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Cerebral blood flow and cerebral edema in rats with diabetic ketoacidosis.

Yuen N, Anderson SE, Glaser N, Tancredi DJ, O'Donnell ME - Diabetes (2008)

Bottom Line: CBF was significantly reduced in DKA and was responsive to alterations in pCO(2).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Membrane Biology, University of California, Davis, California, USA.

ABSTRACT

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.

Research design and 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.

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Related in: MedlinePlus

Effect of saline/insulin infusion on ADC values and CBF in DKA rats. Rats were infused with saline and insulin intravenously via cannulated femoral vein, as described in research design and methods. A: ADC values of DKA rat cortex and striatum were determined by diffusion-weighted imaging before, as well as 1 and 2 h after, the start saline/insulin fusion. Values are means ± SE, n = 6. *Significantly different from preinfusion ADC values by paired t test. P < 0.05 for both cortex and striatum at 2 h. One-hour values are not significantly different from pretreatment values. B: CBF values of DKA rat cortex and striatum were determined by perfusion-weighted imaging before, as well as 1 and 2 h after, the start of saline/insulin infusion. Values are means ± SE, n = 6. *Significantly different from preinfusion CBF values by paired t test. P < 0.01 and P < 0.001 for cortex at 1 and 2 h, respectively; P < 0.05 and P < 0.01 for striatum at 1 and 2 h, respectively. □, before saline/insulin; , 1 hr after saline/insulin; ▪, 2 hr after sasline/insulin.
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f4: Effect of saline/insulin infusion on ADC values and CBF in DKA rats. Rats were infused with saline and insulin intravenously via cannulated femoral vein, as described in research design and methods. A: ADC values of DKA rat cortex and striatum were determined by diffusion-weighted imaging before, as well as 1 and 2 h after, the start saline/insulin fusion. Values are means ± SE, n = 6. *Significantly different from preinfusion ADC values by paired t test. P < 0.05 for both cortex and striatum at 2 h. One-hour values are not significantly different from pretreatment values. B: CBF values of DKA rat cortex and striatum were determined by perfusion-weighted imaging before, as well as 1 and 2 h after, the start of saline/insulin infusion. Values are means ± SE, n = 6. *Significantly different from preinfusion CBF values by paired t test. P < 0.01 and P < 0.001 for cortex at 1 and 2 h, respectively; P < 0.05 and P < 0.01 for striatum at 1 and 2 h, respectively. □, before saline/insulin; , 1 hr after saline/insulin; ▪, 2 hr after sasline/insulin.

Mentions: We next evaluated ADC and CBF values in DKA rats before saline/insulin infusion and also 1 and 2 h after the start of infusion. Figure 4 shows that saline/insulin infusion caused a modest increase in ADC values of the cortex and striatum after 2 h (3.3 and 8.0%, respectively) while having no significant effect after 1 h. In contrast, saline/insulin infusion significantly increased CBF in the cortex of DKA rats (27 and 42% after 1 and 2 h, respectively) as well as in the striatum (19 and 28% in the striatum after 1 and 2 h, respectively). Evaluating these data for mean absolute increases and mean percent increases in ADC and CBF values relative to baseline values for each animal revealed the same results as shown in Fig. 4 with respect to presence or absence of significant changes (not shown).


Cerebral blood flow and cerebral edema in rats with diabetic ketoacidosis.

Yuen N, Anderson SE, Glaser N, Tancredi DJ, O'Donnell ME - Diabetes (2008)

Effect of saline/insulin infusion on ADC values and CBF in DKA rats. Rats were infused with saline and insulin intravenously via cannulated femoral vein, as described in research design and methods. A: ADC values of DKA rat cortex and striatum were determined by diffusion-weighted imaging before, as well as 1 and 2 h after, the start saline/insulin fusion. Values are means ± SE, n = 6. *Significantly different from preinfusion ADC values by paired t test. P < 0.05 for both cortex and striatum at 2 h. One-hour values are not significantly different from pretreatment values. B: CBF values of DKA rat cortex and striatum were determined by perfusion-weighted imaging before, as well as 1 and 2 h after, the start of saline/insulin infusion. Values are means ± SE, n = 6. *Significantly different from preinfusion CBF values by paired t test. P < 0.01 and P < 0.001 for cortex at 1 and 2 h, respectively; P < 0.05 and P < 0.01 for striatum at 1 and 2 h, respectively. □, before saline/insulin; , 1 hr after saline/insulin; ▪, 2 hr after sasline/insulin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2551666&req=5

f4: Effect of saline/insulin infusion on ADC values and CBF in DKA rats. Rats were infused with saline and insulin intravenously via cannulated femoral vein, as described in research design and methods. A: ADC values of DKA rat cortex and striatum were determined by diffusion-weighted imaging before, as well as 1 and 2 h after, the start saline/insulin fusion. Values are means ± SE, n = 6. *Significantly different from preinfusion ADC values by paired t test. P < 0.05 for both cortex and striatum at 2 h. One-hour values are not significantly different from pretreatment values. B: CBF values of DKA rat cortex and striatum were determined by perfusion-weighted imaging before, as well as 1 and 2 h after, the start of saline/insulin infusion. Values are means ± SE, n = 6. *Significantly different from preinfusion CBF values by paired t test. P < 0.01 and P < 0.001 for cortex at 1 and 2 h, respectively; P < 0.05 and P < 0.01 for striatum at 1 and 2 h, respectively. □, before saline/insulin; , 1 hr after saline/insulin; ▪, 2 hr after sasline/insulin.
Mentions: We next evaluated ADC and CBF values in DKA rats before saline/insulin infusion and also 1 and 2 h after the start of infusion. Figure 4 shows that saline/insulin infusion caused a modest increase in ADC values of the cortex and striatum after 2 h (3.3 and 8.0%, respectively) while having no significant effect after 1 h. In contrast, saline/insulin infusion significantly increased CBF in the cortex of DKA rats (27 and 42% after 1 and 2 h, respectively) as well as in the striatum (19 and 28% in the striatum after 1 and 2 h, respectively). Evaluating these data for mean absolute increases and mean percent increases in ADC and CBF values relative to baseline values for each animal revealed the same results as shown in Fig. 4 with respect to presence or absence of significant changes (not shown).

Bottom Line: CBF was significantly reduced in DKA and was responsive to alterations in pCO(2).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Membrane Biology, University of California, Davis, California, USA.

ABSTRACT

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.

Research design and 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.

Show MeSH
Related in: MedlinePlus