PROTECTIVE EFFECT OF STROMA-FREE METHEMOGLOBIN DURING CYANIDE POISONING IN DOGS

Background: During fire exposure, cyanide toxicity can block aerobic m etabolism. Oxygen and sodium thiosulfate are accepted therapy, However , nitrite-induced methemoglobinemia, which avidly binds cyanide, decre ases oxygen-carrying capacity that is already reduced by the presence of carboxyhemoglobin (inhalation of carbon monoxide in smoke). This st udy tested whether exogenous stroma-free methemoglobin (SFmetHb) can p revent depression of hemodynamics and metabolism during canine cyanide poisoning, Methods: In 10 dogs (weighing 18.8 +/- 3.5 kg) anesthetize d with chloralose-urethane and mechanically ventilated with air, basel ine hemodynamic and metabolic measurements were made. Then, 137 +/- 31 ml of 12 g% SFmetHb was infused into five dogs (SFmetHb group), Final ly, the SFmetHb group and the control group (n = 5, no SFmetHb) receiv ed an intravenous potassium cyanide infusion (0.072 mg . kg(-1). min(- 1)) for 20 min. Oxygen consumption (Vover dot(O2)) measured with a Dat ex Deltatrac (Datex Instruments, Helsinki, Finland) metabolic monitor and cardiac output (Qover dotT) was measured by pulmonary artery therm odilution, Results: From baseline to cyanide infusion in the control g roup, QT decreased significantly (p < 0.05) from 2.9 +/- 0.8 to 1.5 +/ - 0.4 l/min, mixed venous P-CO2 (P (V) over bar(CO2)) tended to decrea se from 35 +/- 4 to 23 +/- 2 mmHg, P (V) over bar(O2) increased from 4 3 +/- 4 to 62 +/- 8 mmHg, Vover dot(O2) decreased from 93 +/- 8 to 64 +/- 19 ml/min, and lactate increased from 2.3 +/- 0.5 to 7.1 +/- 0.7 m M. In the SFmetHb group, cyanide infusion did not significantly change these variables. From baseline to infused cyanide, the increases in b lood cyanide (4.8 +/- 1.0 to 452 +/- 97 mu M) and plasma thiocyanate c yanide (18 +/- 5 to 65 +/- 22 mu M) in the SFmetHb group were signific antly greater than those increases in the control group. SFmetHb itsel f caused no physiologic changes, except small decreases in heart rate and P (V) over bar(O2). Peak SFmetHb reached 7.7 +/- 1.0% of total hem oglobin, Conclusions: Prophylactic intravenous SFmetHb preserved cardi ovascular and metabolic function in dogs exposed to significant intrav enous cyanide. Blood concentrations of cyanide, and its metabolite, th iocyanate, revealed that SFmetHb trapped significant cyanide in blood before tissue penetration.