Azotemia (48 h) decreases the risk of brain damage in rats after correction of chronic hyponatremia

Brain Res. 2000 Jan 3;852(1):167-72. doi: 10.1016/s0006-8993(99)02259-3.

Abstract

Brain myelinolysis complicates excessive correction of chronic hyponatremia in man. Myelinolysis appear in rats for correction levels deltaSNa) > 20 mEq/l/24 h. We previously showed in rats that when chronic hyponatremia was corrected with urea, the incidence and the severity of brain lesions were significantly reduced compared to hypertonic saline. In man, hyponatremia is frequently associated with azotemia and hemo-dialysis usually corrects rapidly the serum sodium (SNa) but only few patients apparently develop demyelination. We hypothesize that uremic state protects brain against myelinolysis. This hypothesis was evaluated in rats developing azotemia by administration of mercuric chloride (HgCl2, 1.5 mg/kg). Severe (SNa < 120 mEq/l) hyponatremia (3 days) was induced by S.C. AVP and i.p. 2.5% D-glucose for 3 days. HgCl2 was injected on day 2. Hyponatremia was corrected on day 4 by i.p. injections of 5% NaCl in order to obtain a correction level largely above the toxic threshold for brain (deltaSNA approximately 30 mEq/l/24 h). Surviving rats were decapitated on day 10 for brain analysis. In the group with renal failure (Group I, n = 15, urea 59 mmol/l) the outcome was remarkably favourable with only three rats (3/15) dying before day 10 and only one of them (1/3) presenting myelinolysis-related neurologic symptoms. The 12 other rats (80%) survived in Group I without symptoms and brain analysis was normal in all of them despite large correction level (deltaSNa: 32 mEq/l/24 h). On the contrary in nine rats in which HgCl, did not produce significant azotemia (control 1, n = 9, urea: 11 mmol/l), all the rats developed severe neurologic symptoms and eight of them died before day 10. Similar catastrophic outcome was observed in the non-azotemic controls (control 2, no HgCl2 administration, n = 15, urea: 5 mmol/l). All of them developed myelinolysis-related neurologic symptoms and only four of them survived with severe brain lesions (survival 12/15 in Group I vs. 5/24 in pooled controls 1 and 2, p < 0.001). In conclusion, we showed for the first time that chronic hyponatremic rats with azotemia (48 h) tolerated large increases in SNa (approximately 30 mEq/l/24 h) without significant brain damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Damage, Chronic / prevention & control*
  • Chronic Disease
  • Hyponatremia / blood
  • Hyponatremia / drug therapy*
  • Kidney Failure, Chronic / mortality
  • Male
  • Myelinolysis, Central Pontine / prevention & control
  • Nervous System Diseases / etiology
  • Rats
  • Rats, Wistar
  • Risk Factors
  • Sodium / blood
  • Sodium Chloride / therapeutic use*
  • Uremia / physiopathology*

Substances

  • Sodium Chloride
  • Sodium