In vivo and in vitro lung reactivity in elastase-induced emphysema in hamsters

Although patients with chronic obstructive lung disease often show airway hyperresponsiveness to constrictor challenge, the mechanisms underlying this hyperreactivity are unknown. In this study, we tested whether the elastase-induced hamster model of emphysema and bronchial secretory cell metaplasia shows a similar hyperreactivity. Four weeks after intratracheal administration of 0.2 mg/100 g body weight porcine pancreatic elastase, the animals were anesthetized and ventilated with a constant tidal volume of 5 ml/kg. Changes in airway pressure (Paw) were monitored before and after intravenous challenge with 0.7 mg/kg acetylcholine (ACh). There was a significant decrease in baseline Paw from 5.7 +/- 0.6 cm H2O in control animals (n = 6) to 4.0 +/- 0.6 cm H2O in emphysematous animals (n = 6). The peak Paw response to the intravenous challenge, normalized to the baseline Paw, was 2.9 +/- 0.4 in control animals, but it was significantly increased in the emphysematous animals to 4.4 +/- 1.1. Trachea, bronchi, and parenchyma from these lungs were challenged with cumulative dose of ACh and KCl. Sensitivity of the trachea and bronchi to ACh challenge, assessed as the log ED50, did not show differences between the two groups. However, the emphysematous parenchyma showed greater sensitivity to ACh compared with the control parenchyma. Trachea and bronchi from emphysematous animals showed significantly decreased maximal contractility to challenge with both ACh and KCl. In contrast, the emphysematous parenchyma showed significantly greater maximal contractility. These findings were independent of the baseline passive tension. This increased responsiveness may relate to increased passive distensibility of the emphysematous parenchyma.