Objectives: Here, we investigated the effects of hyperventilation on acute lung injury (ALI) in spontaneously breathing rats. Methods: Wistar rats were randomized to receive either intraperitoneal lipopolysaccharides (LPS) or saline, and intravenous infusion of NH4Cl (to induce metabolic acidosis and hyperventilation) or saline. Four groups were established: control-control (C-C), control-hyperventilation (C-HV), LPS-control (LPS-C), and LPS-hyperventilation (LPS-HV). Venous blood gases were collected before and after NH4Cl infusion and analyzed to confirm the presence of metabolic acidosis and hyperventilation. After euthanasia, lung injury was assessed using the ALI score, morphometric quantification of perivascular edema, neutrophil counts in the bronchoalveolar lavage, and mRNA expression of biological markers in the lung tissue. Results: Hyperventilation induced inflammatory lung injury in previously healthy lungs and exacerbated injuries previously induced by LPS (ALI score: C-C=0.14 [IQR 0.12; 0.14]; C-HV=0.36 [IQR 0.31; 0.37]; LPS-C=0.51 [IQR 0.50; 0.54]; LPS-HV=0.58 [IQR 0.56; 0.62]; p<0.01). Perivascular edema, neutrophil counts in bronchoalveolar lavage, and amphiregulin mRNA expression were higher in the LPS-HV group compared to the control group. Conclusions: Hyperventilation increased inflammatory injury in rats with ALI during spontaneous ventilation. These results suggest that the impact of vigorous spontaneous breathing efforts on worsening inflammatory lung injury warrants further investigation.

Keywords: acute lung injury, acute respiratory distress syndrome, spontaneous breathing, hyperventilation, lung injury.