A. Royshapira
Nov 1, 1980
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0
Influential Citations
24
Citations
Quality indicators
Journal
Toxicology and Applied Pharmacology
Abstract
Fluoroacetate, which is an inhibitor of the tricarboxilic acid cycle, is widely used as a rodenticide. Fluoroacetate is converted in the body to fluorocitrate, which is an inhibitor of the enzyme aconitate hydrase. As a result, energy production goes down, and citrate accumulates. As citrate is a potent chelator of calcium ion, we postulated that ionized calcium concentration in the blood would drop. Fluoroacetate, 0.03 mmol/kg, was injected iv into anesthetized cats. Ionized calcium concentration in anaerobically drawn arterial blood samples was measured with an ion-exchange electrode. Samples were taken immediately before and 40 min after the poisoning, after which the animals were either used as controls (six cats) or treated with an infusion of iv CaCl2 (another six cats), so as to restore ionized calcium levels to normal values. Forty minutes after fluoroacetate injection, the ionized calcium levels fell by an average of 27.2%, from 1.09 ± 0.07 to 0.79 ± 0.14 mM. There was a corresponding prolongation of the QTc interval of the ECG (r = 0.82). Treatment with CaCl2 significantly prolonged the life of the treated animals as compared to the control animals (p < 0.0016 by the Mann-Whitney rank sum test). Our findings suggest that reduced levels of ionized calcium play an important role in the pathogenesis of fluoroacetate poisoning. The reduced levels of Ca2+ are an adequate explanation for the toxic effects of fluoroacetate, and may be the missing link between the biochemistry of the poisoning and the clinical manifestations.