Cerebral blood flow and cerebral edema in rats with diabetic ketoacidosis.
OBJECTIVE
Cerebral edema (CE) is a potentially life-threatening complication of diabetic ketoacidosis (DKA) in children. Osmotic fluctuations during DKA treatment have been considered responsible, but recent data instead suggest that cerebral hypoperfusion may be involved and that activation of cerebral ion transporters may occur. Diminished cerebral blood flow (CBF) during DKA, however, has not been previously demonstrated. We investigated CBF and edema formation in a rat model of DKA and determined the effects of bumetanide, an inhibitor of Na-K-Cl cotransport.


METHODS
Juvenile rats with streptozotocin-induced DKA were treated with intravenous saline and insulin, similar to human treatment protocols. CBF was determined by magnetic resonance (MR) perfusion-weighted imaging before and during treatment, and CE was assessed by determining apparent diffusion coefficients (ADCs) using MR diffusion-weighted imaging.


RESULTS
CBF was significantly reduced in DKA and was responsive to alterations in pCO(2). ADC values were reduced, consistent with cell swelling. The reduction in ADCs correlated with dehydration, as reflected in blood urea nitrogen concentrations. Bumetanide caused a rapid rise in ADCs of DKA rats without significantly changing CBF, while saline/insulin caused a rapid rise in CBF and a gradual rise in ADCs. DKA rats treated with bumetanide plus saline/insulin showed a trend toward more rapid rise in cortical ADCs and a larger rise in striatal CBF than those observed with saline/insulin alone.


CONCLUSIONS
These data demonstrate that CE in DKA is accompanied by cerebral hypoperfusion before treatment and suggest that blocking Na-K-Cl cotransport may reduce cerebral cell swelling.
Yuen
Natalie
N
Department of Physiology and Membrane Biology, University of California, Davis, California, USA.
Anderson
Steven E
SE
Glaser
Nicole
N
Tancredi
Daniel J
DJ
O'Donnell
Martha E
ME
D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002034:Bumetanide / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D016883:Diabetic Ketoacidosis / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology
D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide