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.