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 (P-GT < .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.