Pulmonary vascular structural and functional changes in papain-induced emphysema in dogs

We evaluated the pulmonary circulatory effects of emphysema produced by papain in 6 dogs that received 4 weekly treatments of papain administered by aerosolization. A control group of 6 dogs received saline treatments. Hemodynamic measurements were performed during normoxic and hypoxic (10% oxygen) ventilation approximately 3 and 6 months after treatment. Baseline hemodynamic parameters were comparable in both groups and were unchanged at 6 months in the control group. In the papain-treated group at 6 months, there were significant reductions in PaO2 (95 +/- 4 to 79 +/- 3 mm Hg, p less than 0.005) and increases in mean pulmonary artery pressure (12 +/- 1 to 18 +/- 3 mm Hg, p less than 0.05) and pulmonary vascular resistance (2.0 +/- 0.3 to 6.2 +/- 2.1 units, p less than 0.01). Morphometric evaluation demonstrated increased medial thickness in muscular pulmonary arteries less than 50 mu in size. Morphologic evaluation confirmed the presence of panlobular emphysema with papain administration. We conclude that chronic emphysema produced in dogs by aerosol administration of papain results in elevated pulmonary artery pressure, which is characterized pathologically by medial hypertrophy of small pulmonary arteries. This model appears suitable for further study of the pathogenesis of pulmonary vascular disease associated with chronic lung disease.