Graft preconditioning with low-dose tacrolimus (FK506) and nitric oxide inhibitor aminoguanidine (AGH) reduces ischemia/reperfusion injury after liver transplantation in the rat.
Ischemia/reperfusion (I/R) injury is a main cause of primary dysfunction or non-function after liver transplantation (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 aminoguanidine (AGH), which leads to a reduction of NO levels, has a protective effect by reducing I/R associated injury after LTx. Fortyone DA-(RT1av1) rats served as donors and recipients for syngenic orthotopic arterialised LTx. They were divided into 4 groups: controls without pre-/treatment (I), pre-/treatment with high-dose FK506 (II), pre-/treatment with AGH only (III), and pre-/treatment with low-dose FK506 in combination with AGH (IV). After LTx the laboratory parameters and liver biopsy were performed. 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 = 0.001, p = 0.000). In group IV the I/R-associated liver necrosis rate was reduced significantly. Our results demonstrated that a combined dual pharmacological pretreatment (group IV) reduced I/R injury of the graft after LTx in a rat model.
Hüser
Norbert
N
Department of Surgery, Technische Universität München, München, Germany.
Doll
Dietrich
D
Altomonte
Jennifer
J
Werner
Martin
M
Kriner
Monika
M
Preissel
Anne
A
Thorban
Stefan
S
Matevossian
Edouard
E
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D016031:Liver Transplantation; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000517:prevention & control*; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*
D006146:Guanidines; D009569:Nitric Oxide; C004479:pimagedine; D016559:Tacrolimus