The Normal Rate of Reduction of Methemoglobin in Dogs*

Methemoglobin is not present in spectroscopically detectable amounts’ in freshly drawn blood of normal animals of the following and, presumably, other mammalian species: human, dog, cat, rabbit, rat, mouse, horse, monkey (Macacus rhesus), cattle, swine. Furthermore, methemoglobin is not demonstrable in incubated sterile blood from normal animals of these species for many hours after removal from the body. The lag in accumulation of methemoglobin in drawn blood was shown by Warburg, Kubowitz, and Christian (4) to be due to intrinsic enzyme systems of the erythrocytes which reduce methemoglobin to hemoglobin. These workers found that the reducing agents acting in vitro are formed primarily from glucose by the erythrocytes. Lactic acid, activated by an intraerythrocytic enzyme system, accounts for 25 to 50 per cent of the reduction (5). Other reductants have not been identified. One objective of the experiments reported in this paper was to determine the extent to which the enzyme systems contained within the blood account for in vivo reduction of methemoglobin and, thus, for maintenance of the circulating hemoglobin in a functionally active form. Before this was undertaken, it was considered advisable to ascertain the normal physiological rate of methemoglobin reduction in vivo and the influence upon this rate of several physical and chemical factors. Incident to these studies we have determined the course of methemoglobin accumulation and disappearance following administration of a number of recognized methemo-