Alex Azar

Blood Levels of Fluorocarbon Related to Cardiac Sensitization

Unanesthetized beagle dogs were exposed to concentrations of fluorocarbon-11 and fluorocarbon-12 which had been reported to produce cardiac sensitization. During and after the exposure, arterial and venous blood samples were obtained for fluorocarbon analysis. The blood concentration rose rapidly during the first few minutes of the 10-minute exposure and more slowly thereafter. When the exposure was terminated, there was a rapid initial fall in the blood concentration followed by a more prolonged decline. A definite arterial-venous difference was found. Despite a tenfold difference in the inspired concentration of the two compounds, the blood concentrations associated with cardiac sensitization were similar for both agents. The average blood concentration (µg/ ml) associated with exposure to levels known to sensitize the beagle heart was: 28.6 arterial and 19.7 venous for fluorocarbon-11; and 35.3 arterial and 22.8 venous for flurocarbon-12.

Halogenated Hydrocarbon-Induced Cardiac Arrhythmias Associated with Release of Endogenous Epinephrine

Many unsubstituted and halogenated hydrocarbons have been shown to be capable of sensitizing the mammalian heart to intravenously injected epinephrine, resulting in serious and sometimes fatal cardiac arrhythmias. This experiment was performed to determine if cardiac sensitization could occur in animals in the absence of an exogenous source of epinephrine, as this phenomenon has been alleged to cause sudden deaths in humans in the absence of exogenous epinephrine. Beagle dogs were trained to run on a treadmill to increase their circulating level of epinephrine. While being exercised, they were exposed to fluorocarbon 11, fluorocarbon 12, or fluorocarbon 114, which had been tested previously at Haskell Laboratory and found to be capable of sensitizing the dogs heart to intravenousty injected epinephrine. The results of this study show that, while fluorocarbon 12 and fluorocarbon 114 did produce cardiac sensitization, a much higher concentration was needed to produce this effect than with the intravenous a...

Experimental Human Exposures to Fluorocardon 12 (Dichlorodifluoromethane)

The acute toxicity of fluorocarbon 12 was studied as it relates to establishing safe hygienic standards for single, brief exposures. Two human volunteers were exposed to concentrations of 1000 and 10,000 ppm of fluorocarbon 12 for 2.5 hours. They were exposed twice to both concentrations, and on six occasions they were exposed to air. Clinical observations, laboratory tests, subjective impressions, continuous electrocardiogram monitoring, and tests of psychomotor performance did not reveal any adverse effects resulting from exposure to 1000 ppm of fluorocarbon 12. Exposures to 10,000 ppm resulted only in a 7% reduction in the standardized psychomotor test score. These findings suggest that exposure to 10,000 ppm of fluorocarbon 12 for 2.5 hours will not pose a serious threat to an individuals health. Measurement of the subjects’ end-tidal air for fluorocarbon 12 made immediately postexposure and periodically thereafter showed that the compound is rapidly eliminated from the lungs.

Effect of Lead on Blood Regeneration Following Acute Hemorrhage in Dogs

Thirty-six beagle dogs were divided into three hematologically similar groups of six males and six females each. The dogs of one group acted as controls and were fed only the basic diet. The dogs of the other two groups had lead acetate added to their diets, those of one group receiving 100 ppm of lead by weight, those of the other group, 500 ppm for 30 weeks followed by 1000 ppm for 16 weeks. By the end of 46 weeks, both lead-treated groups had accumulated burdens of lead as demonstrated by increases in blood and urine lead concentrations, increased urine δ-aminolevulinic acid excretion, and decreased red cell ALA dehydrase activity. At this time a two-step withdrawal of one-half the estimated blood volume from each dog resulted in a 30 to 40% reduction in hemoglobin concentration, red cell count, and hematocrit ratio. The recoveiy curves of the hemoglobin concentration, red cell count, and hematocrit ratio were not affected by the presence of the lead.

Recovery of Blood Lead Concentration and of Red Cell 8-Aminolevulinic Acid Dehydrase Activity in Dogs Following Return to Normal Diets after 75 Weeks of Lead Feeding

Blood lead concentration and red cell delta-aminolevulinic acid dehydrase (ALAD) activity were determined at intervals for eight months after symptom-free dogs, which had received 100 ppm or 500-1000 ppm of lead, by weight, in their diets for 75 1/2 weeks, were returned to a lead-free diet. Statistical treatment of the data disclosed a linear relationship between the logarithm of blood lead concentration or of ALAD activity and the logarithm of time (experimental week) during the recovery period. The calculated regressions predict that recovery of ALAD will occur before recovery of the blood lead concentration. Predicted recovery times depend on the levels selected as those which must be attained for recovery to be complete, as well as on the dosage of lead. The logarithm of the slope of the ALAD recovery regression of the individual dog has a linear relation to the percentage reduction in ALAD due to the lead, the regression accounting for 92% of the variance in the recovery rates. The slope of the blood lead recovery regression has a linear relation to the increase in blood lead for the dogs which received the low lead diet, but not for those which received the high lead diet.