de L'importance Relative de la Défaillance Respiratoire et de la Défaillance Cardiaque Dans L'agtion Léthale des Cyanures

Paulet, G

doi:10.3109/13813455509145401

Cited by 9 publications

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“…A method of administration often used (Paulet, 1955a(Paulet, , b, 1960Delga et al, 1961a, b), but not employed in the present investigation, is to anaesthetize the animal and to inject the cyanide intravenously at a constant slow rate of about 0.1 mg/kg/min. The results so obtained do not seem to differ greatly from those of the usual procedure for intravenous injection.…”

Section: Toxicity Of Hydrocyanic Acidmentioning

confidence: 99%

“…Paulet (1955aPaulet ( , b, 1960 (1961a, b) 3.7 Bartelheimer (1962 b) In acute experiments, cobalt salts given intravenously cause a fall, followed by a rise and a later fall, of arterial pressure, an increase in breathing, cramps, vomiting and acute diarrhoea with intestinal inflammation (Stuart, 1884;Le Goff, 1930;Bartelheimer, 1962a;Tauberger & Klimmer, 1963). These effects have been analysed by Bartelheimer (1962a), and by Tauberger & Klimmer (1963), and shown to be partly due to central action and partly to peripheral effects.…”

Section: The Toxicity Of Cobalt Saltsmentioning

confidence: 99%

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Cobalt Compounds as Antidotes for Hydrocyanic Acid

Evans

1964

British Journal of Pharmacology and Chemotherapy

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The antidotal potency of a cobalt salt (acetate), of dicobalt edetate, of hydroxocobalamin and of cobinamide against hydrocyanic acid was examined mainly on mice and rabbits. All the compounds were active antidotes for up to twice the LD50; under some conditions for larger doses. The most successful was cobalt acetate for rabbits (5 x LD50), which was effective at a molar cyanide/cobalt (CN/Co) ratio of 5, but had as a side-effect intense purgation. Hydroxocobalamin was irregular in action, but on the whole was most effective for mice (4.5 X LDS0 at a molar ratio of 1), and had no apparent side effects. Dicobalt edetate, at molar ratios of up to 2, was more effective for rabbits (3 x LD50) than for mice (2 x LD50), but had fewer side effects than cobalt acetate. The effect of thiosulphate was to augment the efficacy of dicobalt edetate and, in mice, that of hydroxocobalamin; but, apparently, in rabbits, to reduce that of hydroxocobalamin. Cobinamide, at a molar ratio of 1, was slightly more effective than hydroxocobalamin on rabbits and also less irregular in its action. Cobalt acetate by mouth was effective against orally administered hydrocyanic acid. The oxygen uptake of the body, reduced by cyanide, is rapidly reinstated when one of the cobalt antidotes has been successfully administered.Hydrocyanic acid acts as a poison because it combines with, and immobilizes the function of, the iron atom in cytochrome oxidase (derived from cytochrome a3) (Keilin & Hartree, 1939), so blocking the electron transfer through the cytochrome system, and checking the final oxidations involving oxygen uptake of the tricarboxylic acid cycle. It also inhibits many other enzymes, for example, decarboxylases (Blaschko, 1942); these last effects have no recognizable relation to the toxic action.Attempts to find an antidote for cyanide have usually been in the direction of breaking down the cyanide-cytochrome a3 complex, and have looked for substances with a stronger affinity for cyanide ions than has the oxidase. One such method is to convert some of the blood haemoglobin into methaemoglobin, for example, by injection of a nitrite (Paulet, 1959); the methaemoglobin combines with the cyanide ion to form the very stable cyanmethaemoglobin. This has the drawback that it involves the loss of oxygen-carrying power of the blood, so that, for example, to antidote twice the LD50 of cyanide would be equivalent to the loss of about 10% (or in an adult man 450 ml.) of the blood.Since cobalt salts form stable complexes with cyanide, the cobaltocyanides, M4Co(CN)6, and the cobalticyanides, M3Co(CN)6, they have been shown long ago

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Section: Toxicity Of Hydrocyanic Acidmentioning

confidence: 99%

Section: The Toxicity Of Cobalt Saltsmentioning

confidence: 99%