Skip to main content
. 2017 Aug 31;314(1):L54–L68. doi: 10.1152/ajplung.00579.2016

Fig. 12.

Fig. 12.

Changing plasminogen activator inhibitor-1 (PAI-1) activity affects intrapleural fibrinolytic therapy (IPFT) outcomes under conditions of slow fibrinolysis in the pleural space. Successful IPFT in tetracycline (TCN)-induced pleural injury in rabbits requires maintaining plasminogen-activating activity for 4–8 h (48). The minimal time necessary for effective fibrinolysis (4–8 h) is shown as a yellow zone between effective (green zone; >8 h) and ineffective (red zone; <4 h) IPFT outcomes. The rate of PAI-1-independent inactivation of uPA remains the same with different doses of prourokinase (scuPA; 46), shown as parallel solid lines, with the minimal effective dose in the middle. Fibrinolysis stops as soon as endogenous PAI-1 (black dashed line) inhibits the plasminogen activator(s) present (intercept of solid and dashed lines), which in turn determines outcomes for effective (yellow and green zones) and ineffective (red zone) IPFT. Neutralizing PAI-1 (blue arrow) decreases PAI-1 activity (blue dotted line). Consequently, an otherwise ineffective dose of scuPA (the lowest solid line) provides positive plasminogen-activating activity for >8 h (the intercept with the blue dotted line in the green zone), representing the increased efficacy of IPFT (decreasing the minimal effective dose). On the other hand, increasing the PAI-1 activity in the pleural space (red arrow) results in faster inhibition of intrapleural plasminogen activator (the intercept with the red dotted line in the red zone) and in ineffective IPFT with doses of scuPA that are normally effective. The efficacy of IPFT in tetracycline (TCN)-induced pleural injury was increased when PAI-1 was neutralized with MA-33B8 [Table 1; gross lung injury score (GLIS) = 3] or with monoclonal antibodies that redirect the PAI-1 mechanism toward the substrate branch (Fig. 1, ks; 25). The adverse effects of increased PAI-1 were observed during IPFT in the presence of MA-56A7C10 (Table 1; GLIS = 50), in animals subjected to serial computed chest tomography (48) and in rabbits with infectious pleural injury (empyema; 47). AU, arbitrary units; FT, fibrinolytic therapy.