Effects of a branched-chain amino acid-enriched diet on chronic hepatic encephalopathy in dogs

A decreased ratio of branched-chain amino acids (BCAA) to aromatic amino ac ids (AAA) is considered an important pathogenetic factor in hepatic encepha lopathy (HE). A relationship between the deranged BCAA/AAA ratio and dopami nergic dysfunction through the formation of "false" neurotransmitters has b een postulated. The intermediate lobe of the pituitary is more pronounced i n dogs than in humans and because it is primarily under dopaminergic inhibi tory influence, it may serve as an indicator of alterations in dopaminergic neurotransmission. We investigated the effects of a diet with a high BCAA/ AAA ratio (HR) and an isonitrogenous diet with a low BCAA/AAA ratio (LR) on several physical and biochemical parameters including pituitary function i n dogs with portocaval shunts and 40% hepatectomy and in sham-operated pair -fed controls, in a double-blind, randomized cross-over study. Portocaval-s hunted dogs had hyperammonemia (33 +/- 3 mu M (mean +/- SEM) before and 214 +/- 21 after surgery)) and signs of HE. Their BCAA/AAA ratio in plasma and CSF decreased from 4.3 +/- 0.3 and 2.3 +/- 0.3 before surgery to 1.3 +/- 0 .1 and 0.5 +/- 0.1 after surgery, respectively. These parameters remained u naltered in the control dogs. The consumption of the LR diet was significan tly higher than consumption of the HR diet. In the portocaval-shunted dogs, plasma ammonia concentration was higher on the HR diet than on the LR diet (344 +/- 52 v 246 +/- 45) and the HE grade was worse. The BCAA /AAA ratio remained abnormal in HE dogs during the feeding of both diets. The basal an d haloperidol-stimulated release of alpha-melanotropin and cortisol in plas ma were not significantly different between or within groups during any per iod. In contrast, urinary cortisol excretion was increased in the HE dogs a fter surgery (urinary cortisol:creatinine ratio (x10(-6)) 8.5 +/- 1.4 befor e and 30.4 +/- 8.9 after surgery). The basal plasma concentration of adreno corticotropin in HE dogs was decreased after surgery (68.3 +/- 10.2 ng/L be fore and 40.8 +/- 4.4 after surgery). This indicates a non-pituitary-depend ent hyperresponsiveness of the adrenals. We conclude from these results tha t chronic HE in dogs is not associated with an abnormal dopaminergic neurot ransmission at least at the level of the pituitary, and that it is not the content of the dietary neutral amino acids but rather the total protein int ake that may have a beneficial effect on HE.