PhD

• RVW Dimlich
  • Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  • Department of Anatomy and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
  • Address for reprints: Ruth VW Dimlich, PhD, Department of Emergency Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45267-0769.

Affiliations

, MD

• BL Timerding
  • Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Affiliations

, MD

• J Kaplan
  • Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Affiliations

, MD

• R Cammenga
  • Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Affiliations

, MD

• PF Van Ligten
  • Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Affiliations

Received 10 January 1989; received in revised form 16 March 1989; accepted 28 July 1989.

A significant contributor to irreversible cell damage has been identified as excessive brain lactate, which can arise in cerebral ischemia. Previous studies have demonstrated that treatment with 25 mg/kg sodium dichloroacetate (DCA) is effective in reducing brain lactate more quickly than no treatment at all when done with an experimental model that causes cerebral ischemia by bilateral carotid ligation combined with systemic hypotension. Our study’s major goal was to look at the brain tissue lactate dose response to DCA because greater doses of the drug may be more efficient. Other metabolites (such as glucose, glycogen, ATP, and phosphocreatine) that may be indirectly impacted by this reaction were also examined. The experimental and treatment groups of adult male Wistar rats were divided, and actual or fictitious ischemia was generated as explained in our prior article. Rats were put to sleep by in situ brain freezing after 30 minutes of reperfusion. Bilateral analyses of the cerebral cortex, hippocampus, and cerebellum were conducted. The dose of DCA had no impact on glucose or glycogen. After ischemia, lactate levels were higher in the cerebral cortex than in the hippocampus, and DCA was more efficient in bringing them down. This shows that the hippocampus has a lower metabolic rate than the cortex. The cerebellum can operate as an in situ tissue control for that metabolite because it did not show a rise in lactate. Some DCA-treated ischemic rats showed significantly different levels of metabolites in one hemisphere, which appeared to reflect a dose effect of DCA on lactate and a significantly different level of ATP and phosphocreatine at the higher doses. Although 25 mg/kg DCA reduces high levels of brain lactate to nonlethal levels, the potential for a greater effect on lactate, ATP, and phosphocreatine at higher doses was revealed by our study.

Link: https://www.annemergmed.com/article/S0196-0644(89)80054-X/abstract