EXTRACORPOREAL APPLICATION OF A GEL-ENTRAPMENT, BIOARTIFICIAL LIVER -DEMONSTRATION OF DRUG-METABOLISM AND OTHER BIOCHEMICAL FUNCTIONS

Metabolic activity of a gel-entrapment, hollow fiber, bioartificial li ver was evaluated in vitro and during extracorporeal hemoperfusion in an anhepatic rabbit model. The bioartificial liver contained either 10 0 million rat hepatocytes (n = 12), fibroblasts (n = 3), or no cells ( n = 7) during hemoperfusion of anhepatic rabbits. Eight other anhepati c rabbits were studied without hemoperfusion as anhepatic controls, an d three sham rabbits served as normal controls. Albumin production rat es (mean +/- SEM) were similar during in vitro (17.0 +/- 2.8 mug/h) an d extracorporeal (18.0 +/- 4.0 mug/h) application of the hepatocyte bi oartificial liver. Exogenous glucose requirements were reduced (p < 0. 01) and euglycemia was prolonged (p < 0.001) in anhepatic rabbits trea ted with the hepatocyte bioartificial liver. The maximum rate of gluco se production by the hepatocyte bioartificial liver ranged from 50-80 mug/h. Plasma concentrations of aromatic amino acids, proline, alanine , and ammonia were normalized in anhepatic rabbits during hepatocyte h emoperfusion. Gel-entrapped hepatocytes in the bioartificial liver per formed sulfation and glucuronidation of 4-methylumbelliferone. P450 ac tivity was demonstrated during both in vitro and extracorporeal applic ation of the BAL device by the formation of 3-hydroxy-lidocaine, the m ajor metabolite of lidocaine biotransformation by gel-entrapped rat he patocytes. In summary, a gel-entrapment, bioartificial liver performed multiple hepatocyte-specific functions without adverse side effects d uring extracorporeal application in an anhepatic, small animal model. With its potential for short term support of acute liver failure, scal e-up of the current bioartificial liver device is indicated for furthe r investigations in large animal, preclinical trials.