Methemoglobin and Methylene Blue as Cyanide Antagonists

Abstract

The action of methylene blue in restoring the respiration of cyanide inhibited tissues (Gerard 1 ) has led to the clinical and apparently successful use of the dye as an antidote for cyanide poisoning (Brooks 2 ). It has been urged that methylene blue acts in the intact organism not directly by substituting in the cells for the inactivated respiratory enzymes, but indirectly by removing the cyanide and releasing the enzyme. Cyanide would thus be removed by the formation of the stable cyanmethemoglobin, from it and methemoglobin; formed in turn from the blood pigment by methylene blue (Wendel 3 ). An antagonism of methemoglobin and cyanide has been demonstrated on rat tissues (Rosenthal and Voegtlin 4 ).

It seemed of interest, in this connection, to determine the action of methemoglobin and methylene blue, with cyanide, on isolated invertebrate tissues. Ciliated gill tissue of the quahog (Venus mercenaria) was isolated in sea water and its oxygen consumption followed at 22°C. in Warburg manometers. Alkali in the inset, by absorbing CO₂ and HCN, led to a rise in pH, but always less than 0.5.

The normal Qo₂ (cmm. O₂ per hour per gm. fresh weight) averaged 375 (26 experiments) during the first hour in sea water, about 10% less for the second. Cyanide led to typical inhibition, though rather high concentration was needed. As per cent of the normal, average (4 series of experiments) values in cyanide were : M/11,000, 66; M/5500, 58; M/1100, 56; M/550, 55; M/110, 16. Methylene blue in 0.09% (M/350) concentration, increased the respiration in sea water by one-third. (One-tenth this concentration was without effect, even after cyanide.) Respiration inhibited by M/110 cyanide to 16% normal was more than doubled (to 38%) by the dye, though still depressed. This dye concentration did, however, accurately restore to normal the respiration inhibited (to 57%) by M/1100 cyanide (4 experiments). It is to be noted that considerable restoration occurred even when the added dye was of lower molarity than the cyanide, indicating its separate action as a substitute catalyst in the cell.