The Effect of Normothermic Recirculation is Mediated by Ischemic Preconditioning in NHBD Liver Transplantation

Abstract

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.

Ischemic Pre-conditioning in Deceased Donor Liver Transplantation: A Prospective Randomized Clinical Trial

“…The high uric acid levels in the IPC group in our study suggest a better cell environment to eliminate toxic substances such as hypoxanthine and xanthine during reperfusion. This data correlates well with the decrease in hyaluronic acid in the IPC group, as a marker of endothelial cell injury after reperfusion (38).…”

Liver transplantation using uncontrolled non-heart-beating donors under normothermic extracorporeal membrane oxygenation

“…Although some authors were not able to demonstrate any difference depending on the bypass temperature, 4 there is evidence based on experimental porcine models that supports the use of normothermic recirculation of oxygenated blood at 37°C. 21,22 According to Net et al, 23 NECMO could shift the warm ischemia time to an ischemic preconditioning period, providing greater viability to UNHBD livers.…”

Kidneys from uncontrolled donors after cardiac death: which kidneys do worse?

“…The use of normothermic extracorporeal membrane oxygenation (ECMO) after cardiac arrest may be a valuable alternative for hypothermic ISP with the DBTL catheter. Advantages of ECMO include recirculation of oxygenated blood until organ procurement, maintaining or restoring adenosine-levels, and it may offer the opportunity of viability testing of normothermic perfused kidneys [34,35]. This technique has the potential to improve organ quality of ischemically damaged uncontrolled DCD kidneys with better graft function and graft survival [36,37].…”