Dimlich R V, Timerding B L, Kaplan J, Cammenga R, Van Ligten P F
Department of Emergency Medicine, University of Cincinnati College of Medicine, Ohio 45267-0769.
Ann Emerg Med. 1989 Nov;18(11):1172-80. doi: 10.1016/s0196-0644(89)80054-x.
Excessive brain lactate, as may develop in cerebral ischemia, has been implicated as a major cause of irreversible cell damage. With an experimental model that produces cerebral ischemia by bilateral carotid ligation combined with systemic hypotension, previous studies have shown that treatment with 25 mg/kg sodium dichloroacetate (DCA) is effective in reducing brain lactate more quickly than no treatment at all. Because higher doses of DCA may be more effective, the main objective of our study was to examine the dose-response of brain tissue lactate to DCA. In addition, other metabolites that may be indirectly affected by this response (eg, glucose, glycogen, ATP, and phosphocreatine) also were measured. Adult male Wistar rats were assigned to experimental and treatment groups, and real or sham ischemia was induced as described in our previous article. After 30 minutes of reperfusion, rats were euthanized by in situ freezing of the brain. Cerebral cortex, hippocampus, and cerebellum were analyzed bilaterally. There was no effect of DCA dose on glucose or glycogen. When compared with hippocampus, lactate was higher in the cerebral cortex after ischemia, and DCA was more effective in reducing those levels. This is evidence of a lower metabolic rate in hippocampus than in cortex. Cerebellum did not exhibit an increase in lactate; therefore, it can serve as an in situ tissue control for that metabolite. Significantly different levels of metabolites in one hemisphere of some DCA-treated ischemic rats appeared to reflect a dose effect of DCA on lactate and a significant change in ATP and phosphocreatine at the higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)
脑乳酸过量，如在脑缺血时可能出现的情况，被认为是不可逆细胞损伤的主要原因。通过双侧颈动脉结扎联合全身低血压产生脑缺血的实验模型，先前的研究表明，25mg/kg二氯乙酸钠（DCA）治疗比不治疗能更快速有效地降低脑乳酸。由于更高剂量的DCA可能更有效，我们研究的主要目的是检测脑组织乳酸对DCA的剂量反应。此外，还测量了可能受这种反应间接影响的其他代谢物（如葡萄糖、糖原、三磷酸腺苷和磷酸肌酸）。成年雄性Wistar大鼠被分为实验组和治疗组，按照我们之前文章所述诱导真实或假缺血。再灌注30分钟后，通过原位冷冻大脑使大鼠安乐死。对双侧大脑皮层、海马体和小脑进行分析。DCA剂量对葡萄糖或糖原没有影响。与海马体相比，缺血后大脑皮层中的乳酸含量更高，而DCA在降低这些水平方面更有效。这证明海马体的代谢率低于皮层。小脑的乳酸没有增加；因此，它可作为该代谢物的原位组织对照。一些接受DCA治疗的缺血大鼠的一个半球中代谢物水平存在显著差异，这似乎反映了DCA对乳酸的剂量效应以及高剂量时三磷酸腺苷和磷酸肌酸的显著变化。（摘要截短至250字）
