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

Abstract

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.

• Acute Liver Failure
• Bioartificial Liver
• Experimental