In vitro demonstration of the antidotal efficacy of hydroxocobalamin in cyanide poisoning.
The effects of sodium cyanide (1 mM) and the antidotal action of hydroxocobalamin (1 mM) were studied on rat cardiac papillary muscle. A 10-min period of exposure to cyanide induced a marked decrease in inotropy as shown by a decrease in the maximum unloaded shortening velocity (Vmax: 64 +/- 11% of precyanide values, p <0.01) and active isometric force (AF/s: 35 +/- 13%, p <0.01). The impairment of contraction-relaxation coupling under low load and the nearly complete disappearance of the load sensitivity of relaxation suggested a decrease in sarcoplasmic reticulum function. The proportional acceleration in isometric relaxation suggested a decrease in myofilament calcium sensitivity. There was a nearly complete recovery from cyanide poisoning after 5 min of exposure to hydroxocobalamin, whereas in a control group receiving cyanide alone, the mechanical parameters remained unchanged or were further impaired. The effects of hydroxocobalamin developed very quickly, beat to beat. The main toxic target of cyanide is brain and heart cytochrome oxidase, and brain damage appears only a few minutes after the onset of anoxia. Because hydroxocobalamin is a rapid and powerful antidote, it may be useful in the treatment of acute cyanide poisoning.
Riou
B
B
Institut National de la Santé et de la Recherche Médicale U275, LOA-ENSTA-Ecole Polytechnique, Palaiseau, France.
Baud
F J
FJ
Astier
A
A
Barriot
P
P
Lecarpentier
Y
Y