Tissue plasminogen activator potently stimulates pleural effusion via a monocyte chemotactic protein-1-dependent mechanism
MetadataShow full item record
Copyright © 2015 by the American Thoracic Society. Pleural infection is common. Evacuation of infected pleural fluid is essential for successful treatment, but it is often difficult because of adhesions/loculations within the effusion and the viscosity of the fluid. Intrapleural delivery of tissue plasminogen activator (tPA) (to break the adhesions) and deoxyribonuclease (DNase) (to reduce fluid viscosity) has recently been shown to improve clinical outcomes in a large randomized study of pleural infection. Clinical studies of intrapleural fibrinolytic therapy have consistently shown subsequent production of large effusions, the mechanism(s) of which are unknown. We aimed to determine the mechanism by which tPA induces exudative fluid formation. Intrapleural tPA, with or without DNase, significantly induced pleural fluid accumulation in CD1 mice (tPA alone: median [interquartile range], 53.5 [30-355] µl) compared with DNase alone or vehicle controls (both, 0.0 [0.0-0.0] µl) after 6 hours. Fluid induction was reproduced after intrapleural delivery of streptokinase and urokinase, indicating a class effect. Pleural fluid monocyte chemotactic protein (MCP)-1 levels strongly correlated with effusion volume (r = 0.7302; P = 0.003), and were significantly higher than MCP-1 levels in corresponding sera. Mice treated with anti-MCP-1 antibody (P < 0.0001) or MCP-1 receptor antagonist (P = 0.0049) demonstrated a significant decrease in tPA-induced pleural fluid formation (by up to 85%). Our data implicate MCP-1 as the key molecule governing tPA-induced fluid accumulation. The role of MCP-1 in the development of other exudative effusions warrants examination.
Showing items related by title, author, creator and subject.
Protocol of the PLeural Effusion and Symptom Evaluation (PLEASE) study on the pathophysiology of breathlessness in patients with symptomatic pleural effusionsThomas, R.; Azzopardi, M.; Muruganandan, S.; Read, C.; Murray, K.; Eastwood, Peter; Jenkins, Susan; Singh, B.; Lee, Y. (2016)Introduction: Pleural effusion is a common clinical problem that can complicate many medical conditions. Breathlessness is the most common symptom of pleural effusion of any cause and the most common reason for pleural ...
Thomas, R.; Jenkins, Susan; Eastwood, Peter; Gary Lee, Y.; Singh, B. (2015)Purpose of review: Pleural effusions have a major impact on the cardiorespiratory system. This article reviews the pathophysiological effects of pleural effusions and pleural drainage, their relationship with breathlessness, ...
The effects of pleural fluid drainage on respiratory function in mechanically ventilated patients after cardiac surgeryBrims, Fraser; Davies, M.; Elia, A.; Griffiths, M. (2015)BACKGROUND: Pleural effusions occur commonly after cardiac surgery and the effects of drainage on gas exchange in this population are not well established. We examined pulmonary function indices following drainage of ...