title: Comparison of cobinamide to hydroxocobalamin in reversing cyanide physiologic effects in rabbits using diffuse optical spectroscopy monitoring.
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.
authors.affiliation: University of California, Beckman Laser Institute, Irvine, California 92612-1475, USA. mbrenner@uci.edu
authors.forename: Matthew
authors.initials: M
authors.lastname: Brenner
authors.forename: Sari B
authors.initials: SB
authors.lastname: Mahon
authors.forename: Jangwoen
authors.initials: J
authors.lastname: Lee
authors.forename: Jae
authors.initials: J
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Mukai
authors.forename: Seth
authors.initials: S
authors.lastname: Goodman
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Kreuter
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ahdout
authors.forename: Othman
authors.initials: O
authors.lastname: Mohammad
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Sharma
authors.forename: William
authors.initials: W
authors.lastname: Blackledge
authors.forename: Gerry R
authors.initials: GR
authors.lastname: Boss
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000931:Antidotes / Q000737:chemistry / Q000494:pharmacology*; D003038:Cobamides / Q000737:chemistry / Q000494:pharmacology*; D003486:Cyanides / Q000097:blood / Q000633:toxicity*; D006454:Hemoglobins / Q000032:analysis; D006879:Hydroxocobalamin / Q000737:chemistry / Q000494:pharmacology*; D055095:Optics and Photonics; D010108:Oxyhemoglobins / Q000032:analysis; D011817:Rabbits; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D000931:Antidotes; D003038:Cobamides; D003486:Cyanides; D006454:Hemoglobins; D010108:Oxyhemoglobins; C017142:cobinamide; C100003:deoxyhemoglobin; D006879:Hydroxocobalamin