Abstract
Significant protection was demonstrated against the development of convulsive activity in small animals using 0.4 M sodium succinate (1-4) injected intraperitoneally in a dosage of 12 mM/kg of body weight, Succinate protection against hyperbaric oxygen (HPO) at 5, 7, 9, and 11 ATA of 100% oxygen (5) was shown not to be due to the hyperosmolarity of the solution infused and led to our proposal that maintenance of normal ATP concentrations in brain and other tissues is of prime importance in protecting animals subjected to HPO. No significant delay of onset of convulsive activity was observed with hyperosmolar solutions of NaCl, sodium malate, an NAD-linked TCA cycle intermediate, or glucose. These results are consonant with the observation of Chance et al. (6) that HPO adversely affects NAD-linked substrates of oxidative phosphorylation, and have stimulated further studies using the FAD-linked substrates, succinate and alpha-glycerophosphate. We report here the results of experiments using sodium succinate as a protective agent against the toxic effects of HPO in large animals. These studies were carried out to determine the feasibility of using succinate in humans as a protective agent when HPO is used in the treatment of certain clinical conditions such as gas gangrene.
Dogs (12-18 kg) were infused intravenously with 0.4 M sodium succinate, pH 6.4, in a dosage of 8 mM/kg of body weight/hr, for 50 min prior to and during exposure to 100% oxygen at a pressure of 40 psig. Control experiments were conducted by subjecting the same animals, either untreated or infused with equivalent doses of saline or sodium malate, to identical conditions of HPO 48-72 hr prior to the succinate experiments.
Thus, each dog served as its own control, and time to convulsions could be compared directly (Table I).
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