Evaluation of ammonia and lidocaine clearance, and galactose elimination capacity of xenoperfused pig livers using a pharmacokinetic analysis

Background. We introduced the pharmacokinetic method into the functional ev aluation of xenogeneic extracorporeal liver perfusion as an artificial live r assist device, and examined the influence of xenogeneic humoral injury on the metabolic function of xenoperfused pig livers. Methods. Isolated pig livers were perfused with fresh porcine blood (group 1; n=5) or fresh human blood (group 2; n=5) for 9 hr. Clearance (CL) of amm onia and lidocaine, and galactose elimination capacity (V-max) were determi ned at three points during the perfusion using a one-compartment pharmacoki netic model. Results. Concentrations of ammonia and lidocaine decreased exponentially an d those of galactose decreased linearly after a bolus injection in both gro ups, A one-compartment model provided satisfactory curve fittings for these test substances. No decreases of ammonia CL, lidocaine CL, or galactose V- max were observed until 9 hr in either group. No differences were observed between the two groups with respect to these metabolic functions. In group 1, only slight interlobular edema was observed at 9 hr, In group 2, membran e attack complex was diffusely deposited at 3 hr and severe interlobular da mage was histologically observed at 9 hr, although hepatocellular damage wa s minimal even at 9 hr, Alpha glutathione S-transferase and mitochondrial a spartate aminotransferase were comparable between the two groups. Conclusions, Pharmacokinetic analysis allowed the evaluation of ammonia CL, lidocaine CL, and galactose V-max of the perfused pig livers, Despite xeno geneic humoral injuries, the xenoperfused livers maintained these metabolic functions at the same levels as the alloperfused livers for 9 hr.