Abstract

Methemoglobin does not accumulate in significant quantities in the blood of dogs after intravenous injection of clinically recommended quantities of methylene blue. This fact, however, should not bring into question the proposed methemoglobin explanation of the dye's action in cyanide poisoning. The failure of methemoglobin to accumulate is explicable on the basis of the known behavior of the reactions involved, namely, the reduction of the formed methemoglobin by leuco-methylene blue and the enzyme systems present in the erythrocytes, and the rapid disappearance of the injected dye from the blood. In vivo formation of methemoglobin is readily demonstrable after administration of both cyanide and methylene blue because of the stability of the cyanmethemoglobin which is formed. Considerably more than half of 2 m.l.d. of subcutaneously administered cyanide is demonstrably bound in the circulating erythrocytes of dogs injected with methylene blue immediately before administration of the cyanide. When the dye is injected continuously throughout the period of cyanide absorption a still greater fraction of the cyanide is bound in the blood. The principal action of methylene blue in counteracting the toxic effects of cyanide appears to depend, therefore, upon methemoglobin formation. In the absence of experimental demonstration that methylene blue can replace the cyanide sensitive catalysts which are concerned with vital processes the methemoglobin explanation appears to be all that is required.