Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response

Details

Serval ID
serval:BIB_92FEAC3600A6
Type
Article: article from journal or magazin.
Collection
Publications
Title
Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response
Journal
Respir Res
Author(s)
Robriquet L., Collet F., Tournoys A., Prangere T., Neviere R., Fourrier F., Guery B. P.
ISSN
1465-993X (Electronic)
ISSN-L
1465-9921
Publication state
Published
Issued date
2006
Volume
7
Pages
41
Language
english
Notes
Robriquet, Laurent
Collet, Francois
Tournoys, Antoine
Prangere, Thierry
Neviere, Remi
Fourrier, Francois
Guery, Benoit P
eng
Comparative Study
England
Respir Res. 2006 Mar 22;7:41. doi: 10.1186/1465-9921-7-41.
Abstract
BACKGROUND: Acute lung injury (ALI) induces a coagulation/fibrinolysis imbalance and leads to fibrin deposition. The protein C pathway is an important regulator of the coagulation system and reduces the inflammatory response. The aim of the study was to examine the effects of recombinant human activated protein C (rhAPC) in the early phase of Pseudomonas aeruginosa (Pa)-induced lung injury. METHODS: The study was conducted in vivo on a rat model of Pa-induced ALI. Continuous intravenous (IV) rhAPC was administrated simultaneously with intratracheal (IT) Pa. We instilled into the airspaces a 5% bovine albumin solution with 1 mu(Ci of (125)I-albumin and injected IV 1 mu(Ci of (111)In-albumin to measure lung liquid clearance (LLC) and endothelial injury. Cytokines levels (TNFalpha and IL-6) and thrombin-antithrombin (TAT) complexes were measured in blood and bronchoalveolar lavage fluid (BALF) at 4 hours. Four groups were compared: control (CTR), pneumonia (PNP) receiving IT Pa (0.5 ml/kg of 1 x 10(9) cfu), APC: IV rhAPC (300 microg/kg/h), A-PNP: IT Pa /IV rhAPC. RESULTS: Alveolar-capillary permeability was increased in the PNP versus the CTR group (0.28 +/- 0.08 vs. 0.03 +/- 0.01, p < 0.05). IV rhAPC in Pa-induced ALI led to further injury (0.47 +/- 0.17 vs. 0.28 +/- 0.08, p = 0.2). The LLC was significantly decreased in the A-PNP group compared to PNP group (9.1 +/- (4.3% vs. 33.4 +/- 2.6%, p < 0.05). The lung wet to dry weight ratio was significantly increased in the PNP group (4.62 +/- 0.31) compared to the CTR group (3.87 +/- 0.22, p < 0.05). IV rhAPC administration tends to increase this parameter in Pa-induced ALI (5.80 +/- 0.66, p = 0.07). These findings were associated with a loss of inflammatory response compartmentalization measured by TNFalpha and IL-6 systemic levels. TAT complexes in BALF were increased in the A-PNP group (23.17 +/- 2.89 ng/ml) compared to the CTR group (0.92 +/- 0.17 ng/ml, p < 0.05) and the PNP group (11.06 +/- 2.76 ng/ml, p < 0.05). CONCLUSION: rhAPC reduces LLC following Pa-induced ALI and may influence pulmonary edema formation. The early massive fibrin formation is probably beneficial in ALI limiting both the extent of injury and permeability disorders.
Keywords
Animals, Antithrombin III/metabolism, Blood Coagulation/drug effects, Bronchoalveolar Lavage Fluid/chemistry/cytology/microbiology, Disease Models, Animal, Extravascular Lung Water/*drug effects/metabolism, Fibrinolytic Agents/administration & dosage/*therapeutic use, Inflammation/*metabolism/microbiology/pathology, Infusions, Intravenous, Interleukin-6/metabolism, Lung/metabolism/microbiology/pathology, Male, Neutrophils/drug effects/pathology, Oxygen/metabolism, Peptide Hydrolases/metabolism, Pneumonia, Bacterial/metabolism/microbiology/pathology, Protein C/administration & dosage/genetics/*pharmacology, Pseudomonas aeruginosa/isolation & purification, Rats, Rats, Sprague-Dawley, Recombinant Proteins/administration & dosage/pharmacology, Respiratory Distress Syndrome/*metabolism/microbiology/pathology, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Create date
29/04/2021 9:59
Last modification date
30/04/2021 5:38
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