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(Chest. 2006;129:1577-1583.)
© 2006 American College of Chest Physicians

Tissue Plasminogen Activator Combined With Human Recombinant Deoxyribonuclease Is Effective Therapy for Empyema in a Rabbit Model*

Zhiwen Zhu, MD; Michael L. Hawthorne, MD; Yubiao Guo, MD; Wonder Drake, MD; Semra Bilaceroglu, MD, FCCP; Heather L. Misra, MD and Richard W. Light, MD, FCCP

* From the Departments of Pulmonary Medicine and Infectious Diseases, Vanderbilt University, Nashville, TN.

Correspondence to: Richard W. Light, MD, FCCP, Vanderbilt University Medical Center, T-1218 Medical Center North, Nashville, TN 37232; e-mail rlight98{at}yahoo.com

Abstract

Objectives: There have been no controlled studies to test the efficacy of tissue plasminogen activator (tPA) or recombinant human deoxyribonuclease (rhDNase) in the treatment of empyema. In vitro studies show that streptokinase without rhDNase does not liquefy empyemic material from rabbits. However, the combination of streptokinase and streptodornase and rhDNase have been shown to liquefy pus in vitro. The aim of this study was to determine if tPA or rhDNase, or a combination of the two, is more effective than saline solution in the treatment of empyema in rabbits.

Materials and methods: Empyema was induced in rabbits using 109 Pasteurella multicoda organisms in infusion agar injected via a surgically placed chest tube. Once empyema was verified, a blinded investigator administered one of four treatments via the chest tube: 3 mL of saline solution; 4 mg of alteplase (recombinant tPA); 1 mg of rhDNase; or 4 mg of alteplase and 1 mg of rhDNase. The rabbits received a treatment every 12 h following the initial for a total of six treatments. The animals were killed at day 10, and the degree of empyema and pleural peel was scored macroscopically on a scale of 0 to 4.

Results: The combination group had a significantly lower mean empyema score (1.83 ± 0.75) than did the saline solution group (3.86 ± 0.38, p = 0.001), rhDNase group (3.17 ± 0.75, p = 0.012), and alteplase group (3.71 ± 0.49, p = 0.02) [± SD]. The total volume of pleural fluid was markedly higher in the alteplase and rhDNase combination group (142 ± 79.1 mL) or the alteplase group (231 ± 78.0 mL) compared to either the rhDNase group (0.8 ± 1.6 mL) or the saline solution group (5.8 ± 14.0 mL).

Conclusion: The combination of alteplase and rhDNase is more effective in the treatment of rabbit empyema than either agent alone. The intrapleural injection of alteplase alone or in combination with rhDNase leads to the production of large amounts of pleural fluid.

Key Words: empyema • fibrinolytic • human recombinant deoxyribonuclease • pleural • rabbit • therapy • tissue plasminogen activator







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