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Biomedical subjects

A Steward

Publications and source records attributed to A Steward.

34 records · Page 2Linked to original sources

Low level antigen responses in guinea-pig lung strip.

Guinea-pigs were sensitized either by i.p. administration or by a novel procedure involving inhalation of ovalbumin (2, 0.2 and 0.002%) on days 0, 5 and 19 respectively. Lung strips from these guinea-pigs were challenged with both low (0.02 micrograms/ml) and high (10 micrograms/ml) concentrations of ovalbumin and the responses compared. Whereas the low level antigen gave consistent contractions following aerosol sensitization, no response was observed from the i.p. sensitized guinea-pig lung strips. Marked differences were also observed following the high ovalbumin challenge, where the aerosol sensitized lungs gave almost twice the response as tissue from the i.p. sensitized guinea-pigs, the former being approximately 140% of that observed with acetyl-beta-methyl choline (1 mM). Furthermore, the response elicited in the lungs from aerosol sensitized guinea-pigs were not modified by the addition of high concentrations of the H1-antagonist diphenhydramine (100 microM), before or subsequent to challenge. The data suggest that the aerosol sensitization procedure gives rise to a contractile response in guinea-pig lung strips which contains no observable histamine component.

Anaphylaxis↗

A new in vivo method for the measurement of repetitive anaphylactic responses in the guinea-pig.

The established Konzett-Rossler bronchorespiratory model has been combined with a unique ovalbumin sensitization procedure to give a novel method to measure anaphylaxis in the anaesthetized guinea-pig. Following antigen challenge, up to eight equal bronchoconstrictor responses to the same dose can be generated from a single animal over a 120 min period. Total inhibition of the anaphylactic response can be elicited by four different classes of compound, namely salbutamol, mepyramine, theophylline and dimaprit. Cromoglycate failed to cause any inhibition. The method is discussed with particular reference to the antigen sensitization procedure, which differs substantially from other regimens previously employed and gives rise to heat labile antibody.

Albuterol↗

Absorption and disposition of [14C]-molsidomine in laboratory animals.

14C-Labelled N-ethoxycarbonyl-3-morpholinosyndnonomine(14C-molsidomine, Corvaton) was administered orally to mouse, rat, rabbit, dog and rhesus monkey, and i.v. to rat and dog, at a dose level of 6 mg/kg-1. The rates and routes of excretion of radioactivity were determined. The oral dose was well-absorbed in all species and most (greater than 75%) of the radioactive dose was excreted in urine. In rat and dog less than 1% of the dose was present as expired 14CO2. In dog and rhesus monkey, small amounts of radioactivity were eliminated relatively slowly. In rat, dog and rhesus monkey, the three species examined in detail, radioactivity was generally distributed throughout the body 4-10 days after dosing. Levels were highest in liver, pelt, blood and the gastrointestinal tract. Whole-body autoradiographic studies in rat and rhesus monkey showed that at 4 days post-dose, radioactivity was highest in stomach wall and was distributed into other tissues in lesser amounts. In view of its mode of action, it was interesting that radioactivity was also associated with the heart muscle and aorta walls.

Animals↗

Halothane solubility in human blood.

In a study of the influence of nutritional state on halothane anaesthesia, results were obtained which showed how the blood/gas partition coefficient for halothane varied with blood chemistry in 20 patients undergoing elective surgery. For each patient the partition coefficient lambda was measured by equilibration at 37 degrees C of a blood sample with a 1% halothane in 5% carbon dioxide in air mixture, followed by chemical extraction and estimation of the halothane content by gas chromatography. The haematocrit and haemoglobin, serum albumin, total protein, triglyceride and cholesterol concentrations were measured by routine laboratory methods. Regressions were sought of lambda on each of these, and on the globulin concentration and the ratios of albumin: globulin and albumin: total protein, deduced from these determinations. The only statistically significant regression (P = 0.0004) was that of lambda on the serum triglyceride concentration (T) (mmol/litre): lambda = 1.83 + 0.424T. The dependence of lambda on haemoglobin concentration was not statistically significant, but the slope of the regression was consistent with those of previous investigators. The regressions of lambda, corrected to the mean triglyceride concentration, on the ratios of albumin: globulin and albumin: total protein were not statistically significant but were not significantly different from an earlier reported result.

Anesthesia, Inhalation↗

Pharmacokinetics of halothane in the dog. Comparison of theory and measurement in individuals.

After surgical preparation under pentobarbitone anaesthesia seven dogs of mean body weight 31 kg were ventilated with 1% halothane for 80 min. At 1, 2, 5, 10, 20, 40 and 80 min after the start of the halothane administration blood samples were taken from the femoral artery and pulmonary artery and from a cerebral, a renal and a femoral vein. At 80 min a biopsy sample of skeletal muscle (psoas) was taken. The halothane tension in all samples was determined by extraction into carbon tetrachloride followed by gas chromatographic analysis using chloroform as an internal standard. The measured tensions were compared with tensions computed from a multi-compartment model of the uptake and distribution of halothane in the body. The model was quantified by measurements, in each individual, of total body mass, the masses of the major organs and the solubility of halothane in the major organs and tissues; by measurements of blood volume and solubility in blood at the start and finish of the halothane administration; and by repeated measurements of alveolar ventilation, cardiac output and body temperature. For the original version of the model, the computed tensions deviated from the measured tensions to an extent greater than could be attributed to experimental error and in a manner which could be attributed to metabolism of halothane and probably to direct diffusion of halothane from well-perfused organs and lean tissues into fat. Direct experimental evidence of diffusion into perirenal fat was obtained in supplementary experiments. With the quantitation of the model distorted to mimic the processes of metabolism and diffusion, measured arterial tensions could be predicted with a mean error of -0.2 mm Hg (SD 0.6 mm Hg). The mean measured arterial tension was 3.5 mm Hg.

Animals↗

The solubility of halothane in canine blood and tissues.

In vitro measurements were made of the solubility of halothane (about 1%, carried in 5% carbon dioxide in air) in tissues taken from dogs, mostly Alsatians, and usually after about 8 hr anaesthesia with pentobarbitone and halothane. The mean Ostwald solubility coefficient lambda in atm- minus 1 at 37 degrees C, for seven to 21 animals, were: brain 6.03, gut 4.23, cardiac muscle 4.88, kidney 4.95, liver 6.64, skeletal muscle (psoas) 5.45. For the gracilis muscle solubilities up to 20 atm- minus 1 were obtained. Solubility in blood was shown to increase significantly with haematocrit and haemoglobin and to be significantly higher in blood from unanaesthetized than from anaesthetized animals. The best-estimate equations were lambda-2.38 + 0.042H for the unanaesthetized condition and lambda-1.69+0.049 H for the anaesthetized condition, where H is haematocrit %. Combining the present results with those for other species showed that the solubility of halothane increased fairly systematically from blood to kidney to brain to liver, and from ox to man to dog to rabbit.

Anesthesia↗

Organ weights in the dog.

The masses of the major organs in eight large dogs, mostly of alsatian type, which had been subjected to about 8 h anaesthesia and surgery, were determined by post mortem weighing. The organ masses as percentage of the total body mass (29.6 +/- 6.0 kg, mean +/- sd) were: brain 0.28 +/- 0.05, gut 2.61 +/- 0.49, heart 0.73 +/- 0.04, kidneys 0.40 +/- 0.07, liver 2.36 +/- 0.38.

Animals↗