Pretreatment with atorvastatin ameliorates lung injury caused by high-pressure/high-tidal-volume mechanical ventilation in isolated normal rabbit lungs

Introduction

Previous animal studies revealed that administration of statins ameliorates lung injury following endotoxin exposure or ischemia-reperfusion. In this experiment, we endeavored to investigate whether pretreatment with atorvastatin confers protection from lung injury caused by high-pressure/high-tidal-volume ventilation.

Methods

Twenty-four isolated sets of normal rabbit lungs were utilized. Treated animals received atorvastatin (20 mg/kg body weight/day per os) for 3 days before surgery. All isolated lungs were perfused (constant flow, 300 ml/min) and ventilated for 1 hour with pressure control ventilation at either 23 cmH₂O (high-pressure, injurious ventilation) or 11 cmH₂O (low-pressure, noninjurious ventilation) peak static pressure and positive end-expiratory pressure of 3 cmH₂O. Four groups of six lung sets each were examined: HPC (high pressure, no statin), HPS (high pressure, statin pretreatment), LPC (low pressure, no statin), and LPS (low pressure, statin pretreatment). Changes (from baseline to the end of ventilation) in the ultrafiltration coefficient (ΔK_{f, c}; pulmonary capillary permeability), weight gain (ΔW; edema formation) and histological lesions (hemorrhage) were used as indices of lung damage.

Results

At baseline, the compared groups did not differ with regard to K_{f, c} (P = 0.3). At the end of ventilation, the HPC group suffered greater ΔK_{f, c} (P < 0.001) and greater ΔW (P < 0.001) than both the LPC and LPS groups. In contrast, the HPS group did not differ from both the LPS and LPC groups regarding these variables (P > 0.4). In the HPC and HPS groups, lungs with as opposed to those without statin pretreatment experienced a significantly lower ΔK_{f, c} (-0.013 ± 0.016 versus 1.723 ± 0.495 g/min/cmH₂O/100 g; P = 0.0006) and lower ΔW (4.62 ± 1.50 versus 17.75 ± 4.71 g; P = 0.007). This was also the case for the histological lesions.

Conclusion

In an ex vivo model of ventilator-induced lung injury, pretreatment with atorvastatin attenuates lung injury following high-pressure/high-tidal-volume ventilation.