Komissarov AA1,
Florova G2,
Azghani AO3,
Buchanan A2,
Boren J2,
Allen T4,
Rahman NM5,
Koenig K2,
Chamiso M2,
Karandashova S2,
Henry J2,
Idell S2.
- 1Department of Cellular and Molecular Biology of the University of Texas Health Science Center at Tyler, Tyler, Texas; andrey.komissarov@uthct.edu.
- 2Department of Cellular and Molecular Biology of the University of Texas Health Science Center at Tyler, Tyler, Texas;
- 3The University of Texas at Tyler, Tyler, Texas;
- 4Department of Pathology, The University of Texas Medical Branch, Galveston, Texas; and.
- 5Oxford Centre for Respiratory Medicine, Oxford University Hospitals, National Health Service Trust, Oxford, UK.
Abstract
The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP.
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