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.
Ytrebø
L M
LM
Dept of Digestive Surgery, University Hospital Northern Norway, Tromsø. larsmy@fagmed.uit.no
Nedredal
G I
GI
Langbakk
B
B
Revhaug
A
A
D000818:Animals; D001774:Blood Chemical Analysis; D001780:Blood Coagulation Tests; D005260:Female; D006439:Hemodynamics; D007427:Intracranial Pressure / Q000502:physiology; D008102:Liver Circulation / Q000502:physiology; D017114:Liver Failure, Acute / Q000097:blood / Q000628:therapy*; D008111:Liver Function Tests; D019164:Liver, Artificial; D023421:Models, Animal; D010101:Oxygen Consumption / Q000502:physiology; D012039:Regional Blood Flow; D013552:Swine; D016482:Urinalysis