PHARMACOLOGY AND CHEMISTRY OF SUBSTANCES WITH CARDIAC ACTIVITY

II. EFFECT OF l-ASCORBIC ACID AND SOME RELATED COMPOUNDS AND OF HYDROGEN PEROXIDE ON THE ISOLATED HEART OF THE FROG

¹ From the Department of Pharmacology, Harvard Medical School, Boston, and The Converse Laboratory of the Department of Chemistry, Harvard University, Cambridge

l-Ascorbic acid or d-iso-ascorbic acid, when administered continuously to the isolated frog heart in an initial concentration of 1:10,000, led to an increase in the height of contraction and an inconsistent increase in rate, and caused irreversible systolic standstill within 1 to 2 hours. Our experiments indicate that the effect upon the frog heart was not due to l-ascorbic acid or d-iso-ascorbic acid itself, nor to their products of dehydrogenation, the corresponding dehydroascorbic acids. The effect was absent when the ascorbic acids were protected against the dehydrogenation by excluding oxygen from the solution, or, in the case of l-ascorbic acid, by introducing methyl groups into the hydroxyl groups of the lactone ring to form the dimethyl ascorbic acid. During the process of dehydrogenation of l-ascorbic acid or d-iso-ascorbic acid 1:10,000 in bicarbonate buffer solution, hydrogen peroxide appeared in the solutions and was found to reach concentrations of the range of 1:200,000 to 1:100,000 under the conditions of our experiments. Evidence is presented which indicates that the characteristic action of l-ascorbic acid and of d-iso-ascorbic acid solutions upon the frog heart can be accounted for by these concentrations of hydrogen peroxide.