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Study Objective: At the present time, talc administered either as a slurry or an aerosol is a popular agent for producing pleurodesis. Some investigators use iodized talc while others use plain talc. The purpose of the present study was to determine if iodized talc slurry produced a better pleurodesis in animals than did plain talc., Design: New Zealand white male rabbits were randomly assigned to receive talc slurry, 200 mg/kg, with or without the addition of 50 mg iodide intrapleurally. Approximately 10 rabbits in each group were killed 1, 2, 4, 7, 14, and 28 days after the injection. The amount and character of pleural fluid, the degree of pleural adhesions, and the microscopic changes were compared in the two different groups., Results: The pleural fluid findings, the gross adhesion score for the pleura, and the microscopic changes in the visceral pleura were essentially identical for the rabbits that received iodized talc and those that received plain talc. The injection of both plain talc and iodized talc produced a normoglycemic exudative pleural effusion that had, for the most part, disappeared by the fourth day postinjection. The amount of pleural fluid at 48 h was 3.3+/-0.6 mL in the plain talc and 2.2+/-0.5 mL in the iodized talc group. At 28 days, the mean degree of gross pleurodesis in the talc group was 2.6+/-0.2 compared with 2.3+/-0.2 in the iodized group, while the mean degree of microscopic fibrosis was 1.4+/-0.3 in the plain talc group compared with 2.0+/-0.3 in the iodized talc group., Conclusion: From this study, we conclude that the addition of 50 mg of iodide does not improve the results with talc slurry pleurodesis in rabbits.

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.

Tetracycline has been one of the most commonly used agents for producing a pleurodesis. However, it is no longer available due to more stringent requirements on the manufacturing process. The objective of this project was to determine whether Corynebacterium parvum is an effective sclerosant in an experimental model in rabbits. The following medications were instilled intrapleurally in anaesthetized male rabbits: tetracycline 35 mg.kg-1 or C. parvum 4 or 8 mg, all diluted with bacteriostatic saline solution. Twenty eight days after the instillation, the animals were sacrificed and the pleural spaces assessed macroscopically for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of C. parvum was ineffective in creating pleural fibrosis. The mean degree of pleurodesis in the 10 rabbits who received tetracycline was 3.5 +/- 0.7 (scale 0-4) whilst in the 10 rabbits that received 4 mg C. parvum it was 0.0 +/- 0.0, and in the 10 rabbits that received 8 mg C. parvum it was 0.5 +/- 0.8. Based on this study, we recommend that C. parvum should not be used as a pleural sclerosant in patients with normal pleura.

Insufflated talc is probably the most effective agent for creating a pleurodesis both in the clinical situation and in animals. However, the insufflation of talc requires an invasive procedure such as thoracoscopy or thoracotomy. Recently, there have been reports that talc in a slurry was effective in the clinical situation. The objective of this project was to determine whether talc in a slurry at varying doses is an effective sclerosant in an experimental model in rabbits. Talc, 50, 100, 200, and 400 mg/kg, in a 2-mL slurry was injected intrapleurally through a small catheter in male rabbits. Eleven rabbits received each dose. Twenty-eight days after the instillation, the animals were killed. The pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The degree of pleurodesis (on a scale of 0 to 4) after the injection of 50, 100, 200, and 400 mg/kg of talc was 1.1 +/- 0.9, 1.5 +/- 1.1, 2.7 +/- 0.6, and 3.4 +/- 0.5, respectively. The degree of microscopic fibrosis similarly increased with increasing doses of talc. These scores were similar to those we have reported with the tetracycline derivatives. In contrast to the results with tetracycline derivatives, none of the rabbits developed fibrothorax or hemothorax. From this study, we conclude that talc in a slurry is a very effective pleural sclerosant in rabbits and does not produce hemothoraces as do the tetracycline derivatives.

Minocycline is as effective as tetracycline in inducing pleural fibrosis, but the long-term pleural changes induced by minocycline are unknown. The objective of this study was to evaluate in rabbits the evolution of the pleural changes induced by the intrapleural instillation of minocycline. Under light anesthesia, minocycline at 10 mg/kg in a total volume of 2 ml of bacteriostatic saline solution was injected into the right pleural space of 25 male rabbits. The animals were sacrificed in groups of five at 15 d and 1, 2, 4, and 6 mo. Macroscopic and microscopic examinations of the pleura were performed for evidence of pleural fibrosis and inflammation. Similarly, the underlying lung was also examined for microscopic alveolar fibrosis and inflammation. During the 6-mo observation period there was no significant change in the degree of pleural fibrosis. In contrast, microscopic pleural inflammation, alveolar fibrosis, and alveolar inflammation all decreased significantly over the observation period. In conclusion, intrapleural minocycline injection results in persistent pleural fibrosis at 6 mo. It remains to be determined whether the pleural fibrosis will persist beyond this period.

Parenteral tetracycline, one of the most commonly used agents for producing pleurodesis, is no longer available because of stricter regulations governing the manufacturing process. The objective of this project was to determine whether minocycline, a tetracycline derivative, is an effective sclerosant in an experimental model in rabbits. We also studied the relationship of the dose and the volume injected to the degree of pleurodesis. The following medications were instilled intrapleurally in anesthetized male rabbits: tetracycline, 35 mg/kg; or minocycline, 4, 7, 10, or 20 mg/kg, diluted to a total volume of 1 or 2 ml of bacteriostatic saline solution; or minocycline, 40 mg/kg, diluted to a total volume of 2 ml of the solution. Twenty-eight days after the instillation, the animals were killed. The pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The degree of pleurodesis grossly and microscopically after the injection of 7, 10, 20, or 40 mg/kg of minocycline was comparable to that after the injection of 35 mg/kg of tetracycline, while the dose of 4 mg/kg was less effective. In the animals who received the higher doses of minocycline intrapleurally (ie > or = 20 mg/kg), there was an excess mortality both early (chi 2 = 3.61, 0.05 < p < 0.10) and late (chi 2 = 11.0, p < 0.005) which appeared to be related to the development of hemothorax. The intrapleural injection of the tetracycline derivatives was significantly (p < 0.05) more effective when the total volume of the solution was 2 ml rather than 1 ml. The present study demonstrates that minocycline is an effective agent for producing pleurodesis in the rabbit. Minocycline given intrapleurally at doses of 7 mg/kg or above is comparable to tetracycline, 35 mg/kg. Higher doses of minocycline (> or = 20 mg/kg) produce a high mortality that seems to be related to hemothorax. Since, in humans, a large experience confirms only 20 mg/kg of tetracycline is needed to produce adequate pleurodesis safely, we recommend a dose of 4 mg/kg of minocycline for the production of pleurodesis.