June 15, 1999Circulation
Plasminogen Activator Inhibitor-1 Is a Major Determinant of Arterial Thrombolysis Resistance
Key result
PAI-1 deficiency significantly increased reperfusion rates after tPA infusion compared to wild-type mice (100% vs 20%, P=0.0006), demonstrating PAI-1 is a major determinant of thrombolysis resistance.
Why the study?
Does PAI-1 deficiency improve tPA-mediated arterial thrombolysis in a murine carotid injury model?
Population
Wild-type mice and PAI-1-deficient mice with ferric chloride-induced platelet-rich carotid thrombi
Comparison
PAI-1 deficiency treated with tPA, heparin, and… vs Wild-type mice treated with the same tPA…
Design
Preclinical
Authors
Discussion
Loading...
Member takes
Implication
PAI-1 inhibition may enhance tPA reperfusion; hypothesis-generating in mice, human trials required before any practice change.
Structured PICO
Does PAI-1 deficiency improve tPA-mediated arterial thrombolysis in a murine carotid injury model?
P
Population
22 mice (11 wild-type and 11 PAI-1-deficient) with ferric chloride-induced platelet-rich thrombi.
E
Exposure
PAI-1 deficiency (PAI-1 -/- mice) treated with tPA (20 or 100 microg/kg/min), heparin (200 U/kg bolus, 70 U/kg/h drip), and human plasminogen (50 mg/kg)
C
Comparator
Wild-type mice (PAI-1 +/+) treated with the same tPA, heparin, and human plasminogen regimen
O
Outcome
Reperfusion rate and reperfusion timesurrogate
Main Result
Absolute Event Rate: 100% vs 20%
p-value: p=0.0006
PAI-1 is a major determinant of resistance to tPA-mediated lysis in platelet-rich arterial thrombi, suggesting that strategies to inhibit PAI-1 may enhance thrombolysis.
Cite This Study
Zhu et al. (1999) studied Platelet-rich arterial thrombi (n=22). PAI-1 deficiency vs. Wild-type mice (PAI-1 +/+) was evaluated on Reperfusion after tPA 20 microg/kg/min (p=0.0006). PAI-1 deficiency significantly increased reperfusion rates after tPA infusion compared to wild-type mice (100% vs 20%, P=0.0006), demonstrating PAI-1 is a major determinant of thrombolysis resistance.