REINDUCTION OF HYPONATREMIA IMPROVES SURVIVAL IN RATS WITH MYELINOLYSIS-RELATED NEUROLOGIC SYMPTOMS

Brain myelinolysis occurs after excessive correction (Delta SNa > 20 m Eq/1/24 hours) of chronic hyponatremia. However, we showed recently th at the mechanisms leading to brain myelinolysis remain reversible. Ind eed, reinduction of the hyponatremia by water administration despite 1 2 hours of sustained excessive correction could prevent the developmen t of demyelination in rats still asymptomatic at that time. Whether th is therapeutic maneuver could be also beneficial to rats with preexist ing myelinolysis-related neurologic symptoms is unknown. Therefore we evaluated here the effect of reinduction of the hyponatremia on the su rvival and on brain damage in rats presenting obvious neurologic sympt oms after excessive correction of hyponatremia. After 3 days of severe hyponatremia induced by 2.5 D-glucose in water and continuous infusio n of AVP, rats were submitted to a large correction (Delta SNa similar to 30 mEq/l) by 2 i.p. injections of hypertonic saline given over 24 hours. In group I (n = 15) the rats developing neurologic symptoms dur ing the first 24 hours of correction received one i.p. injection of di stilled water which rapidly decreased the natremia to a final correcti on gradient < 20 mEq/1/24 hour. In group II (n = 13, controls) the sym ptomatic rats were left permanently overcorrected. In group I, after w ater administration, the neurological manifestations were generally at tenuated or disappeared. Seven of the 15 rats (47%) in this group surv ived up to day 10 with a mean survival time of 7.5 +/- 2 days, an outc ome clearly improved as compared to group TT (controls): only 1 of the 13 rats (7%, p < 0.03) was still alive on day 10 and the mean surviva l time was 3.3 +/- 2 days (p < 0.001) in this group II. The duration o f the symptoms also influences the prognosis. In group I, in 9 rats th e water administration was performed 4 hours after symptoms onset. The se rats had a better outcome than the 6 rats with more sustained (8-10 hours) neurologic symptoms before water loading. Brain analysis in th e 7 surviving rats of group I demonstrated demyelinating lesions in on ly 2 of them, suggesting the reversibility of the process even when ne urologic manifestation developed. In conclusion, after exposure to an excessive correction of chronic hyponatremia, even when rats have deve loped myelinolysis-related neurologic symptoms, hypotonic fluids admin istration could improve survival and could prevent the subsequent deve lopment of brain myelinolysis.