Document Detail

Neutrophil stimulation with granulocyte colony-stimulating factor worsens ventilator-induced lung injury and mortality in rats.
MedLine Citation:
PMID:  16249674     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Based on the association between the neutrophil and ventilator-induced lung injury, the authors hypothesized that neutrophil inhibition with fucoidin would be beneficial and stimulation with granulocyte colony-stimulating factor (G-CSF) would be harmful in a rat model of lethal ventilator-induced lung injury. METHODS: Animals (n = 111) were randomly assigned to be pretreated with fucoidin, G-CSF, or placebo (control) before 4 h of low-tidal-volume (10 ml/kg) or high-tidal-volume (40 ml/kg) mechanical ventilation. RESULTS: All low-volume animals survived. With high volumes, compared with controls, fucoidin did not improve survival (3 of 20 control animals and 5 of 20 fucoidin animals died; P = 0.51) but G-CSF significantly worsened it (18 of 22 animals died; P < 0.001). Circulating neutrophils were increased early with G-CSF and late with fucoidin with low and high tidal volumes (P < 0.05 for each treatment and tidal volume). Fucoidin decreased lung neutrophils, but these were only significant with high tidal volumes, whereas G-CSF increased lung neutrophils but only significantly with low tidal volumes (P < or = 0.01 for each). Fucoidin did not alter any cardiopulmonary measure significantly. Compared with control, G-CSF increased airway pressures with high tidal volumes and worsened lung edema and arterial oxygen with both tidal volumes (P < 0.05 for each). CONCLUSIONS: In this model, neutrophil stimulation by G-CSF increased lung dysfunction and with high tidal volumes worsened survival rates. Extrapolated clinically, neutrophil stimulation either by agents such as G-CSF or conditions such as sepsis may aggravate ventilator-induced lung injury.
Waheedullah Karzai; Xizhong Cui; Norbert Heinicke; Christian Niemann; Eric P Gerstenberger; Rosaly Correa; Steven Banks; Bjoern Mehlhorn; Frank Bloos; Konrad Reinhart; Peter Q Eichacker
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anesthesiology     Volume:  103     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-26     Completed Date:  2006-01-25     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  996-1005     Citation Subset:  AIM; IM    
Department of Anesthesiology and Critical Care Medicine, Friedrich-Schiller-University Hospital, Jena, Germany.
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MeSH Terms
Anti-Bacterial Agents / pharmacology
Bronchoalveolar Lavage Fluid / cytology
Granulocyte Colony Stimulating Factor, Recombinant / pharmacology*
Hemodynamics / drug effects
Interleukin-6 / metabolism
Leukocyte Count
Lung / pathology
Lung Diseases / mortality,  physiopathology,  prevention & control*
Neutrophils / drug effects*,  pathology
Paralysis / chemically induced
Polysaccharides / pharmacology
Pulmonary Edema / pathology
Rats, Wistar
Respiration, Artificial / adverse effects*,  mortality*
Respiratory Function Tests
Stimulation, Chemical
Tumor Necrosis Factor-alpha / metabolism
Ventilators, Mechanical / adverse effects*
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Granulocyte Colony Stimulating Factor, Recombinant; 0/Interleukin-6; 0/Polysaccharides; 0/Tumor Necrosis Factor-alpha; 9072-19-9/fucoidan

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