Abstract

Methylene blue is employed therapeutically in the management of acute, acquired methemoglobinemia to accelerate reductive processes in the red cell. In normal humans or laboratory animals, however, controversy has existed for many years about the paradoxical ability of methylene blue to generate low levels of methemoglobin. Under physiological conditions human red cells maintain an equilibrium between methemoglobin and hemoglobin which favors the latter to the extent of 95 to 98%. Results presented here confirm that methylene blue accelerates the rate of hemoglobin-methemoglobin turnover with only minor shifts in the equilibrium of the reaction. This accelerated turnover does not contribute significantly to the steady-state oxygen consumption of red cells exposed to methylene blue. The latter is partially blocked by N-ethylmaleimide whereas the oxygen consumption of red cells in the absence of methylene blue is inhibited by high concentrations of cyanide. Under artificial conditions in vitro methylene blue can significantly alter the equilibrium between hemoglobin and methemoglobin to greatly favor the latter. In order of decreasing importance, factors which favor methemoglobin formation by methylene blue include: hemolysis, low oxygen tensions and illumination. Factors which favor methemoglobin reduction include: intact red cells and low oxygen tensions. Both methemoglobin formation and methemoglobin reduction by methylene blue are concentration-dependent phenomena, and the stoichiometry of the reactions indicate that in either case the dye is recycled many times.