BRAIN OSMOREGULATION DURING EXTREME AND MODERATE DEHYDRATION IN A RATMODEL OF SEVERE DKA

To determine if osmoprotective molecules accumulate in the brain durin g severe DKA with extreme (DKA-E) and moderate (DKA-M) dehydration, Fi scher 344 rats (250-350g) were given STZ 45 mg/kg (i.p.) and allowed f ood and water ad lib. DKA-M received NaCl 77mmol/L 60 ml/kg (i.p.) q 4 hrs. on day 2. All rats were anesthetized and sacrificed at 48 hrs. H alf of each brain was used to measure water content (BWC) and half to measure Na+, K+, and organic osmoles by HPLC. Just prior to expiration , values for mean concentration of serum glucose (mmol/L) percent weig ht loss and median blood pH for DKA-E were 33.4, 19%, 6.98; for DKA-M, 16.8, 7.5% and 6.84, respectively. Means +/- SEM were compared by Stu dent's t-test. Percent BWC was 76.3, 77.3 and 77.6 in DKA-E, DKA-M and normal controls, respectively (NS) . Brain Na+ and K+ were increased in DKA-M compared to controls (p<.05) but not significantly different in DKA-E compared to controls. Of organic osmoles measured (umol/g wet weight) taurine was significantly increased (p<.01) in DKA-E and DKA- M (8.04 +/- .39 and 9.73 +/-.78, respectively) as compared to controls (5.92 +/- .35) as was myoinositol in DKA-E compared to controls (9.96 +/- .39 vs. 8.87 +/- .28) (p<.05) and urea in DKA-E as compared to co ntrols (14.24 +/- 3.9 vs. 4.14 +/- .52) (p<.01). DKA-M were not signif icantly different for brain myoinositol or urea as compared to control animals. There was no significant difference in brain glutamine betwe en either study group and controls. Preservation of brain water despit e systemic dehydration can be partly explained by increased brain conc entrations of osmoprotective molecules. Such adaption in the clinical setting of DKA warrants a cautious repair of dehydration and hyperosmo lality.