Search

BACKGROUND The aim of the present study was to evaluate hepatic content of adenine nucleotides and their degradation products in non-heart-beating donor (NHBD) pigs and its relationship with recipient survival. METHODS Thirty animals were transplanted with an allograft from NHBDs. After warm ischemia (WI) time (20, 30, or 40 min), cardiopulmonary bypass and normothermic recirculation (NR) were run for 30 min. Afterward, the animals were cooled to 15 degrees C and liver procurement was performed. RESULTS Survival rate was 100% in the 20WI, 70% in the 30WI, and 50% in the 40WI. Livers from non-surviving animals had higher levels of xanthine after NR than livers from surviving animals. Logistic regression analysis revealed that xanthine at the end of NR was the only variable able to predict survival with a calculated sensitivity of 80% and a specificity of 60%. Prolongation of warm ischemic period leaded to a greater xanthine accumulation as well as increased plasma alpha-glutathione S-transferase levels at reperfusion. Xanthine at NR and alpha-glutathione S-transferase at reperfusion significantly correlated, indicating that donor xanthine contributes to some extent to the severity of the lesion by ischemia-reperfusion. CONCLUSIONS It is suggested that xanthine content in the donor is able to predict survival after transplantation. Xanthine is significantly involved in the hepatic lesion elicited by warm ischemia and subsequent ischemia-reperfusion associated to liver transplantation from a NHBD.

Background. Although nitric oxide (NO) is thought to be beneficial in hepatic ischemia-reperfusion (I/R), the mechanisms for this effect are not well established. Methods. To investigate the effects of endogenous NO and exogenous NO supplementation on hepatic I/R injury and their pathogenic mechanisms, serum ALT and hyaluronic acid (endothelial cell damage), and hepatic malondialdehyde and H 2O2 (oxidative stress), myeloperoxidase activity (leukocyte accumulation), and endothelin (vasoconstrictor peptide opposite to NO) were determined at different reperfusion periods in untreated rats and rats receiving L-NAME, L-NAME1L-arginine, and spermine NONOate (exogenous NO donor). Results. After reperfusion every parameter increased in untreated animals. Endogenous NO synthesis inhibition by L-NAME increased hepatocyte and endothelial damage as compared to untreated rats, which was reverted and even improved by the addition of L-arginine. Spermine NONOate also improved this damage. However, different mechanisms account for the beneficial effect of endogenous and exogenous NO. Oxidative stress decreased by both L-NAME and L-NAME1L-arginine, but remained unmodified by spermine NONOate. Myeloperoxidase increased by LNAME and this effect was reverted by the addition of L-arginine, whereas no change was observed with spermine NONOate. Endothelin levels were not modified by L-NAME and L-NAME1L-arginine, but decreased with spermine NONOate. Conclusions. These results suggest that, although both endogenous and exogenous NO exert a protective role in experimental hepatic I/R injury, the mechanisms of the beneficial effect of the two sources of NO are different.

BACKGROUND Our aim was to evaluate the hepatic blood flows and oxygen metabolism of non-heart-beating donor (NHBD) pigs, with the use of cardiopulmonary bypass (CPB) and normothermic recirculation (NR) before total body cooling, and its relationship with recipient survival. METHODS Thirty-five pigs were transplanted with an allograft from NHBDs. After warm ischemia (WI) time (20, 30, or 40 min), CPB and NR were run for 30 min. After this period, the animals were cooled to 15 degrees C. In the control group (20 min of WI), the period of NR was excluded. Liver procurement was then performed. RESULTS Survival rate was 100% in the 20WI, 70% in the 30WI, and 50% in the 40WI. Control group survival rate was 0%. Hepatic artery blood flow and portal blood flow recovered during NR. Pump blood flow during CPB increased rapidly during NR and was significantly higher in the 20WI. When donors of the livers transplanted in "surviving pigs" (DSP) were compared with donors of the livers transplanted in "nonsurviving pigs" (DNSP), hepatic artery blood flow, portal blood flow, and pump blood flow were higher in the DSP. Hepatic oxygen extraction ratio increased in the three groups with respect to baseline values. Hepatic oxygen extraction ratio was lower in the 20WI than in the other groups and was lower in the DSP than in the DNSP. CONCLUSIONS The use of a NR period before total body cooling improves survival of liver transplantation in NHBDs. Portal blood flow and pump blood flow measurements can predict the viability of the grafts.

The aim of this prospective study is to evaluate prostanoid (prostacyclin and thromboxane) and lipid peroxide levels at the portal and hepatic veins, and their relation to immediate postoperative liver function. Nineteen patients with liver cirrhosis undergoing orthotopic liver transplantation were prospectively studied. Blood samples were obtained within 5 min and 1 and 2 hr after reperfusion of the new liver, through a catheter placed at the portal vein in the recipient and another at the left hepatic vein in the donor liver. Plasma prostacyclin and thromboxane were analyzed by HPLC and RIA. The formation of lipid peroxides was determined and expressed in terms of thiobarbituric acid-reacting substances. Immediate postoperative liver function was evaluated using the transaminase levels within the first 48 hr and the early postoperative graft function score, as described previously. After reperfusion, only determinations at 5 min were related with liver function. Either prostacyclin (R = -0.61, P = 0.004) levels at the hepatic vein or prostacyclin production (subtraction between hepatic and portal vein levels) (R = -0.47, P = 0.04) correlated significantly with the early postoperative graft function score. Besides, there was a significant relationship between lipid peroxide production as measured by thiobarbituric acid-reacting substances and a worse early postoperative graft function score (R = 0.61, P = .005). These results suggest that prostacyclin released after liver grafting attenuates preservation and reperfusion damage of the liver, supporting the hypothesis that there is an imbalance of prostanoids within the microvasculature in patients with a compromised postoperative liver function. Our results agree with the involvement of some degree of lipid peroxidation products in the damage of hepatocytes during anoxia and reperfusion.