The mechanism of sodium-fluoride (7681494) cardiovascular toxicity was examined. Spontaneously breathing or mechanically ventilated male Wistar-rats instrumented with carotid and aorta arterial transducers and thermistors were infused intravenously with 2mg/kg per minute (min) sodium-fluoride until death. Arterial blood pressure, heart rate, cardiac output, peripheral resistance, respiration frequency, oxygen consumption (VO2), carbon-dioxide production, the respiratory quotient (RQ), and serum calcium, calcium ion (Ca+2), and fluoride ion concentrations were measured. Some rats were also infused with calcium-chloride. Hearts were removed from untreated male Wistar-rats. The left atria or whole hearts were perfused with up to 30 micromolar sodium-fluoride. The effects on contractile force of the preparations were determined. In spontaneously breathing rats, sodium-fluoride caused rapid progressive decreases in mean arterial pressure, heart rate, cardiac output, and peripheral resistance. A significant increase in breathing frequency occurred during the first 20min of infusion. This led to a significant increase in VO2 and a decrease in carbon-dioxide production. Total body VO2 was significantly decreased and the RQ was significantly decreased after 30min. Death occurred as a result of atrioventricular block and cardiac asystole after 39.8min infusion. This corresponded to an acute lethal dose of 79.6mg/kg sodium-fluoride. Mechanical ventilation did not significantly or consistently alter the cardiovascular response to sodium-fluoride. The acute lethal dose was 88.6mg/kg sodium-fluoride, similar to that for spontaneously breathing rats. Serum calcium and Ca+2 concentration was decreased by sodium-fluoride infusion. Simultaneous infusion of calcium-chloride did not present sodium-fluoride induced cardiovascular failure, but increased the time to death to 46.5min and the acute lethal dose to 93mg/kg sodium-fluoride. The serum fluoride concentration was decreased. Sodium-fluoride caused a dose dependent decrease in contractile force in the isolated atria and perfused heart preparations. The authors conclude that the lethal outcome of sodium-fluoride intoxication is due to cardiodepression and vasodilation.