XANTHINE, A DEGRADATION PRODUCT OF ADENINE NUCLEOTIDES, AS PREDICTOR OF GRAFT VIABILITY IN EXPERIMENTAL PIG LIVER TRANSPLANTATION FROM NON-HEART-BEATING DONORS (NHBD).

Abstract

417 AIM: The search for a useful marker of liver viability after liver procurement from NHBD using normothermic recirculation and total body cooling with cardiopulmonary bypass (CPB). M.M.: 30 out-bread weanling pigs (±30 Kg) were transplanted (LTx) from a NHBD with the following characteristics: Cardiac arrest (CA) was produced by injection of KCl. Each warm ischemia group consisted of 10 pigs with CA periods of 20′ (G20), 30′ (G30), or 40′ (G40) minutes. Normothermic recirculation and tissue oxygenation at 37°C was started using CPB during 30 minutes. Afterwards, the pig was gradually cooled and maintined at 15°C. Ltx was performed after six hours of cold ischemia following the standard procedure. Serum and liver tissue samples were taken (in the donor) at the beginning (BL); at the end of CA (CA) and normothermic recirculation at 37°C (NR); (in the recipient): one hour after reperfusion(RP); and at sacrifice of the animal 5 days post Ltx. Liver tissue adenine nucleotides (ATP, ADP, AMP) and Xanthine and Hypoxanthine were measured by HPLC and their levels were expressed as percentage of total nucleotides in each phase. Cytolysis was assessed by ASAT and GST serum levels and hyaluronic acid (HA) was measured as a marker of liver endothelial damage. RESULTS: Survival of the different groups was 10/10 G20, 7/10 for G30, and 5/10 for G40. As expected increasing CA time increased biochemical markers of liver injury. Dead animals accumulated more xanthine at NR than alive animals (4.73±4.2 vs. 1.64±3.1) reaching statistical significance (p<0.05). Logistic regression analysis showed that xanthine was the only predictive paramenter for survival at the normothermic recirculation phase (p = 0.0049,r = 0.4291). Correlation between xanthine at NR and GST at RP (r=0.58,p=0.022), and between xanthine at NR and histological findings on the fifth day post LTx (r=0.92, p<0.05), were found. CONCLUSION: Xanthine levels at the time of normothermic recirculation could be a good predictive parameter of viability for liver grafts transplanted from NHBD. Other markers as transaminases, GST or hialuronic acid were not good predictors of graft viability. Nevertheless further studies with more animals are needed to confirm these results.