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

Brain myelinolysis complicates excessive correction of chronic hyponatremia in man. Myelinolysis appear in rats for correction levels Delta SNa) > 20 mEq/1/24 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 i s frequently associated with azotemia and hemo-dialysis usually corrects ra pidly the serum sodium (SNa) but only few patients apparently develop demye lination. We hypothesize that uremic state protects brain against myelinoly sis. This hypothesis was evaluated in rats developing azotemia by administr ation of mercuric chloride (HgCl2, 1.5 mg/kg). Severe (SNa < 120 mEq/) hypo natremia (3 days) was induced by S.C, AVP and i.p. 2.5% D-glucose for 3 day s. 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 (Delta SNA similar to 30 mEq/1/24 h). Survivi ng rats were decapitated on day 10 for brain analysis. In the group with re nal failure (Group I, n = 15, urea 59 mmol/l) the outcome was remarkably fa vourable with only three rats (3/15) dying before day 10 and only one of th em (1/3) presenting myelinolysis-related neurologic symptoms. The 12 other rats (80%) survived in Group I without symptoms and brain analysis was norm al in all of them despite large correction level (Delta SNa: 32 mEq/1/24 h) . On the contrary in nine rats in which HgCl2 did not produce significant a zotemia (control 1, n = 9, urea: II mmol/l), all the rats developed severe neurologic symptoms and eight of them died before day 10. Similar catastrop hic 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 bra in 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 hypona tremic rats with azotemia (48 h) tolerated large increases in SNa (similar to 30 mEq/1/24 h) without significant brain damage. (C) 2000 Elsevier Scien ce B.V. All rights reserved.