PRECIPITATION OF OVERT ENCEPHALOPATHY IN THE PORTACAVAL SHUNTED RAT -TOWARDS THE DEVELOPMENT OF AN ADEQUATE MODEL OF CHRONIC PORTAL-SYSTEMIC ENCEPHALOPATHY

Objective: To assess the feasibility of developing a model of overt po rtal-systemic encephalopathy (PSE) in rats with a surgically construct ed portacaval anastomosis (PCA). Design: The ability of increasing the load of nitrogenous substances in the gastrointestinal tract and/or f urther decreasing hepatocellular function to induce overt encephalopat hy in rats with a PCA was determined. Methods: The load of nitrogenous substances in the gastrointestinal tract was increased by feeding a p ure horse-meat diet or by gavaging with blood. Partial hepatectomy and the induction of cirrhosis were used to decrease hepatocellular funct ion further. The severity of encephalopathy was assessed using a neuro behavioural scale. Results: Overt encephalopathy was not induced in ra ts by a PCA alone, by a PCA plus a horse-meat diet, by a PCA plus indu ction of cirrhosis, or by a PCA plus a 50% hepatectomy. Predominantly mild, but overt, encephalopathy was induced in rats with a PCA alone b y gavaging with blood and a higher incidence of more severe overt ence phalopathy was induced in rats with a PCA combined with either cirrhos is or partial hepatectomy by gavaging with blood. Although these model s of PSE were associated in some instances with plasma ammonia concent rations about 25 times higher than normal, no seizures were observed. Conclusion: A syndrome that resembles overt PSE in humans can be induc ed in the rat with a PCA by further reducing hepatocellular function a nd also gavaging with blood. Although the rat with a PCA has been. ext ensively used as a model in studies relating to the pathogenesis of PS E, a syndrome resembling overt PSE in humans cannot readily be induced in rats with a PCA.