Abstract | OBJECTIVE: SETTING: University laboratory. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: MEASUREMENTS AND MAIN RESULTS: Mortality was 25% with bleomycin only and 50% with bleomycin + granulocyte colony-stimulating factor. Granulocyte colony-stimulating factor increased alveolar neutrophil recruitment, pulmonary edema, and lung myeloperoxidase activity on day 4. Lung static compliance on day 15 was severely decreased with bleomycin alone and showed a further significant decrease when granulocyte colony-stimulating factor was added (controls, 3.85 +/- 0.14 mL/kPa; bleomycin, 1.44 +/- 0.06 mL/kPa; and bleomycin + granulocyte colony-stimulating factor, 0.65 +/- 0.09 mL/kPa; control vs. bleomycin, p <.0001; and bleomycin vs. bleomycin + granulocyte colony-stimulating factor, p =.0003). Lung morphology with bleomycin + granulocyte colony-stimulating factor showed, in addition to the changes observed with bleomycin alone, four patterns indicating more severe disease: honeycomb foci, pleural thickening with hyaline fibrosis, interstitial granuloma with increased number of macrophages but not neutrophils, and established interstitial fibrosis. Lidocaine, which prevents neutrophil adhesion to endothelial cells, inhibited granulocyte colony-stimulating factor-related exacerbation of acute lung injury (bronchoalveolar lavage fluid cells and pulmonary edema) and pulmonary fibrosis (lung static compliance and morphologic changes). CONCLUSIONS:
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Authors | Elie Azoulay, Sabine Herigault, Micheline Levame, Laurent Brochard, Benoît Schlemmer, Alain Harf, Christophe Delclaux |
Journal | Critical care medicine
(Crit Care Med)
Vol. 31
Issue 5
Pg. 1442-8
(May 2003)
ISSN: 0090-3493 [Print] United States |
PMID | 12771616
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibiotics, Antineoplastic
- Bleomycin
- Granulocyte Colony-Stimulating Factor
- Lidocaine
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Topics |
- Animals
- Antibiotics, Antineoplastic
(administration & dosage, adverse effects)
- Bleomycin
(administration & dosage, adverse effects)
- Cell Adhesion
(drug effects)
- Disease Models, Animal
- Drug Evaluation, Preclinical
- Drug Synergism
- Drug Therapy, Combination
- Granulocyte Colony-Stimulating Factor
(administration & dosage, adverse effects, physiology)
- Instillation, Drug
- Lidocaine
(pharmacology, therapeutic use)
- Lung Compliance
(drug effects)
- Male
- Neutrophil Activation
(drug effects)
- Neutrophil Infiltration
(drug effects)
- Pulmonary Alveoli
(drug effects)
- Pulmonary Fibrosis
(chemically induced, drug therapy, immunology, pathology)
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Respiratory Distress Syndrome
(chemically induced, drug therapy, immunology, pathology)
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