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Biomedical subjects

M K Tham

Publications and source records attributed to M K Tham.

6 recordsLinked to original sources

Liquid ventilation of primates.

Three adult monkeys were anesthetized with ketamine and ventilated with fluorocarbon liquid [perfluoro bis (1, 4-isopropoxy) butane (Caroxin-D)] at 1 atmosphere on two separate occasions. During five runs, liquid ventilation was continued for 60 minutes. The sixth run was continued for ten minutes. Arterial blood gas levels during and after liquid ventilation were adequate for survival. Three years after the first period of liquid ventilation, the animals were killed. Approximately 0.001 mg of fluorocarbon per gram of tissue was present in the kidney, liver, brain, spleen, muscle, and heart. Fat contained approximately seven to nine times this amount, and the lung and pulmonary lymph nodes contained approximately 1,000 times this amount. In no case was it clinically evident that the monkeys had undergone periods of liquid ventilation. We conclude that primates can be ventilated successfully with liquid fluorocarbon on at least two separate occasions and can return to breathing air without obvious deleterious effects, but fluorocarbon is retained in small amounts for at least three years.

Adipose Tissue

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

Anesthetic solubility coefficients for maternal and fetal blood.

Solubility coefficients for seven inhalation anesthetic agnets were determined in maternal and fetal blood at 37 C. Halothane, isoflurane, diethyl ether, and nitrous oxide were significantly more soluble in maternal than in fetal blood, while methoxyflurane, fluroxene, and cyclopropane were significantly less soluble. Reasons for these differences cannot be accounted for by differences in the type or amount of hemoglobin present.

Anesthesia, Inhalation

Residual levels and biochemical changes after ventilation with perfluorinated liquid.

Twenty-three beagle dogs were ventilated with perfluorinated liquid, perfluoro-1-isopropoxy-hexane (Caroxin-F) for 1 h and were reconverted to gaseous breathing. Hematologic and biochemical changes were studied in five dogs for 1 yr and the remaining animals were followed for evidence of retained Caroxin-F for up to 3 yr. We found that the dogs could be ventilated with liquid Caroxin-F and returned to spontaneous breathing of gaseous oxygen with normal blood gas exchange within 24-72 h. Serum alkaline phosphatase, serum cholesterol, and white blood cell count increased with liquid ventilation but returned to normal in less than 1 wk. Trace amounts of Caroxin-F were detected by chromatography in all tissues studied for the entire 3-yr period. The highest levels of Caroxin-F were found in the lungs and associated lymph nodes. No histologic evidence of the presence of Caroxin-F was seen except for local accumulations of vacuolated macrophages in the lungs and associated lymph nodes. We conclude that Caroxin-F can be breathed without residual deleterious effects, even though trace amounts remained for at least 3 yr.

Alkaline Phosphatase

Increase in anesthetic uptake, excretion, and blood solubility in man after eating.

Blood-gas partition coefficients of N2O, enflurane, halothane, methoxyflurane, and isoflurane were measured on blood samples from 12 healthy male volunteers before and after eating. The solubility values determined while volunteers fasted substantiate previously reported blood-gas partition coefficients for enflurane, isoflurane, and halothane. Solubility values for methoxyflurane and N2O were slightly greater and smaller, respectively, than accepted values. The uptake and excretion of N2O, enflurane, halothane, and methoxyflurane also were measured in 6 of these subjects in the fasted and postprandial states. Subjects breathed a constant, inspired mixture containing trace concentrations of all 4 gases. Eating increased blood solubility by 17 to 24 percent for all agents except N2O. Accordingly, the rates of rise of the end-tidal enflurane, halothane, and methoxyflurane concentrations were 7 to 8 percent below control, and the rates of anesthetic uptake increased 20 to 23 percent. Simulation studies showed that the increased ventilation induced by eating opposed and, therfore, minimized the impact of increased blood solubility and cardiac output on the rate of end-tidal anesthetic rise. Changes in blood solubility did not correlate with levels of plasma triglycerides and cholesterol.

Adult