Ethard W. Van Stee

Short-term inhalation exposure to bromotrifluoromethane

Abstract Exposure of dogs and monkeys to 10–80% bromotrifluoromethane (CBrF 3 ) caused cardiovascular and central nervous system effects which increased in severity with increasing CBrF 3 concentration. An initial fall in mean arterial blood pressure of 10–20 mm Hg at the lower CBrF 3 concentrations and 40–60 mm Hg at the higher CBrF 3 concentrations was observed. Most animals developed spontaneous cardiac arrhythmias within 1–3 min of exposure to 40% or more CBrF 3 . Arrhythmias could be produced in those animals not developing arrhythmias spontaneously by the intravenous injection of a pressor dose of epinephrine. Larger doses of epinephrine (5–10 μg/kg) caused ventricular fibrillation with cardiac arrest in dogs and, commonly, spontaneous defibrillation in monkeys. Epileptiform convulsions were seen in about 50% of the dogs exposed to 50–80% CBrF 3 while conscious. Conscious monkeys, on the other hand, became lethargic, and no convulsions were seen.

The mechanism of the peripheral vascular resistance change during exposure of dogs to bromotrifluoromethane.

Abstract Thirtytwo male beagle dogs were used in 16 cross-circulation experiments wherein arterial blood from one dog (donor) was perfused at constant flow rate through a hind limb (HL) of another dog (recipient). The HL innervation remained intact. Exposure of the donor to 67–70% CBrF 3 was accompanied by a reversible decrease in the donors mean arterial blood pressure. The HL perfusion pressure (and therefore vascular resistance in HL) was unaltered. Exposure of the recipient to 67–70% CBrF 3 was accompanied by a reversible decrease in the recipient mean arterial blood pressure and HL perfusion pressure. The HL perfusion pressure change was greatly attenuated by pretreatment of the HL with phenoxybenzamine and abolished by pretreatment of the recipient with hexamethonium. Nictitating membrane tension and vagal inhibition of the heart in response to electrical stimulation of the corresponding cut ends of the vagosympathetic trunks were measured in 5 dogs before, during and after exposure to 80% CBrF 3 . The CBrF 3 exposure was accompanied by a reversible decrease in both nictitating membrane tension and vagal inhibition of the heart. The mechanism of the decrease in mean arterial blood pressure during CBrF 3 exposure was concluded to be a decrease in vasomotor tone resulting from ganglionic blockade. No direct vascular smooth muscle effect of CBrF 3 was observed.

The determination of the inotropic effect of exposure of dogs to bromotrifluoromethane and bromochlorodifluoromethane

Seventeen beagle dogs representing both sexes and weighing an average of 10 kg each were used in open-chest experiments. The dogs were anesthetized by the continuous iv infusion of a mixture of 10% ethanol and 60 mg/liter morphine sulfate in 5% glucose in water. Left ventricular pressure was monitored through a metal cannula inserted through the left ventricular free wall following a left-side thoractomy. Left ventricular pressure was used to control the horizontal deflection and dPdt was used to control the vertical deflection of a vector oscilloscope. Peak dPdt÷P was calculated from the Lissajous figures generated, and provided an index of the inotropic state of the left ventricular myocardium. The method was validated using isoproterenol and propranolol, known inotropic agents. Since CBrF3 and CBrClF2 cause changes in mean arterial pressure, the effects of variable afterload on peak dPdt÷P were determined by aortic constriction. Both fluoroalkanes were demonstrated to produce concentration-dependent decreases in peak dPdt÷P that reflected decreased mycocardial contractility.

Effect of dibromotetrafluoroethane inhalation on hepatic drug metabolism in mice.

Abstract Inhalation of dibromotetrafluoroethane, 0.63 to 1.0%, for 5 hr daily, for 3 or 4 days, reduced hexobarbital sleeping time and zoxazolamine paralysis time 2-fold in mice. Increased metabolism of hexobarbital and zoxazolamine by the hepatic 9000 g microsomal supernatant fraction prepared from exposed mice correlated well with the effects determined in vivo. Addition of 2,4-dichloro-6-phenyl-phenoxyethyldiethylamine (SKF 525-A) to the hepatic 9000 g microsomal supernatant fraction prevented the dibromotetrafluoroethane-induced increase in hepatic drug metabolism.