Interaction between ethyl methylene blue and cyanide-induced increases in blood lactate

Previous workers have reported that ethyl methylene blue (EMB) diminishes cyanide-induced increases in blood lactate (CIL); the present study investigates the mechanism underlying this interaction. Accordingly, sodium cyanide (1.2 mg./Kg.) was infused into the abdominal aorta of anesthetized, spontaneously breathing dogs. Following cyanide infusion, arterial lactate concentration increased 5.4 +/- 1.1 mmol./L. and arterial PCO2 decreased 22 +/- 3 mm. Hg. A second group of dogs was pretreated with EMB (8 to 15 mg./Kg.); this dose of EMB elicited twofold increments in oxygen consumption and induced the formation in vivo of methemoglobin (0.8 +/- 0.1 gm./100 ml.). Following cyanide infusion, the increase in lactate in EMB animals was only 0.6 +/- 0.2 mmol./L.; the decrease in arterial PCO2 was limited to 5 +/- 1 mm. Hg. In order to clarify the relationship between cyanide-induced hypocapnia and CIL, cyanide was infused into a third group of dogs that were maintained isocapneic via mechanical ventilation; despite constancy of arterial PCO2, lactate increased 6.0 +/- 0.7 mmol./L. To determine the effect of EMB-induced tissue hypermetabolism on CIL, twofold increments in oxygen consumption were produced in a fourth group of dogs by pretreatment with sodium salicylate. Following cyanide infusion, salicylate-pretreated animals increased lactate 7.2 +/- 1.2 mmol./L. In order to assess the relationship between EMB-induced methemoglobinemia and the decrease in CIL, similar concentrations of methemoglobin were produced in two subsequent groups of dogs by two different techniques (i.e., by aniline pretreatment or by infusion of methemoglobinemic blood that had been prepared in vitro by addition of sodium nitrite). CIL in these animals was again markedly diminished (i.e., increments of only 0.6 +/- 0.3 mmol./L.) It is concluded that EMB diminishes CIL by a mechanism other than elimination of cyanide-induced hypocapnia or induction of tissue hypermetabolism. The results suggest that methemoglobin formation may completely account for the ability of EMB to effect a decrement in CIL.