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Biomedical subjects

V Fiserova-Bergerova

Publications and source records attributed to V Fiserova-Bergerova.

11 recordsLinked to original sources
PubMed1979

Uptake and clearance of inhalation anesthetics in man.

The uptake, distribution, and clearance of inhaled vapors is governed by rules of partial pressure equilibration in a multicompartmental system. Since halogenated anesthetic agents are not soluble in water, biotransformation is their only clearance pathway during anesthesia. When apparent steady state is reached, the rate of overall metabolism can be determined from the pulmonary uptake rate. As a result of metabolism, pulmonary uptake increases but the concentration of inhaled vapor in blood and tissues decreases, and only a fraction of uptake is exhaled following anesthesia. Uptake and pulmonary clearance of five halogenated anesthetic agents were studied in 45 surgical patients. The susceptibility to biotransformation increases in the following order: isoflurane, enflurane, halothane, fluroxene, methoxyflurane.

Anesthesia, Inhalation↗
PubMed1978

Glutathione depletion following inhalation anesthesia.

Glutathione depletion following inhalation of halogenated anesthetics was investigated as a possible mechanism of toxic reactions associated with anesthesia. Concentrations of reduced glutathione were measured in the blood, liver, lung and kidney of the mouse after anesthesia with enflurane, fluroxene, halothane, isoflurane, methoxyflurane, or trichloroethylene. The anesthetic had no effect on glutathione concentrations in tissues except when fluroxene was used. After two hours of fluroxene anesthesia, glutathione in liver, lung, kidney, and blood was depleted by 93, 85, 85, and 61 per cent, respectively. The depletion was dose-dependent and was more extensive in animals anesthetized after phenobarbital pretreatment. Glutathione was also depleted in livers and lungs of rats anesthetized with fluroxene (60 and 38 per cent, respectively). In blood of rhesus monkeys anesthetized with fluroxene, glutathione was depleted by only 13 per cent. Extents of glutathione depletion are related to fluroxene toxicities in the three species studied.

Anesthesia, Inhalation↗
PubMed1977

Metabolism and toxicity of 2,2,2-trifluoroethyl vinyl ether.

A review on metabolism and toxicity of the fluorinated anesthetic agent, fluroxene, is presented. Fluroxene anesthesia is nontoxic to man but fatal to many experimental animals. The fluroxene molecule (2,2,2-trifluroethyl vinyl ether) is composed of two moieties; both are toxic as a result of their metabolism: the vinyl moiety destroys heme of cytochrome P-450 while being metabolized to the final product, CO2. The trifluoroethyl moiety is oxidized to trifluoroethanol (TFE) and trifluoroacetic acid (TFAA), and the acute toxicity of fluroxene is related to this pathway. The ratio of metabolities (TFAA to TFE) excreted by different species exposed to fluroxene varies; whenever highly toxic TFE is the major metabolite, fluroxene toxicity is high (rodents, dogs, phenobarbital pretreated monkeys), whenever TFAA is the major metabolite (man, monkey) fluroxene is not toxic. Toxicity in different species also correlates with the extent of glutathione depletion following fluroxene exposure. Fluroxene metabolism and toxicity are modified by drugs metabolized by or affecting the activity of the microsomal cytochrome P-450-system or enzymes involved in ethanol metabolism. The susceptibility of fluroxene to two enzymatic systems which are modified by environmental and genetic factors may explain the large differences in fluroxene toxicity to various species. The fate of one-third of fluroxene administered to man remains unknown.

Animals↗
PubMed1976

Metabolism of methoxyflurane in man.

Excretion of methoxyflurane was studied in 12 patients receiving anesthesia in a closed rebreathing circuit at a constant alveolar concentration of approximately 0.24 per cent. The mean methoxyflurane uptake was 18 g (range 7.6-31 g) during a mean time of anesthesia administration of 2 hours, 18 minutes (range 55-309 minutes). An average of 19 per cent of the uptake was recovered unchanged in the exhaled air after anesthesia. Urinary excretion of organic fluorine, fluoride, and oxalic acid was equivalent to 29, 7.7 and 7.1 per cent of methoxyflurane uptake, respectively. Approximately a third of the uptake remained unrecovered. It is postulated that a portion of the unrecovered drug became permanently bound to tissues and hence its excretion was delayed beyond the period of the study.

Acetates↗
PubMed1976

Fluoride in bone of rats anesthetized during gestation with enflurane or methoxyflurane.

Fluoride concentrations in maternal and fetal bones were measured following exposure of pregnant rats to methoxyflurane and enflurane anesthesia. Fluoride content in fetal bone increased significantly only after exposure to methoxyflurane, and then only when methoxyflurane was administered after 12 days of gestation, when ossification of fetal bone begins. Fluoride concentrations in maternal bone increased following both anesthetics, except in rats exposed to methoxyflurane after 15 days of gestation, when ossification of many fetal skeletal parts is in progress and fluoride is preferentially deposited in the fetal skeleton.

Anesthesia, Inhalation↗
PubMed1975

Fluroxene toxicity induced by phenobarbital.

Because of reports of fluroxene toxicity in man, the effect of phenobarbital treatment on the toxicity and metabolism of fluroxene was studied in 9 rhesus monkeys. Six monkeys that were exposed to a mean calculated alveolar fluroxene concentration of 5.8% for 4-hr periods up to a total of 16 hr showed no evidence of toxicity. Two animals were sacrificed after a single 4-hr exposure to obtain control measures of fluroxene metabolites in tissues. Four monkeys that had previously survived received exposures to fluroxene and 3 monkeys that had no exposure to fluroxene died during fluroxene anesthesia after treatment with phenobarbital (mean time, 3 hr). Toxicity was manifested by arterial hypotension, pulmonary edema, and arterial hypoxemia. Phenobarbital treatment enhanced production of fluroxene metabolites, including the highly toxic trifluoroethanol. Concentrations of trifluoroethanol in mixed-expired gas, blood, and urine, and of total nonvolatile fluorine in blood, urine, and tissues of animals treated with phenobarbital were 2 to 10 times as in control animals. The results suggest that the rhesus monkey is a valuable model for the study of fluroxene pharmacology and that inclusion of an enzyme-inducing challenge in the evaluation of potential toxicity of other anesthetics seems warranted.

Anesthesia↗
PubMed1975

Resistance of isoflurane to biotransformation in man.

Pulmonary and renal excretion of isoflurane and its metabolites was studied in nine surgical patients following administration of known quantitities of isoflurane. Uptake and pulmonary washout were predictable by a mathematical model for inert vapors. The agreement between predicted and experimental data supports the view that isoflurane is subject to little or no biotransformation. The average recovery in exhaled air was 95 per cent, SE 7 per cent. The postoperative increase of urinary excretion of fluoride and organic fluorine accounted for less than 0.2 per cent of fluorine administered as isoflurane. This small extent of biotransformation is probably biologically insignificant, but only after extensive clinical experience can the hazard of delayed toxic response be conclusively evaluated.

Adult↗
PubMedDate not supplied

Uptake and excretion of 1-bromo-1,2,2-Trifluorocyclobutane (42M-9) in man: comparative study on pharmacokinetics and metabolism of inhalation anesthetics.

1-bromo-1,2,2-trifluorocyclobutane (42M-9) has physical properties similar to those of methoxyflurane and has been suggested for use as an anesthetic agent. Its MAC value, predicted from its lipid solubility, is 0.26 percent. No clinically significant changes were observed in cardiovascular or respiratory function or in clinical laboratory tests. Ventricular dysrhythmias were not seen in this study at analgesic concentrations in contrast to those reported at anesthetic concentrations by others. Pulmonary uptake was high and wash-out was slow. The total amount exhaled comprised 60 percent of the dose. Fluorine, equivalent to 11 percent of total uptake, was rapidly excreted in urine as nonvolatile fluorinated metabolites. An additional 9 percent of 42M-9 was degraded to fluroide and excreted in urine. Since an amount of fluoride equivalent to that excreted in the urine tends to be deposited in the skeleton, approximately 29 percent of uptake may possibly be accounted for as metabolites. Based on fluorine recovery, the fate of 11 percent of 42M-9 uptake remains unknown. The kinetics of uptake, metabolism and excretion of 42M-9 did not differ significantly over a five-fold change of inspired concentration. A comparison of the pulmonary clearance of unaltered 42M-9 and the fraction of uptake converted to urinary metabolites or unrecovered with those of other volatile halogenated anesthetics and their physical properties supports the conclusion that 42M-9 is relatively resistant to biotransformation.

Anesthesia, Inhalation↗