Responses in Awake Guinea Pigs to Acid Aerosols

Abstract

This study reports experiments designed to evaluate the dose and temporal effects of an atmospheric pollutant, sulfuric acid (H2SO4) aerosol, on the dynamic components of the respiratory cycle. Ventilation was measured in a whole-body barometric plethysmograph in unanesthetized, unrestrained animals following a 4-h exposure to H2SO4 aerosol at 14.1, 20.1, or 43.3 mg/m3. Lung injury was assessed by histopathology and bronchoalveolar lavage (BAL). Aerosol exposure with H2SO4 caused marked alterations in both the magnitude and composition of the ventilatory response, which were both dose and time dependent. At the highest concentration tested, there was a significant increase in tidal volume (deltaVt) and a decrease in breathing frequency (f) immediately after exposure. Analysis of BAL fluid at this time showed increased inflammatory cells and protein in the acid exposed animals, and histology showed hyaline membranes and acute inflammatory cells in the proximal acinar region. By 24 h postexposure, f significantly increased whereas deltaVt decreased. This pattern of breathing was interspersed with short periods of apnea. The onset of rapid, shallow breathing was associated with histological evidence of diffuse pulmonary edema. By contrast, the immediate postexposure period at the lowest concentration of H2SO4 aerosol was characterized by a significant increase in f and little or no effect on deltaVt. These effects diminished with time, and at 24 h postexposure ventilatory parameters were indistinguishable from baseline values. An apparent crossover between the effects associated with the high and low exposure concentrations was seen at the intermediate exposure concentration; however, closer inspection of these findings on an animal-by-animal basis revealed two populations of animals with respiratory characteristics of either the high-exposure or low-exposure groups. The data suggest that the guinea pig exhibits complex interactions between dose and time to response that are consistent with the activation of neural reflexes. The indirect plethysmographic method provides a simple means to assess these responses in a model system that avoids the use of anesthetics, surgery, and restraint.

Neurokinin–1 Receptor Antagonist Inhibits Short–Term Sulfuric–Acid–Induced Airway Hyperresponsiveness in Sensitized Guinea Pigs

“…Tachykinins have been shown to have an important role in AHR and bronchoconstriction [6, 7, 8, 9, 10, 11, 12]. In exposure experiments with guinea pigs, it was reported that the selective tachyinin neurokinin–2 (NK 2 ) antagonist but not the selective neurokinin–1 (NK 1 ) antagonist inhibited SO 2 –induced bronchoconstriction [8], and that NK 2 antagonists inhibited citric–acid–induced AHR whereas NK 1 antagonists did not [10].…”