Functional and morphologic changes caused by acute ozone exposure in the isolated and perfused rat lung

Ozone has been shown to increase airway resistance and/or airway reactivity in vivo in animals and humans. Because of the complexities inherent in studying this phenomenon in whole animals, we developed a model of ozone-induced effects on airway physiology using the isolated perfused rat lung. Rat lungs were suspended in an airtight chamber and perfused via the pulmonary circulation with a modified Krebs-Henseleit buffer containing 4.5% bovine albumin. Ventilation of the lungs was achieved by generating a fluctuating negative pressure within the chamber (-2 to -7 cm H₂O) at a rate of 60 breaths/min. The lungs were ventilated with humidified 95% air and 5% CO₂ alone (control condition) or mixed with ozone at 1.0 or 2.0 ppm. Transpulmonary pressure, flow rate, and tidal volume were recorded at 0, 1, 2, and 3 hours, and pulmonary resistance (RL) and dynamic compliance (Cdyn) were calculated. There was no significant difference in lung weight/total body weight ratios between the three groups at the end of the 3-h period. RL increased and Cdyn decreased in a time- and dose-dependent manner with ozone exposure. The percent increase above baseline in RL ± SEM at 3 h was 9.4 ± 4.1% for control lungs, 21.0 ± 3.2% for 1.0 ppm ozone-exposed lungs, and 63.6 ± 13.5% for 2.0 ppm ozone-exposed lungs. The percent decrease below baseline in Cdyn ± SEM at 3 h was 27.4 ± 2.1% for control lungs, 37.1 ± 2.7% for 1.0 ppm ozone-exposed lungs, and 55.2 ± 7.3% for 2.0 ppm ozone- exposed lungs. Microscopically, there was moderate necrosis and sloughing of epithelial cells lining the airways of the ozone-exposed lungs, especially in the larger bronchioles and bronchi. These lesions were not seen in control lungs. We conclude that ozone-induced changes in pulmonary mechanics of this isolated rat lung model mimic those seen in whole animals, and that these changes occur independently of central neurogenic influences or circulating blood components.