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In previous studies we noted a disruption of the circadian locomotor activity rhythm in rats after portacaval anastomosis (PCA). To examine whether this abnormality is related to factors that aggravate hepatic encephalopathy in humans, we studied the effect of dietary formulation and protein content on body weight, locomotor activity, and entrainment to the light-dark cycle in rats after PCA or sham operation. Postoperative weight loss was prevented by pair-feeding with a purified liquid diet. However, the behavioral abnormalities persisted in PCA rats fed a high-protein diet, with a reduction in total activity and entrainment to the light-dark cycle. These were ameliorated by a low dietary protein content. Since this treatment reduces the load of gut-derived nitrogenous substances that might alter brain metabolism, our data strengthen the hypothesis that the abnormal circadian activity patterns in PCA rats may be part of the spectrum of hepatic encephalopathy.

Variability in experimental results have led to criticism regarding the validity of the rat after portacaval anastomosis (PCA) as a model of changes induced by portal-systemic shunting (PSS). A nonsuture technique using cyanoacrylate glue has been reported to yield a better experimental preparation. To investigate if variations in splanchnic hemodynamics could explain different outcomes after the procedure, male rats received either an end-to-side PCA or sham operations (16 rats each). The PCA was constructed using the "suture" or "glue" technique (8 rats each). Beginning on postoperative day 24 under methoxyflurane and ketamine anesthesia, pressures were recorded from the portal vein, inferior vena cava, and femoral artery. Blood flow to the splanchnic organs and the percent PSS were assessed using the microsphere technique. The rate of delivery of NH3 from the portal vein to the systemic circulation and the concentration of glutamine in the cerebrospinal fluid were determined. In PCA rats, weight gain was significantly impaired, and all animals had evidence of liver atrophy (in both suture and glue groups) when compared with sham animals; a trend toward greater weight gain was seen in glue rats. Portal vein inflow, PSS, NH3 delivery, and CSF glutamine were significantly increased in both PCA-suture and PCA-glue animals compared with sham rats, although no significant differences were seen between the two PCA techniques. When PCA rats from either technique were grouped according to the pressure gradient between portal vein and inferior vena cava, striking differences between animals were now evident.(ABSTRACT TRUNCATED AT 250 WORDS)

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