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Biomedical subjects

J A Graham

Publications and source records attributed to J A Graham.

117 records · Page 7Linked to original sources
PubMed1968

The effect of adrenaline on the tension developed in contractures and twitches of the ventricle of the frog.

1. The effect of adrenaline on contracture and twitch tension in frog's ventricle has been examined, using the superfused preparation.2. In 1 mM-Ca Ringer, contractures induced with excess KCl concentrations from 50 to 200 mM, are reduced by 1 x 10(-6) g/ml. adrenaline to an average of 0.62 of control values, in marked contrast to the well known positive inotropic effect of adrenaline on the heart twitch. This effect of adrenaline is directly dose dependent. Increasing [Ca](o) diminishes the effect of adrenaline on contracture tension, and on the twitch tension.3. Adrenaline has a significantly greater effect on the KCl contracture tension than noradrenaline or isoprenaline.4. In 1 mM-Ca Ringer, Na-free contractures are reduced to 0.72 of controls by 1 x 10(-6) g/ml. adrenaline. Adrenaline also significantly reduces tension in contractures induced by 50 c/s alternating current.5. The action of adrenaline on contracture tension is largely complete in 1-2 min at various rates of stimulation and calcium concentrations. A similar time course has been found for the effect of adrenaline on membrane potential.6. Pronethalol blocks the action of adrenaline on both twitch and contracture. The action on the contracture can also be blocked by ouabain (1 x 10(-5)M), and exposure of the tissue to K-free or Na-free Ringer solution.7. Adrenaline hyperpolarizes the membrane potential with a range of [K](o) from 0 to 200 mM. This effect is blocked by pronethalol and ouabain. After exposure to ouabain, adrenaline causes a significant decrease in the membrane potential. This may be due to an increase in the sodium permeability.8. At low values of the [Ca]/[Na](2) ratio, adrenaline takes a relatively constant number of beats for full action, but at high values of the ratio the development of full effect is largely time dependent.9. The time course of the effect on the twitch of changing from 0.5 to 2 mM-Ca Ringer has been studied at various rates of stimulation. The equilibration time has been found to depend on the heart rate.10. The effect on the contracture suggests that adrenaline decreases the calcium permeability. It is further suggested that the development of twitch tension is not due to direct Ca entry but is due to the release of Ca from a local store within or between the cells. The inotropic action of adrenaline is explained in terms of this store.

Animals↗
PubMedDate not supplied

The effects of intratracheally administered coarse mode particles on respiratory tract infection in mice.

Because coarse mode particles are rarely studied in their existing size ranges (greatest mass about 5-7 microns, aerodynamic diameter), we investigated the effects of four such particles, quartz, ferric oxide, calcium carbonate, and sodium feldspar, on host defenses against bacterial pulmonary infection. Mice which received intratracheal instillations of 10, 33, and 100 micrograms/mouse were exposed within an hour to aerosols of viable Streptococcus, and pneumonia-induced mortality was measured. At 33 and 100 micrograms/mouse, all particles significantly increased mortality. At the lower dose, only Fe2O3 caused a significant increase in mortality. To evaluate potential delayed effects, mice were challenged with the bacteria 24 h after exposure to 100 micrograms particles/mouse. Delaying the challenge did not significantly alter the response, except for the sodium feldspar group for which a partial recovery was observed. When mice exposed to 100 micrograms particles/mouse received aerosols of Klebsiella pneumoniae 24 h later, there was no significant effect on pulmonary bactericidal activity. For the model system used, it appears that Fe2O3, CaCO3, and sodium feldspar have effects roughly equivalent to quartz.

Aerosols↗
PubMedDate not supplied

Influence of ozone on pentobarbital pharmacokinetics in mice.

Previous studies have indicated that acute exposure to ambient concentrations of ozone (O3) as low as 196 micrograms/m3 (0.1 ppm) increases pentobarbital (PEN)-induced sleeping time in female mice. To elucidate potential mechanisms involved, additional studies were performed. A 3 h exposure to 9800 micrograms O3/m3 (5 ppm) did not affect brain concentrations of PEN at time of awakening, even though sleeping time was increased. Exposure for 3 h to 9800 micrograms O3/m3 (5 ppm) did not alter the pattern of brain or plasma metabolites of PEN. Pentobarbital clearance followed first-order kinetics with a one-compartment model. Mice exposed to 9800 micrograms O3/m3 (5 ppm) for 3 h had a 106% increase in the plasma half-life of pentobarbital; at 1960 micrograms O3/m3 (1 ppm) for 3 h, a 71% increase was observed. It therefore appears possible that PEN-induced sleeping time might be increased due to an decrease in hepatic metabolism of PEN.

Animals↗
PubMedDate not supplied

Influence of ozone and nitrogen dioxide on hepatic microsomal enzymes in mice.

Since ambient concentrations of ozone and nitrogen dioxide increase drug-induced sleeping time in female mice, potential mechanisms were sought by investigating the effects of these gases on hepatic microsomal mixed-function oxidases in female CD-1 mice. A 3-h exposure to 9800 microgram O3/m3 (5 ppm) or 9400 microgram NO2/m3 (5 ppm) did not change the concentration of cytochrome P-450 significantly. Aniline hydroxylase, but not aminopyrine N-demethylase or p-nitroanisole O-demethylase, activities were increased following a 3-h exposure to 9400 microgram O3/m3 (5 ppm). Aniline hydroxylase activity was also increased after a 2-d (5 h/d) exposure to 1960 microgram O3/m3 (1 ppm). None of these enzyme activities were affected by a 3-h exposure to 9400 microgram NO2/m3 (5 ppm). In these studies, O3 sometimes increased wet liver weight, and thus additional experiments were conducted. A 5-h exposure to 1960 microgram O3/m3 (1 ppm) caused a lesser decrease in body weight than the decrease observed after a similar air exposure. Liver wet weights were elevated after O3 exposure. However, there were no significant changes in liver dry weight, liver dry-to-wet-weight ratio, or ratios of liver (wet or dry) weight to body weight. From these data, it is concluded that mechanisms other than those investigated are responsible for the effect of O3 and NO2 on drug-induced sleeping time. However, the activity of one mixed-function oxidase was slightly increased by O3, indicating a hitherto unrecognized systemic effect of O3 exposure.

Animals↗
PubMedDate not supplied

Comparison of pulmonary biochemical effects of low-level ozone exposure on mice and rats.

The biochemical effects of a 5-d continuous exposure to 0.45 ppm (882 microgram/m3) O3, were studied in the lungs of 2-mo-old male, specific-pathogen-free mice (Swiss Webster) and three strains of rats (Long-Evans, Wistar, and Sprague-Dawley). The results, expressed per lung, indicated a general increase in lung weight, DNA and protein contents, oxygen consumption, sulfhydryl metabolism, and the activities of several NADP+-reducing enzymes for all exposed animals relative to their controls. When the increases in the two species (mice versus three strains of rats) were compared, the mice showed significantly higher increases than the rats in several parameters. The responses among the three strains of rats were variable, but the differences were not significant. These observations suggest that Swiss Webster mice may offer a more sensitive animal model than rats for studying the pulmonary effects of a given low-level O3 exposure.

Animals↗