C Strange, MH Baumann, SA Sahn and S Idell
Department of Medicine, Medical University of South Carolina, Charleston 29425.

Extravascular fibrin deposition is common at sites of pleural injury and has been related to loculation of pleural fluids. Although thrombolytic therapy has been used to treat pleural loculations, it has not been compared with pleural administration of anticoagulant therapy. We therefore tested interventional strategies designed to compare the relative effects of in vivo anticoagulation or supplemented fibrinolysis on pleural injury, and to characterize the local tissue responses to these modalities. Early intrapleural instillation of saline (Group 1), heparin 1,000 IU (Group 2), or urokinase (uPA) 1,500 IU (Group 3) every 12 h for 3 d was used to interrupt pleural adhesion formation and pleural fibrosis induced by tetracycline hydrochloride in rabbits. Procoagulant and fibrinolytic activities were determined in pleural effusion samples obtained serially every 12 h after the last administered intrapleural dose. Pleural fluid procoagulant activity was blocked by intrapleural heparin (p < 0.001), but plasminogen-dependent fibrinolytic activity was rarely increased by intrapleural urokinase. Most plasminogen activator activity in the pleural fluids was found at high-molecular-weight regions by enzymography, suggesting that it was bound to inhibitor(s). Pathologic analysis at 14 d demonstrated that the number of pleural adhesions in the heparin (8.4 +/- 3.4, mean +/- standard error) and uPA groups (6.1 +/- 2.5) was less than in saline- treated tetracycline controls (20.7 +/- 4.7) (both p < 0.02). Visceral pleural thickness did not differ between groups (p = NS). We conclude that intrapleural heparin or uPA are equally effective in decreasing intrapleural adhesions in tetracycline-induced pleural injury. The data indicate that early anticoagulation or fibrinolytic intervention can attenuate subsequent pleural symphysis in this model.

This article has been cited by other articles:

				S. Idell, T. Allen, S. Chen, K. Koenig, A. Mazar, and A. Azghani Intrapleural activation, processing, efficacy, and duration of protection of single-chain urokinase in evolving tetracycline-induced pleural injury in rabbits Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L25 - L32. [Abstract] [Full Text] [PDF]

				V. Getman, E. Devyatko, E. Wolner, S. Aharinejad, and M. R. Mueller Fleece bound sealing prevents pleural adhesions Interactive CardioVascular and Thoracic Surgery, June 1, 2006; 5(3): 243 - 246. [Abstract] [Full Text] [PDF]

				L. Erkan, S. Fyndyk, O. Uzun, A. G. Atycy, and R. W. Light A New Radiologic Appearance of Pulmonary Thromboembolism: Multiloculated Pleural Effusions Chest, July 1, 2004; 126(1): 298 - 302. [Abstract] [Full Text] [PDF]

				S. Chuang-Tsai, T. H. Sisson, N. Hattori, C. G. Tsai, N. M. Subbotina, K. E. Hanson, and R. H. Simon Reduction in Fibrotic Tissue Formation in Mice Genetically Deficient in Plasminogen Activator Inhibitor-1 Am. J. Pathol., August 1, 2003; 163(2): 445 - 452. [Abstract] [Full Text] [PDF]

				V. B. Antony Fibrinolysis in the Pleural Space: Breaking the Bonds That Bind Am. J. Respir. Crit. Care Med., October 1, 2002; 166(7): 909 - 910. [Full Text]

				S. Idell, A. Mazar, D. Cines, A. Kuo, G. Parry, S. Gawlak, J. Juarez, K. Koenig, A. Azghani, W. Hadden, et al. Single-Chain Urokinase Alone or Complexed to Its Receptor in Tetracycline-induced Pleuritis in Rabbits Am. J. Respir. Crit. Care Med., October 1, 2002; 166(7): 920 - 926. [Abstract] [Full Text]

				S. IDELL, A. P. MAZAR, P. BITTERMAN, S. MOHLA, and A. L. HARABIN Fibrin Turnover in Lung Inflammation and Neoplasia Am. J. Respir. Crit. Care Med., February 1, 2001; 163(2): 578 - 584. [Full Text]

				D. BOUROS, S. SCHIZA, N. TZANAKIS, G. CHALKIADAKIS, J. DROSITIS, and N. SIAFAKAS Intrapleural Urokinase versus Normal Saline in the Treatment of Complicated Parapneumonic Effusions and Empyema . A Randomized, Double-Blind Study Am. J. Respir. Crit. Care Med., January 1, 1999; 159(1): 37 - 42. [Abstract] [Full Text]