Comparison of cobinamide to hydroxocobalamin in reversing cyanide physiologic effects in rabbits using diffuse optical spectroscopy monitoring

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Abstract

Our purpose is to compare cobinamide to hydroxocobalamin in reversing cyanide (CN)-induced physiologic effects in an animal model using diffuse optical spectroscopy (DOS). Cyanide poisoning is a major threat worldwide. Cobinamide is a novel molecule that can bind two molecules of cyanide, has a much higher binding affinity than hydroxocobalamin, and is more water soluble. We investigated the ability of equimolar doses of cobinamide and hydroxocobalamin to reverse the effects of cyanide exposure in an animal model monitored continuously by DOS. Cyanide toxicity was induced in 16 New Zealand white rabbits by intravenous infusion. Animals were divided into three groups: controls (n=5) received saline following cyanide, hydroxocobalamin (N=6) following cyanide, and cobinamide (N=5) following cyanide. Cobinamide caused significantly faster and more complete recovery of oxy- and deoxyhemoglobin concentrations in cyanide-exposed animals than hydroxocobalamin- or saline-treated animals, with a recovery time constant of 13.8+/-7.1 min compared to 75.4+/-25.1 and 76.4+/-42.7 min, for hydroxocobalamin- and saline-treated animals, respectively (p<0.0001). This study indicates that cobinamide more rapidly and completely reverses the physiologic effects of cyanide than equimolar doses of cobalamin at the dose used in this study, and CN effects and response can be followed noninvasively using DOS.

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Albert Cerussi, Christopher Jakubowski, B Tromberg … (2000)

A technique for measuring broadband near-infrared absorption spectra of turbid media that uses a combination of frequency-domain (FD) and steady-state (SS) reflectance methods is presented. Most of the wavelength coverage is provided by a white-light SS measurement, whereas the FD data are acquired at a few selected wavelengths. Coefficients of absorption (mu(a)) and reduced scattering (mu(s)') derived from the FD data are used to calibrate the intensity of the SS measurements and to estimate mu(s)' at all wavelengths in the spectral window of interest. After these steps are performed, one can determine mu(a) by comparing the SS reflectance values with the predictions of diffusion theory, wavelength by wavelength. Absorption spectra of a turbid phantom and of human breast tissue in vivo, derived with the combined SSFD technique, agree well with expected reference values. All measurements can be performed at a single source-detector separation distance, reducing the variations in sampling volume that exist in multidistance methods. The technique uses relatively inexpensive light sources and detectors and is easily implemented on an existing multiwavelength FD system.

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Broad bandwidth frequency domain instrument for quantitative tissue optical spectroscopy

Eric Anderson, Olivier Coquoz, Joshua Fishkin … (2000)

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Cyanide poisoning and its treatment.

Clarisa R Gracia, Theodore G. Shepherd (2004)

Cyanide is both widely available and easily accessible throughout the world. Although the compound is not frequently encountered, it has been used as a poison and contaminant in the past and is a potential terrorist agent. Cyanide has the ability to cause significant social disruption and demands special attention to public health preparedness. It can be obtained from a variety of sources, including industrial, medical, and even common household products. Another frequently encountered source of cyanide exposure is residential fires. Exposure to high concentrations of the chemical can result in death within seconds to minutes. Long-term effects from cyanide exposure can cause significant morbidity. The only treatment for cyanide toxicity approved for use in the United States is a kit consisting of amyl nitrite, sodium nitrite, and sodium thiosulfate. Future research aims to find a faster-acting, more effective, and better tolerated treatment for cyanide toxicity.