Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models

Andrey A. Komissarov, Galina Florova, Ali O. Azghani, Ann Buchanan, Jake Boren, Timothy Allen, Najib M. Rahman, Kathleen Koenig, Mignote Chamiso, Sophia Karandashova, James Henry, Steven Idell

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)389-399
Number of pages11
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume311
Issue number2
DOIs
StatePublished - Aug 1 2016

Keywords

  • Empyema
  • Fibrinolysis
  • Plasminogen activator inhibitor-1
  • Single chain urokinase
  • Tissue plasminogen activator

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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  • Cite this

    Komissarov, A. A., Florova, G., Azghani, A. O., Buchanan, A., Boren, J., Allen, T., Rahman, N. M., Koenig, K., Chamiso, M., Karandashova, S., Henry, J., & Idell, S. (2016). Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models. American Journal of Physiology - Lung Cellular and Molecular Physiology, 311(2), 389-399. https://doi.org/10.1152/ajplung.00171.2016