Acute cardiovascular toxic effects of copper in anesthetized rabbits

Copper deficiency is linked to many types of cardiovascular diseases. Copper toxicity may not be common, but it produces cardiac problems and even lethality. However, little is known about the precise mechanism of cardiotoxic action of copper in mammals. In an effort to characterize the cardiovascular effects and potential toxic action of copper, white New Zealand rabbits were instrumented for the measurement of cardiovascular parameters under urethane anesthesia. Left ventricular pressure and its dP/dt as well as the sympathetic efferent renal nerve activity were also monitored continuously before, during and after the injection of various doses of copper. Low doses of copper (3 mg/kg or less) increased blood pressure with a slight reduction in heart rate. There was also a transient increase in cardiac contractile force as shown by an increase of dP/dt with a reduction in sympathetic renal efferent nerve activity. However, high doses of copper (10 mg/kg or higher) decreased these cardiac parameters, which led to a state of shock, 90 seconds after the copper treatment. There was a compensatory increase in respiration rate and renal nerve activity during the shock. Thus, the data suggest that copper initially activates peripheral organs such as the heart and subsequently produces a distinct inhibitory action on sympathetic outflow, which is related to the toxic action of this metal.