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 portal-systemic encephalopathy (PSE) in rats with a surgically constructed portacaval anastomosis (PCA).


METHODS
The ability of increasing the load of nitrogenous substances in the gastrointestinal tract and/or further decreasing hepatocellular function to induce overt encephalopathy in rats with a PCA was determined.


METHODS
The load of nitrogenous substances in the gastrointestinal tract was increased by feeding a pure horse-meat diet or by gavaging with blood. Partial hepatectomy and the induction of cirrhosis were used to decrease hepatocellular function further. The severity of encephalopathy was assessed using a neurobehavioural scale.


RESULTS
Overt encephalopathy was not induced in rats by a PCA alone, by a PCA plus a horse-meat diet, by a PCA plus induction of cirrhosis, or by a PCA plus a 50% hepatectomy. Predominantly mild, but overt, encephalopathy was induced in rats with a PCA alone by gavaging with blood and a higher incidence of more severe overt encephalopathy was induced in rats with a PCA combined with either cirrhosis or partial hepatectomy by gavaging with blood. Although these models of PSE were associated in some instances with plasma ammonia concentrations about 25 times higher than normal, no seizures were observed.


CONCLUSIONS
A syndrome that resembles overt PSE in humans can be induced in the rat with a PCA by further reducing hepatocellular function and also gavaging with blood. Although the rat with a PCA has been. extensively used as a model in studies relating to the pathogenesis of PSE, a syndrome resembling overt PSE in humans cannot readily be induced in rats with a PCA.
Mullen
K D
KD
Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland, USA.
Roessle
M
M
Jones
D B
DB
Grun
M
M
Jones
E A
EA
D000641:Ammonia / Q000097:blood; D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D004195:Disease Models, Animal; D005240:Feasibility Studies; D006498:Hepatectomy; D006501:Hepatic Encephalopathy / Q000209:etiology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced; D008297:Male; D009929:Organ Size; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley
D000641:Ammonia