ACUTE AND CHRONIC PLEURAL CHANGES AFTER THE INTRAPLEURAL INSTILLATIONOF MITOXANTRONE IN RABBITS

A previous study demonstrated that the intrapleural injection of 2 mg/ kg mitoxantrone in rabbits resulted in a degree of pleurodesis which i s comparable to that seen after 35 mg/kg tetracycline but that the ani mals had a high mortality rate after this dose of mitoxantrone. The ob jective of the present study was to assess the acute pleural fluid fin dings, the acute gross and microscopic pleural findings, and the chron ic gross and microscopic findings in rabbits that received mitoxantron e. Mitoxantrone, 1.5 mg/kg, was instilled intrapleurally in 70 lightly anesthetized male rabbits. Groups of rabbits were sacrificed 1, 2, 4, 7, 15, 28, and 60 days after the injection. The intrapleural injectio n of mitoxantrone resulted in an exudative effusion on day 1. The pleu ral fluid contained predominantly neutrophils and had a mean lactate d ehydrogenase (LDH) level that exceeded 4,000 IU/liter. Over the follow ing week the volume of fluid diminished, the predominant cell became t he macrophage, and the LDH levels decreased to less than 400 IU/liter. Macroscopic examination of the pleural space revealed that the mean d egree of pleurodesis increased progressively over the 60-day observati on period. With microscopy, the mean degree of pleural fibrosis also i ncreased progressively. There were also substantial fibrosis and infla mmation of the underlying lung and the contralateral lung. The mortali ty rates were low in the first 28 days (3/70) but subsequently increas ed and exceeded 80% in the period between 60 and 120 days. This experi mental model of pleurodesis should be useful in future studies directe d toward uncovering the mechanisms of pleurodesis.