- 作者：Pierre Raeven ; Georg Alexander Feichtinger ; Katrin Maria Weixelbaumer ; Simone Atzenhofer ; Heinz Redl ; Martijn Van Griensven ; Soheyl Bahrami ; Marcin Filip Osuchowski ; Marcin.Osuchowski@trauma.lbg.ac.at
- 关键词：PAI-1 ; plasminogen activator inhibitor type-1 ; CLP ; cecal ligation and puncture ; SUR ; surviving mice ; DIE ; dying mice ; LCVC ; left cranial vena cava ; t-PA ; tissue-type plasminogen activator ; u-PA ; urokinase-type plasminogen activator ; LPS ; lipopolysacchari
- 刊名：Thrombosis Research
- 出版年：2012
- 出版时间：May, 2012
- 年：2012
- 卷：129
- 期：5
- 页码：e238-e245
- 全文大小：849 K
class=""h4"">Introduction
Plasminogen activator inhibitor type 1 (PAI-1) co-induces septic coagulopathy. We aimed to characterize spatiotemporal PAI-1 gene/protein changes occurring in acute sepsis and tested whether PAI-1 fluctuations correlate with sepsis severity and early outcome.class=""h4"">Materials and Methods
Female mice underwent cecal ligation and puncture (CLP) in three experiments. I: mild (23G needle) CLP to compare circulating PAI-1 to its organ gene expression within 0-24 h. II: mild or severe (17G) CLP to asses differences in PAI-1 organ-specific expression and in coagulation/fibrinolysis. III: moderate (18G) CLP to characterize circulating PAI-1 in survivors (SUR), and to retrospectively compare it to dying (DIE) mice.
class=""h4"">Results
In mild sepsis, the trajectory of circulating PAI-1 (1089 ng/ml peak at 24 h) was identical to PAI-1 gene expression in the left cranial vena cava (LCVC; 39-fold peak at 24 h). PAI-1 expression rise was immediate (60-fold at 6 h) and sustained in the liver, but marginal in the kidney, lungs and heart. Body temperature decrease correlated with the PAI-1 expression increase in the liver (rho = ?#xA0;0.79), and blood (protein, rho = ?#xA0;0.53). Regardless of severity, PAI-1 gene expression remained unaltered except the LCVC where it was > 3-fold higher in 17G (vs. 23G). Severe sepsis extended activated partial thromboplastin/pro-thrombin time and increased circulating PAI-1, while antithrombin and fibrinogen decreased at 6 and/or 24 h (vs. 23G). Within 24 h of death, circulating PAI-1 in DIE was > 3-fold higher versus SUR.
class=""h4"">Conclusions
Polymicrobial sepsis caused a gradual circulating PAI-1 release and highly variable gene expression response pattern in organs. Only circulating PAI-1 and PAI-1 expression in the LCVC correlated with response severity and/or outcome.