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Hyperbaric Oxygen Toxicity Prevention With Succinate FREE

Aaron P. Sanders, PhD; Richard G. Lester, MD; Barnes Woodhall, MD
[+] Author Affiliations

Read before the session on Therapeutics and Pharmacology of the 116th annual convention of the American Medical Association, Atlantic City, NJ, June 20, 1967.

Reprint requests to Division of Radiobiology, Duke University Medical Center, Durham, NC 27706 (Dr. Sanders)


JAMA. 1968;204(3):241-246. doi:10.1001/jama.1968.03140160051014
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Succinate protection against oxygen toxicity in rats was investigated at oxygen pressures of 5, 7, 9, and 11 atmospheres absolute (atm abs), and compared with protection given by dextrose and malate. Times to convulsions were used for comparison. Dextrose and malate gave no protection. Succinate provided relatively long-term protection at 5 and 7 atm abs oxygen exposures, but showed decreasing protection with increasing pressure. Succinate provided no protection at oxygen pressures of 12 atm abs or higher. A 3:1 sodium succinate:ammonium succinate mixture (0.4M, pH 7.4) solved the problem of alkalosis previously encountered with a sodium succinate solution. The infusion of the 3:1 mixture (6 millimols/kg/hr) in dogs exposed to 5 atm abs oxygen delayed convulsion 5 to 11 times longer than in controls. Intracellular localization and thin layer chromatography studies with succinate-2, 314C showed that succinate readily penetrated the blood brain barrier.

REFERENCES

Bert, P.: Barometric Pressure , M. A. Hitchcock and F. A. Hitchcock (trans.), Columbus, Ohio: Longs College Book Company, 1943;.
Thomas, J.J., Jr.; Neptune, E.M., Jr.; and Sudduth, H.C.:  Toxic Effects of Oxygen at High Pressure on the Metabolism of D-Glucose by Dispersions of Rat Brain , Biochem J 88:31-45 ( (July) ) 1963;.
Dickens, F.:  The Toxic Effects of Oxygen on Brain Mitochondria and on Tissue Enzymes: I. Brain Metabolism, 2. Tissue Enzymes , Biochem J 40:145-187 ( (Jan) ) 1946;.
Kaplan, S.A., and Stein, S.M.:  Effects of Oxygen at High Pressure on the Transport of Potassium and Glutamate in Guinea Pig Cortex , Amer J Physiol 190:157-162 ( (July) ) 1957;.
Sanders, A.P., et al:  Effects of Hyperbaric Oxygenation on Metabolism: I. ATP Concentration in Rat Brain, Liver, and Kidney , Proc Soc Exp Biol Med 121:32-34 ( (Jan) ) 1966;.
Sanders, A.P.; Hall, I.H.; and Woodhall, B.:  Succinate: Protective Agent Against Hyperbaric Oxygen Toxicity , Science 150: 1830-1831 ( (Dec) ) 1965;.
Sanders, A.P., et al: " In Vivo Effects of Hyperbaric Oxygen Toxicity and Succinate as a Preventative ," in Brown, I. W., Jr., and Cox, B.G. (eds.): Proceedings of The Third International Conference on Hyperbaric Medicine , Washington, DC, National Academy of Sciences-National Research Council, publication 1404, 1966;, pp 73-78.

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Bert, P.: Barometric Pressure , M. A. Hitchcock and F. A. Hitchcock (trans.), Columbus, Ohio: Longs College Book Company, 1943;.
Thomas, J.J., Jr.; Neptune, E.M., Jr.; and Sudduth, H.C.:  Toxic Effects of Oxygen at High Pressure on the Metabolism of D-Glucose by Dispersions of Rat Brain , Biochem J 88:31-45 ( (July) ) 1963;.
Dickens, F.:  The Toxic Effects of Oxygen on Brain Mitochondria and on Tissue Enzymes: I. Brain Metabolism, 2. Tissue Enzymes , Biochem J 40:145-187 ( (Jan) ) 1946;.
Kaplan, S.A., and Stein, S.M.:  Effects of Oxygen at High Pressure on the Transport of Potassium and Glutamate in Guinea Pig Cortex , Amer J Physiol 190:157-162 ( (July) ) 1957;.
Sanders, A.P., et al:  Effects of Hyperbaric Oxygenation on Metabolism: I. ATP Concentration in Rat Brain, Liver, and Kidney , Proc Soc Exp Biol Med 121:32-34 ( (Jan) ) 1966;.
Sanders, A.P.; Hall, I.H.; and Woodhall, B.:  Succinate: Protective Agent Against Hyperbaric Oxygen Toxicity , Science 150: 1830-1831 ( (Dec) ) 1965;.
Sanders, A.P., et al: " In Vivo Effects of Hyperbaric Oxygen Toxicity and Succinate as a Preventative ," in Brown, I. W., Jr., and Cox, B.G. (eds.): Proceedings of The Third International Conference on Hyperbaric Medicine , Washington, DC, National Academy of Sciences-National Research Council, publication 1404, 1966;, pp 73-78.
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