Acute fluoride toxicity was induced in anesthetized rats by the continuous iv infusion of fluoride at 1.40 μmol/min. This infusion continued until the death of the animals. Early signs of toxicity, which developed in all animals during the first hour of fluoride infusion, included diuresis, falling urinary osmolality, and glomerular filtration rate at plasma fluoride concentrations of 0.4 to 0.5 mm. The animals were then assigned to three groups. Groups 1, 2, and 3 received intravenous infusions of isotonic saline (control), isotonic sodium bicarbonate, and isotonic sodium bicarbonate plus acetazolamide, respectively. Compared to group 1, groups 2 and 3 survived the high fluoride infusion longer (5.93 vs 7.61 and 10.27 hr, respectively) and tolerated more fluoride (47.8 vs 61.9 and 80.7 mg/kg, respectively). At any given time (dose) after starting the high fluoride infusion, plasma fluoride concentrations were lower and mean arterial blood pressures, glomerular filtration rates, fluoride renal excretions, clearances and fractional clearances, and blood and urine pH values were higher in animals from groups 2 and 3 compared to group 1. Further, group 3 was more resistant to fluoride toxicity than group 2. Terminal tissue-to-plasma fluoride concentrations for heart were lowest in groups 2 and 3 while there were no differences among the groups for brain. It is concluded that metabolic alkalosis can favorably influence the course of a developing episode of acute fluoride toxicity and that this maneuver should be an important addition to the currently accepted therapeutic regimen.
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