Metabolic Effects of a Succinic Acid<Based Substrate Antihypoxant

Abstract

The paper discusses promises for clinical use of substrate antihypoxants.Objective: to investigate the efficacy of succinate containing substrate antihypoxants on systemic oxygen consumption, blood buffer capacity, and changes in the mixed venous blood level of lactate when they are used in gravely sick patients and victims with marked metabolic posthypoxic disorders.Subjects and methods. The trial enrolled 30 patients and victims who had sustained an episode of severe hypoxia of mixed genesis, the severity of which was evaluated by the APACHE II scale and amounted to 23 to 30 scores with a 46 to 70.3% risk of death. The standard infusion program in this group involved the succinate-containing drug 1.5% reamberin solution in a total dose of 800 ml. A comparison group included 15 patients who had undergone emergency extensive surgery for abdominal diseases. 400 ml of 10% glucose solution was used as an infusion medium. Oxygen consumption (VO2ml/min) and carbon dioxide production (VCO2ml/min) were measured before infusion and monitored for 2 hours. Arterial blood gases and acid-base balance (ABB) parameters and mixed venous blood lactate levels were examined. Measurements were made before and 30 minutes after the infusion of reamberin or glucose solution.Results. Infusion of 1.5% reamberin solution was followed by a significant increase in minute oxygen consumption from 281.5±21.2 to 310.4±24.4 ml/min. CO2 production declined (on average, from 223.3±6.5 to 206.5±7.59 ml/min). During infusion of 10% glucose solution, all the patients of the comparison group showed a rise in oxygen consumption from 303.6±33.86 to 443.13±32.1 ml/min, i.e. about 1.5-fold. VCO2 changed similarly. The intravenous infusion of 800 ml of 1.5% reamberin solution raised arterial blood buffer capacity, which was reflected by changes in pH, BE, and HCO3. There was a clear trend for lactate values to drop in the mixed venous blood. The intravenous injection of 400 ml of 10% glucose solution caused no significant changes in major ABB indicators, which reinforced the statement that there is a difference in the metabolism of these substrates.Conclusion. The succinate-containing drugs are able to compensate for metabolic acidosis. Their use is followed by increased oxygen consumption and activated aerobic oxidation processes. The basis of their antihypoxant properties was thought to be recovered intracellular aerobic metabolic processes due to corrected intracellular metabolic acidosis and increased blood buffer capacity.

Keywords

• hypoxia, reperfusion, multiple organ dysfunction, antihypoxants, metabolic acidosis, acid-base balance, lactate, oxygen consumption, succinate, fumarate