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
Institution
Title
Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response.
Journal
Respiratory research
ISSN
1465-993X (Electronic)
ISSN-L
1465-9921
Publication state
Published
Issued date
22/03/2006
Peer-reviewed
Oui
Volume
7
Number
1
Pages
41
Language
english
Notes
Publication types: Comparative Study ; Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
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.
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.
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).
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.
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.
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).
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, Bronchoalveolar Lavage Fluid/cytology, Bronchoalveolar Lavage Fluid/microbiology, Disease Models, Animal, Extravascular Lung Water/drug effects, Extravascular Lung Water/metabolism, Fibrinolytic Agents/administration & dosage, Fibrinolytic Agents/therapeutic use, Inflammation/metabolism, Inflammation/microbiology, Inflammation/pathology, Infusions, Intravenous, Interleukin-6/metabolism, Lung/metabolism, Lung/microbiology, Lung/pathology, Male, Neutrophils/drug effects, Neutrophils/pathology, Oxygen/metabolism, Peptide Hydrolases/metabolism, Pneumonia, Bacterial/metabolism, Pneumonia, Bacterial/microbiology, Pneumonia, Bacterial/pathology, Protein C/administration & dosage, Protein C/genetics, Protein C/pharmacology, Pseudomonas aeruginosa/isolation & purification, Rats, Rats, Sprague-Dawley, Recombinant Proteins/administration & dosage, Recombinant Proteins/pharmacology, Respiratory Distress Syndrome/metabolism, Respiratory Distress Syndrome/microbiology, Respiratory Distress Syndrome/pathology, Tumor Necrosis Factor-alpha/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
29/04/2021 10:59
Last modification date
17/07/2023 14:25
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