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Biomedical subjects

G A Chapman

Publications and source records attributed to G A Chapman.

At least 37 records · Page 2Linked to original sources

Toxicity of fenvalerate to developing steelhead trout following continuous or intermittent exposure.

Environmental toxicant exposure commonly vary in terms of duration and concentration. However, laboratory toxicity tests usually entail continuous exposures to constant concentrations. We compared survival, growth, and toxicant accumulation in early life-stage steelhead trout intermittently or continuously exposed to fenvalerate (FV) for 70 d after fertilization. Acute lethality was assessed in ancillary 96-h LC50 determinations with juvenile fish. Intermittent exposures were daily 4.5-h introductions of toxicant, and continuous exposures were to constant concentrations. All tests were conducted in a flow-through dilution apparatus, and mean concentrations for the entire exposure period were calculated for comparisons between regimens. The respective 96-h LC50 values for intermittently and continuously exposed were 88 and 172 ng/l. In the subchronic study, marked lethality (32%) and reduced terminal weight (50%) were found following exposures to cyclic FV concentrations that yielded an average of 80 ng/l (peak of 461). Continuous exposure to 80 ng FV/l did not affect these parameters. At mean FV concentrations above 20 ng/l, bioaccumulation was greater following intermittent than continuous exposure. Interaction of partitioning and elimination processes may partially explain differences in FV accumulation and subsequent toxicity.

Animals↗

Effects of leukotriene D4 on mucociliary and respiratory function in allergic and nonallergic sheep.

We determined the effect of aerosol challenge with leukotriene D4 (LTD4) on specific lung resistance (sRL) and tracheal mucous velocity (TMV) in conscious sheep with (allergic) and without (nonallergic) Ascaris suum hypersensitivity. In allergic sheep LTD4 in concentrations of 50, 100, and 150 micrograms/ml produced dose-dependent increases in mean sRL by 44 (P = NS), 154 (P less than 0.05), and 233% (P less than 0.05), respectively. The increase in sRL produced by 150 micrograms/ml LTD4 was prevented by FPL 55712, an antagonist of slow-reacting substance of anaphylaxis. In nonallergic sheep 150 micrograms/ml LTD4 failed to elicit a significant change in sRL. In contrast to the changes in airway mechanics, concentrations of LTD4 as low as 25 micrograms/ml produced significant decreases in TMV in allergic sheep. The maximum decrease in TMV at this dose occurred 2 h after challenge; with larger doses of LTD4 (100 and 150 micrograms/ml) the maximum effect was observed 3 h after challenge. Furthermore, 150 micrograms/ml LTD4 reduced TMV in nonallergic sheep (mean decrease 43%, P less than 0.05). FPL 55712 only had a minor effect on the LTD4-induced decreases in TMV. We conclude that allergic sheep exhibit greater airway responsiveness to inhaled LTD4 than nonallergic sheep but that this difference is not evident for the concomitant changes in mucociliary transport. This suggests that the allergic state is associated with an increased responsiveness to LTD4 in tissues controlling airway caliber but not in those contributing to mucociliary function.

Aerosols↗

Influence of two-phase gas-liquid interaction on aerosol deposition in airways.

Many patients with chronic simple bronchitis, viz., chronic productive cough without major airway obstruction, frequently show enhanced aerosol deposition in the airways. We hypothesized that this phenomenon might relate in part to wave motion of an accumulated layer of mucus caused by dynamic, two-phase gas-liquid interactions. In the present investigation, two-phase gas-liquid interaction was demonstrated in vivo by observing wave motion during tidal breathing of radiopaque-labeled viscous and viscoelastic fluids that had been added to distal tracheas of conscious sheep. Total aerosol deposition in the lung and mean pulmonary resistance (RL) were measured after addition of 4 to 10 ml of viscoelastic or viscous fluids to the distal main bronchi of conscious sheep. Change in aerosol deposition over baseline after fluid addition was compared with change in RL. In 21 experiments, 5 for each of 3 viscoelastic fluids with varying characteristics and 6 for a viscous fluid, aerosol deposition was significantly enhanced in every experiment, irrespective of the type of fluid added. This increase in aerosol deposition ranged from 13 to 66% above baseline. The RL increased in 5 of the 6 experiments with viscous fluid and in 4 of the 15 experiments with viscoelastic fluids. There was less wavelike motion with viscous than with viscoelastic fluids. These results suggest that two-phase gas-liquid interaction in the airways can account for increased aerosol deposition with little alteration in airway resistance.

Aerosols↗

Differences between inhaled and intravenous carbachol in detecting O3-induced airway effects.

The response of specific lung resistance (SRL) to inhalation of 5 and 10 mg/ml carbachol was compared with the response of SRL to intravenous infusion of 2 and 5 micrograms/kg carbachol before and after a 2-day exposure to 0.5 ppm ozone (O3) in eight conscious sheep. Airway reactivity was defined as the slope of the dose-response curve and airway sensitivity as the largest increase in SRL after carbachol challenge. O3 exposure did not alter mean airway reactivity or mean airway sensitivity as determined by inhalation challenge. In contrast, O3 exposure significantly increased mean airway reactivity by 34% (P less than 0.01) and mean airway sensitivity by 31% (P less than 0.01) as assessed by intravenous challenge. The failure of O3 exposure to enhance responsiveness to inhaled carbachol may have been related to decreased airway penetration of the aerosol, possibly due to mucus hypersecretion. However, O3 exposure may have had a direct effect on the airway smooth muscle, thereby explaining the increased response to infused carbachol.

Aerosols↗

Duration of mucociliary dysfunction following antigen challenge.

Antigen-induced bronchospasm is associated with an impairment of airway mucociliary clearance, but the duration of this defect has not been examined. In the present study, we determined the time course of mucociliary dysfunction following inhalation challenge with Ascaris suum extract in conscious sheep with hypersensitivity to this antigen. Tracheal mucous velocity (TMV) as an index of mucociliary function, pulmonary resistance (RL), and arterial oxygen tension (Pao2) were measured prior to, immediately after, and serially for 8 h after inhalation challenge. TMV and Pao2 were then measured periodically for at least 2 wk. Immediately after A. suum challenge, mean RL increased to 264% of base line (P less than 0.05), and mean Pao2 decreased to 61% of base line (P less than 0.05). By 2 h postchallenge, mean RL and Pao2 had returned to base line but mean TMV had fallen to 61% of base line (P less than 0.05). Mean TMV reached a minimum of 35% of base line after 5 h (P less than 0.05) and remained significantly depressed between 37% and 54% of base line for 7 days; by day 9, mean TMV had returned to base line. Inhalation challenge with a control antigen (ragweed) failed to alter mean TMV, RL, and Pao2 during the first 8 h and TMV and Pao2 at any time throughout the 2-wk observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of brief and intermediate exposures to sulfate submicron aerosols and sulfate injections and cardiopulmonary function of dogs and tracheal mucous velocity of sheep.

Pulmonary mechanics of anesthetized dogs were not changed or were minimally altered by breathing the following compounds as submicron aerosols in concentrations up to 17.3 mg/m3 for 7.5 min: (1) sodium chloride (as a control), (2) sodium sulfate, (3) ammonium sulfate, (4) zinc sulfate, (5) zinc ammonium sulfate, (6) ammonium bisulfate, (7) aluminum sulfate, (8) manganese sulfate, (9) nickel sulfate, (10) copper sulfate, (11) ferrous sulfate, and (12) ferric sulfate. Submicron aerosols of these compounds in concentrations of 4.1-8.8 mg/m3, administered for 4 h to anesthetized dogs, did not affect mechanics of breathing, hemodynamics, and arterial blood gases. In conscious sheep, tracheal mucous velocity was not altered by exposure to the submicron aerosols of the sulfate compounds. None of these compounds, injected iv in a dose of 1 mg, had adverse effects on mechanics of breathing, pulmonary and systemic hemodynamics, or arterial blood gases. In 100-mg injections, zinc sulfate and zinc ammonium sulfate produced a fall in cardiac output, systemic hypotension, hypoxemia, and metabolic acidosis. Copper sulfate at this dose produced pulmonary hypertension, a fall in cardiac output, hypoxemia, respiratory acidosis, and a decrease of specific total respiratory conductance. It is concluded that submicron aerosols of sulfate salts do not have adverse cardiopulmonary effects when administered in high concentrations for up to 4 h. However, prolonged exposure to high concentrations of zinc sulfate, zinc ammonium sulfate, and copper sulfate aerosols should be carefully monitored because of the possibility that lower levels of these compounds in the bloodstream for long time period might have adverse cardiopulmonary effects.

Aerosols↗

Sulfur dioxide induced airway hyperreactivity in allergic sheep.

The effects of a four-hour exposure (via a Plexiglas hood) to sulfur dioxide (SO2) on airway reactivity was studied in both normal and allergic conscious sheep. Allergic sheep were defined as animals in whom inhalation of Ascaris suum extract resulted in an increase in mean pulmonary flow resistance (RL). Airway reactivity (delta RL) was assessed by measuring the increase in RL after 18 breaths of 0.25% carbachol, from an initial value obtained after 18 breaths of buffered saline. RL and delta RL were determined prior to, immediately after and 24 hours following SO2 exposure in three groups of sheep: six normal sheep exposed to 5 ppm SO2 (group A); six normal sheep exposed to 10 ppm SO2 (group B) and seven allergic sheep exposed to 5 ppm SO2 (group C). RL was not affected by SO2 exposure in any group but both groups B and C showed increases in delta RL 24 hours after exposure. Since the increase in delta RL was greater in group C than in either groups A or B, we conclude that allergic sheep have enhanced susceptibility to the injurious airway effects of SO2.

Airway Resistance↗

Effect of local radioactivity on trachael mucous velocity of sheep.

The effects of local isotope radiation and x-ray radiation on mucociliary transport of sheep were investigated. X-ray radiation from fluoroscopy equivalent to that used to determine tracheal mucous velocity in intact animals (approximately 3 min) did not alter transport of teflon discs in an isolated sheep trachael preparation. In conscious sheep, 2 ml of a solution containing 8 mCi of macroaggregates of albumin labeled with technetium-99m (99mTc) and 99mTc-pyrophosphate were instilled under direct vision into the trachea via a fiberoptic bronchoscope, providing an actual deposition on the tracheal epithelium of 1.8 to 2 mCi. Physiologic saline and unlabeled macroaggregates of albumin were instilled as control solutions. Tracheal mucous velocity measured by movement of teflon discs increased by 93.2 per cent with 99mTc-labeled macroaggregated albumin and 86.7 per cent with 99mTc-pyrophosphate (P less than 0.01), but no significant increase occurred after saline or unlabeled macroaggregates of albumin. Discrepancies in the values of trachael mucous velocity determined using inert particles and radioactive tracer solution or aerosols might be related in part to the local effects of the tracer radiation.

Animals↗

A new roentgenographic method for estimating mucous velocity in airways.

A new roentgenographic method is described for the estimation of mucous velocity in airways. Radiopaque discs of teflon mixed with bismuth trioxide were deposited in the trachea, and their motion was observed by a fluoroscopic image intensifier. Simultaneous measurements of disc movement were obtained by a previously reported cinebronchofiberscopic method and by the roentgenographic method in 6 anesthetized dogs. Mean +/- SD tracheal mucous velocity was 8.5 +/- 7.3 mm per min by the roentgenographic method, and 7.6 +/- 7.1 mm per min by the cinebronchofiberscopic method. Discrepancies between the 2 methods for individual disc velocities could be accounted for by the cumulative errors of both methods. The roentgenographic method was also used in 7 normal volunteers who did not have topical anesthesia of the tracheobronchial tree. The discs were blown through the inner channel of a bronchofiberscope, the tip of which was located just above the vocal cords. Placement of the discs on the tracheal mucosa generally did not produce coughing. Tracheal mucous velocity ranged from 7.4 to 19.4 mm per min as estimated from videotape recordings of the image intensifier images. There was no consistent difference in velocity between the erect or supine position, or after topical anesthesia with lidocaine.

Adult↗