The Effect of Normothermic Recirculation is Mediated by Ischemic Preconditioning in NHBD Liver Transplantation
Article first published online: 28 JUL 2005
American Journal of Transplantation
Volume 5, Issue 10, pages 2385–2392, October 2005
How to Cite
Net, M., Valero, R., Almenara, R., Barros, P., Capdevila, L., López-Boado, M. A., Ruiz, A., Sánchez-Crivaro, F., Miquel, R., Deulofeu, R., Taurá, P., Manyalich, M. and García-Valdecasas, J. C. (2005), The Effect of Normothermic Recirculation is Mediated by Ischemic Preconditioning in NHBD Liver Transplantation. American Journal of Transplantation, 5: 2385–2392. doi: 10.1111/j.1600-6143.2005.01052.x
- Issue published online: 28 JUL 2005
- Article first published online: 28 JUL 2005
- Received 4 October 2004, revised 30 May 2005 and accepted for publication 22 June 2005
- cardiopulmonary bypass;
- nitric oxide;
- total body cooling
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.