STENOSIS OF A PORTACAVAL ANASTOMOSIS AFFECTS CIRCADIAN LOCOMOTOR-ACTIVITY IN THE RAT - A MULTIVARIABLE ANALYSIS

The study of hepatic encephalopathy is limited by the lack of standard ized experimental models to assess behavior. We have shown that rats c ontinuously monitored while running on a wheel show abnormalities of t he circadian rhythm of locomotor activity after portacaval anastomosis (PCA), such that entrainment of running activity to the light-dark cy cle is severely impaired. To identify factors that affect postoperativ e circadian behavior, we have performed a multivariable analysis of 69 sham-operated controls and 107 rats after PCA. Our results indicate t hat shunt stenosis, as determined by the pressure gradient from the sp lenic pulp to the inferior vena cava, ameliorated the postoperative de terioration of the circadian rhythm. In addition, postoperative behavi or was affected by preoperative performance, diet, and gender. Postope rative body weight gain, spleen weight, and liver atrophy did not impa ct this model. Because shunt stenosis is known to ameliorate hepatic e ncephalopathy in humans, our findings support the validity of this beh avioral end point as a correlate of hepatic encephalopathy. Measuremen t of the pressure gradient across the anastomosis and achievement of s ufficient preoperative entrainment appear critical for the standardiza tion of the model.