland
  • Norbert Hüser - Chirurgische Klinik, Klinikum rechts der Isar TU München, Chirurgische Klinik, München, Deutschland
  • Volker Aßfalg - Klinikum rechts der Isar der TU-München, Chirurgische Klinik und Poliklinik, München, Deutschland
  • Stefan Thorban - Chirurgische Klinik, Klinikum rechts der Isar TU München, Chirurgische Klinik, München, Deutschland

Deutsche Gesellschaft für Chirurgie. 127. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 20.-23.04.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10dgch343

doi: 10.3205/10dgch343, urn:nbn:de:0183-10dgch3433

Published: May 17, 2010

© 2010 Matevossian et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Introduction: Ischemia/reperfusion (I/R) injury is a main cause of primary dysfunction or non-function after liver transplantation (LTx). The I/R inury is a multifactorial process that affects graft function after LTx. Recent evidence indicates that an increase in nitric oxide (NO) production after LTx is associated with I/R injury. The aim of this study was to demonstrate that low-dose FK506 in combination with aminoguanidien (AGH), wich leads to a reduction of NO levels, has a protective effect by reducing I/R associated injury after LTx.

Materials and methods: Fortyone DA-(RT1av1) rats served as donors and recipients for syngeneic orthotopic arterialised LTx in microsurgical technique with cold ischemia of 120 minutes and warm ischemia of 12 minutes. They were divided into 4 groups: controlls without pre-treatment (group I, n=6), pre-treatment with high-dose FK506 (group II, n=11), pre-treatment with AGH only (group III, n=13), and pre-tretment with low-dose FK506 (0.001 mg s.c./kg BW per day) in combination with AGH, 1% 3 mL/d in tap water staring for 3 days before hepatectomy (group IV, n=11). After LTx the laboratory parameters and liver biopsy were performed.

Results: The levels of transaminase (ALT) in groups I, II and III were significantly higher on day 3 after LTx compared to group IV (p=0.001, p=0.000). In group IV the I/R-associated liver necrosis rate was reduced significantly.

Conclusion: Our results demonstrated that a combined dual pharmacological pre-treatment (preconditioning, group IV) reduced I/R inury of the graft after LTx in a rat model. Understanding the combined pharmacological role of NO and immunosuppressant FK506 might lead to promising new strategies that could help to prolong time of organ storage and to reduce graft failure in transplantation surgery.