Hoxworth J M, Xu K, Zhou Y, Lust W D, LaManna J C
Department of Neurology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106-4938, USA.
Brain Res. 1999 Mar 13;821(2):467-79. doi: 10.1016/s0006-8993(98)01332-8.
Cortical metabolites and regional cerebral intracellular pH (pHi) were measured in normoglycemic (NM), acute hyperglycemic (AH), and chronic hyperglycemic (CH, 2 week duration, streptozotocin-induced) Wistar rat brains during cardiac arrest and resuscitation. During total ischemia in AH and CH rats (plasma glucose approximately 30 mM), cortical ATP, PCr, glucose, and glycogen all fell significantly as expected. Lactate levels increased dramatically in association with a concomitant intracellular acidosis. Although lactate reached higher concentrations in AH and CH than NM, pHi was significantly lower only in the AH group. With 5 min of reperfusion, all groups recovered to near baseline in all variables, though lactate remained elevated. In a separate aspect of the study, animals from each experimental group were allowed to recover for 4 days following resuscitation, with outcome being gauged by mortality rate and hippocampal CA1 neuron counts. NM survival rate was significantly better than AH and CH. In particular, no CH rats survived for 4 days despite rapid initial recovery. After 4 days, the AH group had suffered significantly greater CA1 neuron loss than the NM rats. In summary, our research identified differences in intra-ischemic acid-base status in the two hyperglycemic groups, suggesting that chronic hyperglycemia may alter the brain's buffering capacity. These observations may account for differences between acutely and chronically hyperglycemic subjects regarding outcome, and they suggest that factors other than hydrogen ion production during ischemia are responsible for modulating outcome.
在心脏骤停和复苏期间，对正常血糖（NM）、急性高血糖（AH）和慢性高血糖（CH，持续2周，链脲佐菌素诱导）的Wistar大鼠脑内的皮质代谢物和局部脑内细胞内pH（pHi）进行了测量。在AH和CH大鼠（血浆葡萄糖约30 mM）的完全缺血期间，皮质ATP、磷酸肌酸（PCr）、葡萄糖和糖原均如预期显著下降。乳酸水平显著升高，同时伴有细胞内酸中毒。尽管AH和CH组的乳酸浓度高于NM组，但仅AH组的pHi显著更低。再灌注5分钟后，所有组的所有变量均恢复至接近基线水平，不过乳酸仍保持升高。在该研究另一个方面，每个实验组的动物在复苏后允许恢复4天，通过死亡率和海马CA1神经元计数来评估结果。NM组的存活率显著高于AH组和CH组。特别是，尽管最初恢复迅速，但没有CH大鼠存活4天。4天后，AH组的CA1神经元损失比NM大鼠显著更严重。总之，我们的研究确定了两个高血糖组在缺血期酸碱状态上的差异，表明慢性高血糖可能会改变大脑的缓冲能力。这些观察结果可能解释了急性和慢性高血糖受试者在预后方面的差异，并且表明缺血期间除氢离子产生之外的其他因素负责调节预后。
