Atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats

Abstract

Atelectasis can impair arterial oxygenation and decrease lung compliance. However, the effects of atelectasis on endotoxemic lungs during ventilation have not been well studied. We hypothesized that ventilation at low volumes below functional residual capacity (FRC) would accentuate lung injury in lipopolysaccharide (LPS)-pretreated rats. LPS-pretreated rats were ventilated with room air at 85 breaths/min for 2 hr at a tidal volume of 10 mL/kg with or without thoracotomy. Positive end-expiratory pressure (PEEP) was applied to restore FRC in the thoracotomy group. While LPS or thoracotomy alone did not cause significant injury, the combination of endotoxemia and thoracotomy caused significant hypoxemia and hypercapnia. The injury was observed along with a marked accumulation of inflammatory cells in the interstitium of the lungs, predominantly comprising neutrophils and mononuclear cells. Immunohistochemistry showed increased inducible nitric oxide synthase (iNOS) expression in mononuclear cells accumulated in the interstitium in the injury group. Pretreatment with PEEP or an iNOS inhibitor (1400 W) attenuated hypoxemia, hypercapnia, and the accumulation of inflammatory cells in the lung. In conclusion, the data suggest that atelectasis induced by thoracotomy causes lung injury during mechanical ventilation in endotoxemic rats through iNOS expression.

Fig. 1

Blood gas analysis at the end of the experiment. (A) PO₂, (B) PCO₂, (C) pH, (D) HCO₃^-. LPS plus thoracotomy caused a decrease in pH and PO₂, and also an increase in PCO₂. These changes were attenuated by treating with 1400 W (n=6 per group). ^*p<0.05 vs. all other groups with vehicle; ^†p<0.05 vs. vehicle for the same group; ^‡p<0.05 vs. control, LPS, and T groups with vehicle; ^§p< 0.05 vs. control, LPS, and LPS+T+P with vehicle.

Fig. 2

Hemodynamic parameters after 2 hr of mechanical ventilation. (A) Mean arterial pressure, (B) cardiac output. There was no significant difference between groups with or without 1400 W (n=6 per group).

Fig. 3

Representative histology findings (hematoxylin and eosin stain, original magnification, ×100). Lungs were removed after two hours of mechanical ventilation. (A) Control, (B) LPS, (C) T, (D) LPS+T, (E) LPS+T+P, and (F) 1400 W+LPS+T. Inflammatory cells including neutrophils were infiltrated in the interstitium of collapsed alveolar walls and the peribronchiolar portion in the LPS+T group (D). The group of iNOS inhibition with 1400 W shows reduced interstitial inflammation and alveolar collapse (F). The other groups show unremarkable histologic changes. Representative histology findings (hematoxylin and eosin stain, original magnification, ×100). Lungs were removed after two hours of mechanical ventilation. (A) control, (B) LPS, (C) T, (D) LPS+T, (E) LPS+T+P, (F) 1400 W+LPS+T. Inflammatory cells including neutrophils were infiltrated in the interstitium of collapsed alveolar walls and peribronchiolar portion in the LPS+T group (D). Group of iNOS inhibition with 1,400 W shows reduced findings of the interstitial inflammation and alveolar collapse (F). The other groups show unremarkable histologic changes.

Fig. 4

Immunostaining for inducible nitric oxide synthase (iNOS) expression (original magnification, ×200). (A) Control, (B) LPS, (C) T, (D) LPS+T, and (E) LPS+T+P. The LPS-treated group shows increased expression for iNOS on the mononuclear cells (B). In the LPS+T group, marked expression for iNOS on the mononuclear cells was present in the thickened interstitial areas (D). Less expression for iNOS was present in the thoracotomy alone (C) and LPS plus thoracotomy with the PEEP group (E).