Cerebral metabolic alterations in rats with diabetic ketoacidosis: effects of treatment with insulin and intravenous fluids and effects of bumetanide.
Cerebral metabolic alterations in rats with diabetic ketoacidosis: effects of treatment with insulin and intravenous fluids and effects of bumetanide.
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DOI：
10.2337/db09-0635
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发表时间：
2010-03
期刊：
影响因子：
7.7
通讯作者：
O'Donnell ME
中科院分区：
文献类型：
--
作者：
Glaser N;Yuen N;Anderson SE;Tancredi DJ;O'Donnell ME
脑水肿是儿童糖尿病酮症酸中毒（DKA）的一种危及生命的并发症。最近的数据表明，脑灌注不足和激活脑离子转运蛋白可能参与，但数据描述脑代谢改变DKA缺乏。我们用质子和磷磁共振波谱（MRS）对50只幼年DKA大鼠和21只正常对照大鼠进行了评估。MRS测定DKA治疗前和治疗中脑细胞内pH值和代谢产物ATP/无机磷酸盐（Pi）、磷酸肌酸（PCr）/Pi、N-乙酰天冬氨酸（NAA）/肌酸（Cr）和乳酸/Cr的比值。我们使用2 × 2析因设计的ANCOVA确定了胰岛素和静脉注射生理盐水加或不加布美他尼（一种Na-K-2Cl共转运抑制剂）治疗的效果。与对照组相比，DKA期间脑细胞内pH值降低（平均值± SE差异-0.13 ± 0.03; P < 0.001），乳酸/肌酐升高（0.09 ± 0.02; P < 0.001）。与对照组相比，DKA大鼠的ATP/Pi和NAA/Cr较低（分别为-0.32 ± 0.10，P = 0.003和-0.14 ± 0.04，P < 0.001），但PCr/Pi没有显著降低。在2小时的治疗与胰岛素/生理盐水，ATP/Pi，PCr/Pi和NAA/Cr显着下降，尽管在细胞内pH值的增加。布美他尼治疗增加ATP/Pi和PCr/Pi和改善这些值的下降与胰岛素/生理盐水治疗。这些数据表明，脑代谢在DKA期间显著受损，并且在早期DKA治疗期间进一步恶化-与脑灌注不足和再灌注损伤的可能影响一致。布美他尼治疗可能有助于减少胰岛素/生理盐水初始治疗的不良反应。
Cerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking. We evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 × 2 factorial study design. Cerebral intracellular pH was decreased during DKA compared with control (mean ± SE difference −0.13 ± 0.03; P < 0.001), and lactate/Cr was elevated (0.09 ± 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (−0.32 ± 0.10, P = 0.003, and −0.14 ± 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment. These data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment—consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline.
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影响因子：
3.4
作者：
Glaser, NS;Wootton-Gorges, SL;Kuppermann, N
通讯作者：
Kuppermann, N
DOI：
10.1073/pnas.93.18.9493
发表时间：
1996-09-03
影响因子：
11.1
作者：
Hochachka, PW;Buck, LT;Land, SC
通讯作者：
Land, SC
影响因子：
6.3
作者：
Ennis, Stenten R.;Keep, Richard F.
通讯作者：
Keep, Richard F.
影响因子：
5.1
作者：
HARRIS, GD;FIORDALISI, I;FINBERG, L
通讯作者：
FINBERG, L
影响因子：
158.5
作者：
KELLER, RJ;WOLFSDORF, JI
通讯作者：
WOLFSDORF, JI