GLUTAMINE, MYOINOSITOL, AND ORGANIC BRAIN OSMOLYTES AFTER PORTACAVAL ANASTOMOSIS IN THE RAT - IMPLICATIONS FOR AMMONIA-INDUCED BRAIN EDEMA

Brain myo-inositol, an organic osmolyte, is decreased in cirrhotic pat ients with hepatic encephalopathy but appears unchanged in fulminant h epatic failure. An osmoregulatory response to the increase in brain gl utamine may explain the decrease in brain myo-inositol; if this is the case, organic osmolytes may account for differences in the developmen t of brain edema seen in acute or chronic liver failure. The response of myo-inositol and nine other organic osmolytes to the increase in br ain glutamine at different time intervals after portacaval anastomosis (PCA) in the rat was studied. Organic osmolytes were measured in brai n tissue and cerebrospinal fluid. Water in cerebral cortex was measure d 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 cont ent 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 myoinositol 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 bot h time points. In conclusion, the reduction in brain myo-inositol in P CA rats is accompanied by the decrease of other organic osmolytes, sup porting the view that changes in myo-inositol reflect an osmoregulator y 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 am monia 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 b rain edema in fulminant hepatic failure.