Abstract
The present study was designed to systematize the patterns of cardio-pulmonary impairment caused by diffuse interstitial fibrosing pneumonitis. Forty mature rabbits were used. Thirty-five rabbits were repeatedly injected with 2mg/kg of body weight of N-methyl-N-nitrosourethane (MNU) for two weeks intravenously. After the administration of MNU several degrees of the interstitial fibrosing pneumonitis were obtained.
The changes in pulmonary ventilation, the impairment of alveolar gas exchange and the hemodynamic findings were investigated comparing with the morphologic findings of the lung.
Conclusions were as follows.
1) Morphologic findings in lungs; Two weeks after the initial injection of MNU the lung-weight of rabbits was increased and the alveolar walls were diffusely thickened by capillary congestion and intraseptal edema with some grades of neutrophilic cell infiltration.
From four weeks after the injection such acute infiltrations were less prominent and the weight of lungs was decreased, but the alveolar walls were slightly and unevenly thickened with some quantity of collagen fibers. After more than twelve weeks the fibrosing on the walls was highly advanced. In several places, alveolar spaces shrunk and were destroyed by the proliferation of the collagen fibers. The weight of lungs increased again but neither necrosis nor significant intraalveolar exudate was seen in any sections. These findings were divided into following three stages.
Stage 1: Acute infiltrative pneumonitis.
Stage 2: Minimal and/or moderately advanced fibrosing pneumonitis. (proliferating of fibrosis)
Stage 3: Far-advanced fibrosing pneumonitis with destroyed alveoli.
2) The values of the lung-compliance were decreased markedly in the stage of acute infiltrative pneumonitis and in the stage of far-advanced fibrosing pneumonitis.
3) The values of arterial PO2 decreased in relation with increasing the weight of lungs. During inspiration with pure oxygen for thirty minutes, the values of arterial PO2 in stage minimal or moderately advanced pneumonitis rose to the same level as in normal lungs. In the stages of acute infiltrative pneumonitis and far-advanced fibrosing pneumonitis, however, the values of arterial PO2 remained less than 350mmHg in spite of inhalation with pure oxygen. From aboves, the impairment of alveolar gas diffusion or the inequality of ventilation-perfusion ratio was suggested the cause of hypoxemia in the former. In the latter the increase in venous-to-arterial true shunt was the most important factor of hypoxemia.
4) In the majority of MNU-treated rabbits the right ventricular systolic pressure increased in relation with the decrease in the values of arterial PO2. The right ventricular walls were increased in weight, and myocardial fibers on the right side were also thickened with the continuation of higher systolic pressure.
