Glutamine, myo-inositol, and organic brain osmolytes after portocaval anastomosis in the rat: implications for ammonia-induced brain edema.

Brain myo-inositol, an organic osmolyte, is decreased in cirrhotic patients with hepatic encephalopathy but appears unchanged in fulminant hepatic failure. An osmoregulatory response to the increase in brain glutamine may explain the decrease in brain myo-inositol; if this is the case, organic osmolytes may account for differences in the development of brain edema seen in acute or chronic liver failure. The response of myo-inositol and nine other organic osmolytes to the increase in brain glutamine at different time intervals after portacaval anastomosis (PCA) in the rat was studied. Organic osmolytes were measured in brain tissue and cerebrospinal fluid. Water in cerebral cortex was measured after ammonia infusion with the gravimetric method. Six weeks after PCA, despite an increase in brain glutamine (PCA, 16.4 +/- 2 mmol.kg wt-1.kg wt-1; sham, 5 +/- 1 mmol.L-1.kg wt-1), the content of total organic osmolytes did not increase (PCA, 44.1 +/- 3; sham, 43 +/- 4) because of a decrease of other osmolytes (myo-inositol, 54%; urea, 39%; taurine, 33%; and glutamate, 8%). Brain myo-inositol was lower at 3 weeks (3.4 +/- 0.5 kg wt-1) than at 1 day after PCA (4.7 +/- 0.5 kg wt-1). An ammonia infusion resulted in brain edema at both time points. In conclusion, the reduction in brain myo-inositol in PCA rats is accompanied by the decrease of other organic osmolytes, supporting the view that changes in myo-inositol reflect an osmoregulatory response. The decrease in brain myo-inositol is more marked as time elapses after PCA. In a model in which short-term and large doses of ammonia were infused, the decrease in brain myo-inositol did not prevent the development of brain swelling. Understanding brain osmoregulatory mechanisms may provide new insights into hepatic encephalopathy and brain edema in fulminant hepatic failure.