Methemoglobin cyanide

Figure 8.48 Mossbauer spectrum of human methemoglobin cyanide...

The automated method differs from the ICSH method chiefly in that oxidation and ligation of heme iron occur after the hemes have been released from globin. Therefore, ferricyanide and cyanide need not diffuse into the hemoglobin and methemoglobin, respectively. Because diffusion is rate-limiting in this reaction sequence, the overall reaction time is reduced from approximately three minutes for the manual method to 3 —15 seconds for the automated method. Reaction sequences in the Coulter S + II and the Technicon H 1 and H 2 are similar. Moreover, similar reactions are used in the other Coulter systems and in the TOA and Unipath instmments. 

The purpose of sodium nitrite (or amyl nitrite in the absence of IV access) is to produce methemoglobin, which binds cyanide with greater affinity than mitochondrial cytochromes. In the presence of decreased oxygen carrying capacity, as in combined exposures to cyanide and carbon monoxide (e.g., some fires), sodium nitrite can be detrimental and should be avoided. 

Smith L, Kruszyna H, Smith RP. 1977. The effect of methemoglobin on the inhibition of cytochrome c oxidase by cyanide, sulfide or azide. Biochem Pharmacol 26 2247-2250. 

Taurog et al. [216] showed that contrary to previous suggestions, both iodination and coupling are catalyzed by the oxoferryl porphyrin Tr-cation radical of TPO Compound I and not the oxoferryl protein radical. HRP catalyzed the oxidation of bisulfite to sulfate with the intermediate formation of sulfur trioxide radical anion S03 [217] HPO, MPO, LPO, chloroperoxidase, NADH peroxidase, and methemoglobin oxidized cyanide to cyanyl radical [218],... 

HCN in the blood is almost completely contained in the red blood cells where it is bound to methemoglobin. Immediately after infusion of sodium nitroprusside into patients, 98.4% of the blood cyanide was found in the red blood cells (Vesey et al. 1976). At normal physiological levels of body methemoglobin (0.25% to 1% of the hemoglobin), a human adult can bind about 10 mg of HCN (Schulz 1984). 

In addition to binding to cytochrome c oxidase, cyanide inhibits catalase, peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, and succinic dehydrogenase activities. These reactions may make contributions to the signs of cyanide toxicity (Ardelt et al. 1989 Rieders 1971). Signs of cyanide intoxication include an initial hyperpnea followed by dyspnea and then convulsions (Rieders 1971 Way 1984). These effects are due to initial stimulation of carotid and aortic bodies and effects on the central nervous system. Death is caused by respiratory collapse resulting from central nervous system toxicity. 

Sun et al. (1995) reported that the nitric oxide generator, isosorbide dinitrate, is an effective cyanide antidote in mice. They showed that the mechanism does not involve methemoglobin formation and suggested that nitric oxide might antagonize the respiratory depressant effects of cyanide. Other more efficient nitric oxide generators may be very useful cyanide antidotes. 

Blood Separation in a microdiffusion cell absorption in methemoglobin solution Spectrophotometric (free cyanide determination) 0.4 pg/mL 80 Tomoda and Hashimoto 1991... 

Cyanide in biological tissue and fluids can be measured spectrophotometrically after reaction with methemoglobin (Tomoda and Hashimoto 1991). The detection limit is 0.4 pg/mL. Other performance data were not reported (Tomoda and Hashimoto 1991). Cyanide in urine has been determined using microdiffusion separation and colorimetric determination (Brimer and Rosling 1991). Detection limits are in the ng/L range other performance data were not reported (Brimer and Rosling 1991). 

Waste water Addition of sample to buffered methemoglobin Spectrophotometry (free cyanide) 0.2 pg/mL No data Tomoda and Hashimoto 1991... 

DiPalma JR. 1971. Noxious gases and vapors I. Carbon monoxide, cyanides, methemoglobin, and sulfhemoglobin. In Drill s pharmacology in medicine. McGraw-Hill Book Co., New York, NY. pp.l 189-1205. 

Kirk M, Kulig K, Rumack BH. 1989. Methemoglobin and cyanide kinetics in smoke inhalation [Abstract]. Vet Hum Toxicol 31 353. 

Scharf BA, Fricke RF, Baskin SI. 1992. Comparison of methemoglobin formers in protection against the toxic effects of cyanide. Gen Pharmacol 23(1) 19-25. 

Tomoda A, Hashimoto K. 1991. The determination of cyanide i water and biological tissues by methemoglobin. J Hazardous Materials 28 241-249. 

Tomoda A, Nagai K, Hashimoto K. 1992. A simple and convenient method for the determination of cyanide in bloods and water by methemoglobin. Int Congr Ser - Excerpta Med 991 (Progress in Clinical Biochemistry) 789-791. 

Nitrites may be used as an antidote for cyanide poisoning if given rapidly. They convert hemoglobin to methemoglobin, which binds cyanide in the blood before reaching the tissues. Oxygen is also given if possible. 

Finally, it should be mentioned that HA is effective as an antidote against cyanide poisoning by virtue of converting ca 20% of the hemoglobin to methemoglobin. This will be discussed at length in Section ILF. 

Cyanide Sodium nitrate Forms methemoglobin, which binds cyanide, thus removing it from... 

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