An Experimental Large Animal Model for the Assessment of Bioartificial Liver Support Systems in Fulminant Hepatic Failure

BACKGROUND: Pre-clinical assessment of bioartificial liver support systems requires a highly reproducible large animal model. The main objective of the present study was to develop a valid large animal model for assessing novel bioartificial liver support systems in fulminant hepatic failure. METHODS: A complete liver devascularization procedure was performed in 10 female pigs weighing 25-38 kg. Five matched pigs were sham-operated and served as controls. RESULTS: Pigs with fulminant hepatic failure developed a hyperdynamic circulation, with increased cardiac index (P(GT) < .0001), decreased systemic vascular resistance index (P(GT) < .0001) and mean arterial pressure (P(GT) = .001). Furthermore, intracranial hypertension developed (P(GT) < .0001). with increased common carotid artery flow (P(GT) < .0001) and decreased common carotid resistance (P(G) = .003). Femoral artery flow increased (P = .036). while hindleg resistance (P < .001) and renal artery resistance decreased (P = .019). Oxygen consumption (P(GT) = .050) and oxygen extraction ratio (P(GT) = .001) increased compared to controls. Arterial ammonia, venous aspartate aminotransferase and bilirubin levels increased (P(GT) < .0001, respectively). Abnormal haemostasis developed with significant loss of platelets (P(GT) = .010), decreasing fibrinogen levels (P(G) = .001) and increasing international normalized ratio (P(GT) = .012) and activated clotting time (PGT < .001). Urine became hypo-osmotic (P < .001. P(G) = .011), with decreased sodium levels (P = .08) and increased potassium levels (P(G) = .025). CONCLUSIONS: This study characterizes a reproducible large animal model for fulminant hepatic failure that seems suitable for the assessment of bioartificial liver support systems.