Document Detail

Pretreatment with atorvastatin attenuates lung injury caused by high-stretch mechanical ventilation in an isolated rabbit lung model.
MedLine Citation:
PMID:  20308883     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: We hypothesized that pretreatment with atorvastatin improves alveolar capillary permeability and hemodynamics and, thus, confers protection against lung injury caused by high-stretch mechanical ventilation. METHODS: Twenty-four isolated sets of normal rabbit lungs were utilized. Treated animals received atorvastatin (20 mg/kg body weight/day by mouth) for 3 days before surgery. Lungs were perfused constantly (300 mL/min) and ventilated for 1 hr with pressure-control ventilation at either 23 (high pressure; resulting in tidal volume approximately 22 mL/kg) or 11 (low pressure; tidal volume approximately 10 mL/kg) cm H2O peak inspiratory pressure and positive end-expiratory pressure of 3 cm H2O. Four groups were examined: high pressure-no statin, high pressure-statin pretreatment, low pressure-no statin, and low pressure-statin pretreatment. RESULTS: The high-pressure-no statin group sustained more damage than the low-pressure groups. In high-pressure groups, lungs of statin-pretreated vs. no statin-pretreated animals sustained a significantly lower increase in ultrafiltration coefficient (an accurate marker of alveolar capillary permeability; high-pressure-statin pretreatment vs. high-pressure-no statin, -0.013 +/- 0.017 g/min/mm Hg/100g vs. 1.723 +/- 0.495 g/min/mm Hg/100g; p < .001), lower weight gain (i.e., less edema formation; 4.62 +/- 1.50 grams vs. 17.75 +/- 4.71 grams; p = .005), improved hemodynamics (i.e., lower increase in mean pulmonary artery pressure; 0.56 +/- 0.51 mm Hg vs. 5.62 +/- 1.52 mm Hg; p = .04), lower protein concentration in bronchoalveolar lavage fluid (p < .001), and fewer histologic lesions (p = .013). Apoptosis of lung parenchyma cells was not different (p = .97). There was no difference between low-pressure-statin pretreatment and low-pressure-no statin groups regarding these outcomes. CONCLUSION: In this model, atorvastatin improves alveolar capillary permeability and hemodynamics and, thus, attenuates lung injury caused by high-stretch mechanical ventilation.
Ilias I Siempos; Nikolaos A Maniatis; Petros Kopterides; Christina Magkou; Constantinos Glynos; Charis Roussos; Apostolos Armaganidis
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  38     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-21     Completed Date:  2010-05-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1321-8     Citation Subset:  AIM; IM    
G P Livanos and M Simou Laboratories, Evangelismos Hospital, University of Athens Medical School, Athens, Greece.
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MeSH Terms
Acute Lung Injury / etiology*,  physiopathology,  prevention & control
Hemodynamics / drug effects
Heptanoic Acids / pharmacology*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Lung / pathology,  physiopathology
Pulmonary Edema / prevention & control
Pyrroles / pharmacology*
Respiration, Artificial / adverse effects*
Respiratory Function Tests
Reg. No./Substance:
0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrroles; 110862-48-1/atorvastatin

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