W. Oliver

Cardiopulmonary effects of short-term nitrogen dioxide exposure in conscious sheep

Abstract We used conscious sheep to (a) evaluate the airway effects of 2-hr exposures to 7.5 and 15 ppm NO2, and (b) to measure pulmonary hemodynamics after a 4-hr exposure to 15 ppm NO2. Bronchial reactivity to aerosolized carbachol (BR), tracheal mucous velocity (TMV), and mechanics of breathing were determined to assess whether NO2 induced airway effects immediately and 24 hr after exposure. The hemodynamic measurements included arterial blood gases, estimates of diffusing capacity, combined capillary blood and tissue volume, cardiac output, and pulmonary vascular pressures. In 10 sheep 7.5 ppm NO2 did not significantly alter mean pulmonary resistance prior to carbachol challenge (Rpul), BR, or TMV. However, in 5 of these 10 animals, enhanced BR was apparent immediately after the exposure. In 10 animals, 15 ppm NO2 did not produce significant changes in mean Rpul or BR, although in 7 animals there was a mean increase of 113% in Rpul immediately after the exposure, while BR was evident in 2 other sheep. TMV was, however, significantly depressed immediately after this exposure. In six sheep, who breathed 15 ppm NO2 for 4 hr, Rpul was significantly elevated immediately after the exposure. In the same animals, there were no changes in arterial blood gases, cardiac output, pulmonary vascular pressures, systemic pressure, diffusing capacity, and combined pulmonary tissue plus capillary blood volume. We conclude that in conscious sheep (a) exposures to 7.5 and 15 ppm NO2 for 2 hr may induce BR or elevations in Rpul, (b) exposure to 15 ppm NO2 for 2 hr depresses TMV, while exposure to 7.5 ppm NO2 for 2 hr has no effect on TMV, and (c) 15 ppm NO2 for 4 hr has no effects on pulmonary hemodynamics.

Changes in airway permeability and responsiveness after exposure to ozone

The purpose of this investigation was to examine the relationship between airway responsiveness and the permeability of histamine through the airways in conscious sheep after exposure to ozone (O3). Airway responsiveness was assessed by measuring the change from baseline in mean pulmonary flow resistance following a controlled 2-min inhalation challenge with 1% histamine, containing 200 microCi/ml of [3H]histamine. The rate of appearance of the [3H]histamine in the plasma during inhalation challenge was used to estimate airway permeability. To perturb the airways, conscious sheep were exposed to either 0.5 or 1.0 ppm O3 for 2 hr via an endotracheal tube. Airway responsiveness and airway permeability were measured prior to and 1 day after exposure. In six sheep exposed to 0.5 ppm O3, increased airway responsiveness and airway permeability were observed 1 day after exposure. Four of seven sheep exposed to 1.0 ppm O3 had enhanced airway responsiveness and airway permeability, while the remaining three sheep showed corresponding decreases in airway responsiveness and airway permeability. Since the O3-induced directional changes in airway responsiveness paralleled the directional changes in airway permeability in both the positive and negative directions, it was concluded that changes in airway responsiveness to inhaled histamine following exposure to O3 may be related to concomitant changes in airway permeability to this agent.

Effects of Nitric Acid on Carbachol Reactivity of the Airways in Normal and Allergic Sheep

The airway effect of a 4-hr exposure (via a Plexiglas hood) to 1.6 ppm nitric acid vapor were evaluated in seven normal and seven allergic sheep, i.e., animals that have a history of reacting with bronchospasm to inhalation challenge with Ascaris suum antigen. The nitric acid vapor was generated by ultrasonic nebulization of a 2% nitric acid solution. Airway effects were assessed by measuring the change in specific pulmonary flow resistance before and after a standard inhalation challenge with 2.5% carbachol aerosol. Nitric acid exposure did not produce bronchoconstriction in either group. Pre-exposure increases in specific pulmonary flow resistance after carbachol inhalation were 68% (SD +/- 13%) and 82% (SD +/- 35%) for the normal and allergic sheep, respectively. Within 24 hr, the largest post exposure increased in specific pulmonary flow resistance for the normal and allergic sheep were 108% [SD +/- 51% (P less than .06)] and 175% [SD +/- 87% (P less than .02)], respectively. We conclude that a short-term exposure to nitric acid vapor at levels below the industrial threshold limit (2 ppm), produces airway hyperreactivity to aerosolized carbachol in allergic sheep.

Impaired tracheal mucus transport in allergic bronchoconstriction: Effect of terbutaline pretreatment

The transport velocity of mucus within the trachea, pulmonary resistance, and arterial blood gas composition were measured in intubated conscious sheep with Ascaris suum sensitivity before and during allergic bronchoconstriction. Inhalation of A. suum extract for 15 min increased mean pulmonary resistance significantly from 1.9 cm H2O . L-1 sec-1 to 5.1 cm H2O . L-1 sec-1 after 60 min and to 4.5 cm H2O . L-1 sec-1 after 120 min, while it decreased mean arterial PO2 from 85 to 59 and 53 mm Hg, respectively, without altering arterial PCO2 or pH. This was associated with a decrease in mean mucus velocity from 11.2 to 6.0 and 5.7 mm min-1, respectively. The decrease in mucus velocity was accompanied by endoscopically visible increases in the quantity of tracheal mucus. No alterations in mucus velocity or pulmonary resistance were observed in animals who inhaled a control antigen (ragweed) or breathed a mixture of 10% oxygen 90% nitrogen, which produced a mean arterial PO2 of 51 mm Hg. The administration of 0.25 mg terbutaline sulfate by subcutaneous injection prior to A. suum challenge prevented the changes in mucus velocity, pulmonary resistance, and arterial PO2. We conclude that the decreased mucus velocity in the trachea during antigen-induced bronchoconstriction in conscious sheep is related to the allergic response, and can be prevented by the subcutaneous administration of terbutaline sulfate, a beta adrenergic agonists. This suggests that the protective effect of terbutaline sulfate in antigen-induced bronchoconstriction includes the effect on the associated impairment of mucociliary function.