THE EFFECT OF ALANINE ON LIVER GAFT FUNCTION RECOVERY FOLLOWING COLD ISCHEMIA DEPENDS ON THE NUTRITIONAL STATUS OF THE DONNOR

Arnault Isabelle*, Bao Yang-Ming*, Dimicoli Jean Luc, Lemoine Antoinette*, Bismuth Henri* and Adam René*.

Centre Hépato-biliaire, Hopital Paul Brousse, 14 avenue Paul Vaillant Couturier, 94800 Villejuif.

Unité INSERM, Institut Curie, Batiment 112, Centre Universitaire 91405, Orsay Cedex France

ABSTRACT 

The effect of the donor nutritional status on the recovery of the liver after cold ischemia is still debated. We have shown in a previous study that a 48hour-fasting leads to a lower survival rate of liver transplanted rats and that deleterious effect of fasting may be prevented by the infusion of alanine to the recipient at reperfusion.

We report here an investigation on the effect of fasting periods of different lengths and on the role of alanine infusion on the recovery of the perfused rat liver after cold ischemia. The different fasting period lengths of the donor rat were 24, 48 and 72 hours. The preservation time was 24 hours in UW (4'C), the reperfusion time was 3 hours. The evaluated parameters were : Lactate Deshydrogenase (LDH), Aspartataminotransferase (AST) Alanineaminotransferase (ALT), bile production and vascular resistance. A long fasting period is deleterious as compared to feeding : the release of enzymes (AST, ALT, LDH) in the perfusate is significantly higher after a 72h fasting period. A significant increase in the vascular resistance is also noticed for the 72h fasting livers as compared to those that have been fed. An addition of alanine (8mM) at reperfusion decreases the release of AST, ALT, LDH, after 48h and 72 hours of fasting. In contrast the addition at reperfusion of pyruvate (8mM), a metabolic intermediary of alanine, does not improve the function of livers submitted to a 72hfasting period before preservation. The infusion of alanine compensâtes for the deleterious effect of fasting before cold ischemia. The mechanisms of this protective effect are not metabolic. On a clinical setting, the infusion of alanine to the recipient at reperfusion may be a convenient way to compensate the hyponutrition of the donor.

 

Key words : liver transplantation, alanine, aminoacids, fasting, starvation, cold ischemia.