CHRONIC HYPONATREMIA EXACERBATES AMMONIA-INDUCED BRAIN EDEMA IN RATS AFTER PORTACAVAL ANASTOMOSIS

Background/Aim: Abnormalities in brain organic osmolytes are associate d with hepatic encephalopathy and with chronic hyponatremia. In spite of the high frequency of hyponatremia in acute and chronic hepatic fai lure, its role in the development of neurological complications in liv er disease is poorly understood. We aimed to study the effect of prior hyponatremia on the development of ammonia-induced brain edema in rat s after portacaval anastomosis. In this model, brain swelling is media ted in part through an increase in brain glutamine, an organic osmolyt e. Methods: Hyponatremia was induced in rats with 1-desamino-8-D-argin ine vasopressin (DDAVP) administered through an osmotic minipump for 1 week. This was followed by performance of a portacaval anastomosis an d ammonia infusion. At the end of the infusion, brain water (density g radient) and key brain organic osmolytes (HPLC) were measured. Results : Rats with hyponatremia showed a decrease in all three brain organic osmolytes measured: glutamine, myo-inositol and taurine, Hyperammonemi a resulted in the expected rise in glutamine, with a reduction of myo- inositol and taurine. In the combined group (hyponatremia plus hyperam monemia), the rise in brain glutamine induced by ammonia infusion was attenuated (10.6+/-0.9 mM/kg vs. 15.5+/-0.8 mM/kg hyperammonemia alone ; p<0.05). In spite of this limited rise in brain glutamine, ammonia i nfusion to hyponatremic rats exacerbated brain swelling (82.3+/-0.3 % vs. 80.6+/-0.1%; p<0.05). Conclusions: Hyponatremia worsens brain swel ling in a model of ammonia-induced brain edema. The decrease in the co ncentration of brain organic osmolytes induced by hyponatremia does no t protect the brain from the development of ammonia-induced brain edem a.