A modified surgical model of fulminant hepatic failure in the rat

Abstract

BackgroundThere is a need for better animal models of fulminant liver failure (FHF). Eguchi et al described an interesting surgical model of FHF in the rat. This model includes 68% partial hepatectomy, ischemia of 24% of the liver mass, and 8% of remnant liver left intact. In the original description by Eguchi et al, rats were administered subcutaneous glucose. However, the authors found that normothermic FHF rats with subcutaneous glucose died from deep hypoglycemia. In this report, we describe a modification of that model, and show that administration of intravenous glucose allows better survival and development of intracranial hypertension. MethodsWe operated on FHF rats using the procedure described by Eguchi et al, kept them normothermic, and maintained normoglycemia by continuous intravenous glucose injection (glucose 10%, 1 mL/h). At 24 h, we monitored liver blood tests (n = 5), intracranial pressure (n = 5), clinical encephalopathy, and survival (n = 10), and compared them with sham and 68% hepatectomy rats. ResultsThe FHF rats developed acute cytolysis, cholestasis, and liver failure, as demonstrated by the liver blood tests. They experienced progressive encephalopathy and intracranial hypertension leading to death. Mean survival was 45.9 h. Of 10 FHF rats from the survival evaluation cohort, one survived 7 d. Laparotomy showed necrosis of lateral liver lobes and enlargement of omental lobes with a normal hepatic aspect, suggesting liver recovery. ConclusionsThis surgical rat model mimics the features of human FHF and seems interesting for further research into the pathophysiology and therapeutic management of the disease.