Chronic hyponatremia exacerbates ammonia-induced brain edema in rats after portacaval anastomosis

J Hepatol. 1998 Oct;29(4):589-94. doi: 10.1016/s0168-8278(98)80154-2.


Background/aim: Abnormalities in brain organic osmolytes are associated with hepatic encephalopathy and with chronic hyponatremia. In spite of the high frequency of hyponatremia in acute and chronic hepatic failure, its role in the development of neurological complications in liver disease is poorly understood. We aimed to study the effect of prior hyponatremia on the development of ammonia-induced brain edema in rats after portacaval anastomosis. In this model, brain swelling is mediated in part through an increase in brain glutamine, an organic osmolyte.

Methods: Hyponatremia was induced in rats with 1-desamino-8-D-arginine vasopressin (DDAVP) administered through an osmotic minipump for 1 week. This was followed by performance of a portacaval anastomosis and ammonia infusion. At the end of the infusion, brain water (density gradient) 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. Hyperammonemia resulted in the expected rise in glutamine, with a reduction of myo-inositol and taurine. In the combined group (hyponatremia plus hyperammonemia), 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 infusion to hyponatremic rats exacerbated brain swelling (82.3+/-0.3% vs. 80.6+/-0.1%; p<0.05).

Conclusions: Hyponatremia worsens brain swelling in a model of ammonia-induced brain edema. The decrease in the concentration of brain organic osmolytes induced by hyponatremia does not protect the brain from the development of ammonia-induced brain edema.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Ammonia / toxicity*
  • Animals
  • Brain / metabolism
  • Brain Edema / etiology*
  • Chronic Disease
  • Hepatic Encephalopathy / metabolism
  • Hyponatremia / complications*
  • Male
  • Portacaval Shunt, Surgical
  • Rats
  • Rats, Sprague-Dawley


  • Ammonia