RGD Reference Report - Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response. - Rat Genome Database

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

Authors: Robriquet, L  Collet, F  Tournoys, A  Prangere, T  Neviere, R  Fourrier, F  Guery, BP 
Citation: Robriquet L, etal., Respir Res. 2006 Mar 22;7:41.
RGD ID: 11100043
Pubmed: PMID:16553944   (View Abstract at PubMed)
PMCID: PMC1435891   (View Article at PubMed Central)
DOI: DOI:10.1186/1465-9921-7-41   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PROCHumanAcute Lung Injury treatmentIDA associated with Pseudomonas InfectionsRGD 
ProcRatAcute Lung Injury treatmentISOPROC (Homo sapiens)associated with Pseudomonas InfectionsRGD 
ProcMouseAcute Lung Injury treatmentISOPROC (Homo sapiens)associated with Pseudomonas InfectionsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Proc  (protein C, inactivator of coagulation factors Va and VIIIa)

Genes (Mus musculus)
Proc  (protein C)

Genes (Homo sapiens)
PROC  (protein C, inactivator of coagulation factors Va and VIIIa)


Additional Information