The pathophysiological profile of the acute cardiovascular toxicity of sodium fluoride.
The intravenous infusion of sodium fluoride (2 mg/kg X min) into anesthetized rats caused a progressive fall in arterial blood pressure, cardiac output, heart rate and peripheral resistance. Respiratory rate increased during the first 20 min of infusion resulting in increased oxygen and decreased carbon dioxide blood concentrations. Total body oxygen consumption decreased after 30 min of NaF infusion by 29%, whereas the respiratory quotient (RQ) increased from 0.8 to 1.06. Death occurred after a mean dose of 79.6 +/- 4.6 mg/kg NaF. The terminal cardiac event before death was atrioventricular block followed immediately by asystole. Artificial ventilation did not influence the cardiovascular and the lethal effects of fluoride infusion. The plasma concentrations of total and ionized calcium decreased upon NaF infusion. The infusion of extra calcium did not prevent NaF-induced cardiovascular failure but decreased plasma fluoride levels and increased the lethal dose of NaF by 17% (not significant). In isolated atria and perfused hearts in vitro, NaF decreased the force of contraction in a dose-dependent manner. In conclusion, cardiovascular failure resulting from the direct cardiodepressive and vasodilatating effects of fluoride (and not from respiratory depression or hypocalcemia) accounts for the lethal outcome of fluoride intoxication.
D000818:Animals; D002118:Calcium / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D006327:Heart Block / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects; D012121:Respiration, Artificial; D012969:Sodium Fluoride / Q000633:toxicity*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D012969:Sodium Fluoride; D002118:Calcium