The effect of normothermic recirculation is mediated by ischemic preconditioning in NHBD liver transplantation.
We have evaluated the involvement of hepatic preconditioning mediators (adenosine, adenosine A1 and A2 receptors) during normothermic recirculation (NR) in a model of liver transplantation from non-heart-beating donor (NHBD) pigs. Application of NR after 20 min of warm ischemia (WI) reversed the lethal injury associated with transplantation of NHBD livers (achieving 5-day survival and diminishing glutathione S-transferase (GST), aspartate aminotransferase (AST) and hyaluronic acid (HA)). Adenosine administration prior to WI simulated the effect of NR. Measuring adenosine, we found that during NR, hepatic adenosine levels increased and xanthine levels decreased. Then when we blocked A2 receptors the effect of NR was abolished, whereas the blocking of A1 receptors further protected the liver. Furthermore, A2 blocking improved hepatic perfusion during NR whereas A1 blocking reduced it. The study suggests that NR has a preconditioning effect by maintaining adequate adenosine and xanthine levels. During NR, adenosine protects the liver through A2 activation and damages it through A1 activation although simultaneous stimulation of both receptors exerts a clear beneficial effect. The possible relation of NR mechanism with other preconditioning mediators such as cAMP and nitric oxide synthesis are discussed.
Net
Marc
M
Transplant Coordination, Hospital Clinic de Barcelona, Universitat de Barcelona, Villarroel 170. 08036, Barcelona, Spain.
Valero
Ricard
R
Almenara
Raul
R
Barros
Pablo
P
Capdevila
Lluis
L
López-Boado
Miguel A
MA
Ruiz
Angel
A
Sánchez-Crivaro
Florencia
F
Miquel
Rosa
R
Deulofeu
Ramon
R
Taurá
Pilar
P
Manyalich
Martí
M
García-Valdecasas
Juan C
JC
D000241:Adenosine / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D005982:Glutathione Transferase / Q000096:biosynthesis; D006085:Graft Survival; D006820:Hyaluronic Acid / Q000096:biosynthesis; D007511:Ischemia; D019194:Ischemic Preconditioning; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008102:Liver Circulation; D016031:Liver Transplantation / Q000379:methods*; D009569:Nitric Oxide / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000502:physiology; D043683:Receptors, Adenosine A2 / Q000502:physiology; D015427:Reperfusion Injury; D013552:Swine; D013997:Time Factors; D014019:Tissue Donors; D019172:Transplantation Conditioning; D019820:Xanthine / Q000378:metabolism
D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D019820:Xanthine; D009569:Nitric Oxide; D006820:Hyaluronic Acid; D000242:Cyclic AMP; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000241:Adenosine