Simvastatin attenuates neutrophil recruitment in one-lung ventilation model in rats

Acta Cir Bras. 2013 Apr;28(4):245-50. doi: 10.1590/s0102-86502013000400003.

Abstract

Purpose: To investigate the anti-inflammatory effects of simvastatin in rats undergoing one-lung ventilation (OLV) followed by lung re-expansion.

Methods: Male Wistar rats (n=30) were submitted to 1-h OLV followed by 1-h lung re-expansion. Treated group received simvastatin (40 mg/kg for 21 days) previous to OLV protocol. Control group received no treatment or surgical/ventilation interventions. Measurements of pulmonary myeloperoxidase (MPO) activity, pulmonary protein extravasation, and serum levels of cytokines and C-reactive protein (CRP) were performed.

Results: OLV significantly increased the MPO activity in the collapsed and continuously ventilated lungs (31% and 52% increase, respectively) compared with control (p<0.05). Treatment with simvastatin significantly reduced the MPO activity in the continuously ventilated lung but had no effect on lung edema after OLV. The serum IL-6 and CRP levels were markedly higher in OLV group, but simvastatin treatment failed to affect the production of these inflammatory markers. Serum levels of IL-1β, TNF-α and IL-10 remained below the detection limit in all groups.

Conclusions: In an experimental one-lung ventilation model pre-operative treatment with simvastatin reduces remote neutrophil infiltration in the continuously ventilated lung. Our findings suggest that simvastatin may be of therapeutic value in OLV-induced pulmonary inflammation deserving clinical investigations.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • C-Reactive Protein / analysis
  • Cytokines / blood
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Lung / drug effects
  • Lung / physiopathology
  • Male
  • Models, Animal
  • Neutrophil Infiltration / drug effects*
  • One-Lung Ventilation / methods*
  • Peroxidase / physiology
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • Simvastatin / pharmacology*
  • Simvastatin / therapeutic use
  • Thoracic Surgical Procedures / adverse effects
  • Thoracic Surgical Procedures / methods

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • C-Reactive Protein
  • Simvastatin
  • Peroxidase