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Plasminogen activator inhibitor-type I gene deficient mice show reduced influx of neutrophils in ventilator-induced lung injury.

Wolthuis EK, Vlaar AP, Hofstra JJ, Roelofs JJ, de Waard V, Juffermans NP, Schultz MJ - Crit Care Res Pract (2011)

Bottom Line: Ventilator-induced lung injury (VILI) is associated with inhibition of the fibrinolytic system secondary to increased production of plasminogen activator inhibitor- (PAI-)1.Ventilation resulted in pulmonary coagulopathy and inflammation, with more injury following ventilation with HV(T) as compared to LV(T).These data indicate that a defect fibrinolytic response attenuates recruitment of neutrophils in VILI.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

ABSTRACT
Ventilator-induced lung injury (VILI) is associated with inhibition of the fibrinolytic system secondary to increased production of plasminogen activator inhibitor- (PAI-)1. To determine the role of PAI-1 on pulmonary coagulopathy and inflammation during mechanical ventilation, PAI-1 gene-deficient mice and their wild-type littermates were anesthetized (control), or anesthetized, tracheotomized and subsequently ventilated for 5 hours with either low tidal volumes (LV(T)) or high tidal volumes (HV(T)). VILI was assessed by pulmonary coagulopathy, lung wet-to-dry ratios, total protein level in bronchoalveolar lavage fluid, neutrophil influx, histopathology, and pulmonary and plasma cytokine levels. Ventilation resulted in pulmonary coagulopathy and inflammation, with more injury following ventilation with HV(T) as compared to LV(T). In PAI-1 gene-deficient mice, the influx of neutrophils in the pulmonary compartment was attenuated, while increased levels of pulmonary cytokines were found. Other endpoints of VILI were not different between PAI-1 gene-deficient and wild-type mice. These data indicate that a defect fibrinolytic response attenuates recruitment of neutrophils in VILI.

No MeSH data available.


Related in: MedlinePlus

Systemic levels of interleukin- (IL-) 6, and keratinocyte-derived chemokine (KC) in plasma in anesthetized nonventilated control (C) mice, mice ventilated with LVT or HVT. Mice were either PAI-1 deficient (PAI-1−/−, open symbols) or wild type (Wt, closed symbols). Data are represented as individual data with a median. * indicates statistical significant difference compared to Wt.
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fig5: Systemic levels of interleukin- (IL-) 6, and keratinocyte-derived chemokine (KC) in plasma in anesthetized nonventilated control (C) mice, mice ventilated with LVT or HVT. Mice were either PAI-1 deficient (PAI-1−/−, open symbols) or wild type (Wt, closed symbols). Data are represented as individual data with a median. * indicates statistical significant difference compared to Wt.

Mentions: Plasma levels of IL-6 and KC were elevated in both ventilation groups as compared to control (P < 0.001 for both LVT and HVT mice), with higher levels in HVT mice (P < 0.001; Figure 5). Plasma levels of IL-6 were lower in PAI-1−/− mice in the LVT group as compared to Wt mice (P = 0.009; Figure 5). HVT mice demonstrated a trend for lower IL-6 levels in PAI-1−/− mice (P = 0.065). For plasma levels of KC, no differences were observed between PAI-1−/−mice and Wt mice.


Plasminogen activator inhibitor-type I gene deficient mice show reduced influx of neutrophils in ventilator-induced lung injury.

Wolthuis EK, Vlaar AP, Hofstra JJ, Roelofs JJ, de Waard V, Juffermans NP, Schultz MJ - Crit Care Res Pract (2011)

Systemic levels of interleukin- (IL-) 6, and keratinocyte-derived chemokine (KC) in plasma in anesthetized nonventilated control (C) mice, mice ventilated with LVT or HVT. Mice were either PAI-1 deficient (PAI-1−/−, open symbols) or wild type (Wt, closed symbols). Data are represented as individual data with a median. * indicates statistical significant difference compared to Wt.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140778&req=5

fig5: Systemic levels of interleukin- (IL-) 6, and keratinocyte-derived chemokine (KC) in plasma in anesthetized nonventilated control (C) mice, mice ventilated with LVT or HVT. Mice were either PAI-1 deficient (PAI-1−/−, open symbols) or wild type (Wt, closed symbols). Data are represented as individual data with a median. * indicates statistical significant difference compared to Wt.
Mentions: Plasma levels of IL-6 and KC were elevated in both ventilation groups as compared to control (P < 0.001 for both LVT and HVT mice), with higher levels in HVT mice (P < 0.001; Figure 5). Plasma levels of IL-6 were lower in PAI-1−/− mice in the LVT group as compared to Wt mice (P = 0.009; Figure 5). HVT mice demonstrated a trend for lower IL-6 levels in PAI-1−/− mice (P = 0.065). For plasma levels of KC, no differences were observed between PAI-1−/−mice and Wt mice.

Bottom Line: Ventilator-induced lung injury (VILI) is associated with inhibition of the fibrinolytic system secondary to increased production of plasminogen activator inhibitor- (PAI-)1.Ventilation resulted in pulmonary coagulopathy and inflammation, with more injury following ventilation with HV(T) as compared to LV(T).These data indicate that a defect fibrinolytic response attenuates recruitment of neutrophils in VILI.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

ABSTRACT
Ventilator-induced lung injury (VILI) is associated with inhibition of the fibrinolytic system secondary to increased production of plasminogen activator inhibitor- (PAI-)1. To determine the role of PAI-1 on pulmonary coagulopathy and inflammation during mechanical ventilation, PAI-1 gene-deficient mice and their wild-type littermates were anesthetized (control), or anesthetized, tracheotomized and subsequently ventilated for 5 hours with either low tidal volumes (LV(T)) or high tidal volumes (HV(T)). VILI was assessed by pulmonary coagulopathy, lung wet-to-dry ratios, total protein level in bronchoalveolar lavage fluid, neutrophil influx, histopathology, and pulmonary and plasma cytokine levels. Ventilation resulted in pulmonary coagulopathy and inflammation, with more injury following ventilation with HV(T) as compared to LV(T). In PAI-1 gene-deficient mice, the influx of neutrophils in the pulmonary compartment was attenuated, while increased levels of pulmonary cytokines were found. Other endpoints of VILI were not different between PAI-1 gene-deficient and wild-type mice. These data indicate that a defect fibrinolytic response attenuates recruitment of neutrophils in VILI.

No MeSH data available.


Related in: MedlinePlus