Bleomycin is the antineoplastic agent used most commonly for the treatment of malignant pleural effusion. It is absorbed rapidly from the pleural space and does not elicit pleurodesis in the normal rabbit pleura. Mitoxantrone is a new antineoplastic that differs from bleomycin in that it binds to membranes. Accordingly it might remain in the pleural space for a longer period and produce a pleurodesis. The objective of this project was to determine whether mitoxantrone is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anesthetized male rabbits: 35 mg/kg tetracycline or 0.5, 1.0, or 2.0 mg/kg mitoxantrone. The animals were killed at 28 days and the pleural spaces assessed grossly for pleurodesis and microscopically for fibrosis and inflammation. The mean degree of gross pleurodesis did not differ significantly in the rabbits that received tetracycline (3.8 +/- 0.4) and in the rabbits that received 2 mg/kg mitoxantrone (3.2 +/- 1.3). The degree of pleural and lung inflammation was significantly greater after mitoxantrone than after tetracycline, both ipsilaterally and contralaterally. The mortality after the highest dose of mitoxantrone was 50%. From this study we conclude that the intrapleural administration of mitoxantrone in rabbits can produce a pleurodesis. The histologic picture after mitoxantrone administration differs markedly from that after tetracycline injection. After mitoxantrone injection there are many more inflammatory cells present on the side that received the injection, and there is much more fibrosis and inflammation in the contralateral pleura and lung. The model of pleural fibrosis following intrapleural mitoxantrone may be useful for the study of pleural fibrosis.

The mechanisms leading to a pleurodesis after the intrapleural injection of a sclerosing agent are not completely understood. The purpose of the present study was to make serial observations over 28 days on the pleural fluid findings and the gross and microscopic changes in the pleura after talc slurry administered intrapleurally at a high dose. Sixty-six rabbits received 400 mg/kg talc slurry. Ten to 12 rabbits were sacrificed 1, 2, 4, 7, 14, and 28 days after the intrapleural injection. At sacrifice the pleural fluid was measured and analyzed, and the pleural surfaces were studied grossly and microscopically. The intrapleural injection of 400 mg/kg talc slurry resulted in an acute exudative pleural effusion that persisted for 4 days. There was a progressive increase in the gross and microscopic fibrosis over the 28 days. Talc was present at the time of sacrifice in all animals. At 28 days there was a clinically significant pleurodesis in all rabbits; pleurodesis was not observed before this time. From this study we conclude that the intrapleural injection of 400 mg/kg talc slurry leads to an acute exudative pleural effusion and clinically significant pleurodesis that is present on day 28 but not day 14. It appears that the production of a pleurodesis requires higher doses of talc in rabbits without a chest tube than in humans with a chest tube.