Efeitos da hiperventilação espontânea na lesão pulmonar aguda induzida por injeção intraperitoneal de lipopolissacáride em ratos wistar

Abstract

Introduction: Lung injury associated with spontaneous respiratory effort can worsen inflammatory acute lung injury (ALI). Our objective, therefore, was to compare lung injury and injury after a period of hyperventilation caused by intravenous administration of ammonium chloride (NH4Cl) in rats with and without acute lung injury caused by intraperitoneal lipopolysaccharide (LPS). Methods: Wistar rats were randomized into two groups to receive intraperitoneal LPS or saline. After 24 hours, each group was randomized to receive intravenous NH4Cl over 180 minutes, or saline. Four groups were constructed: control-control (C-C), control-hyperventilation (C-HV), LPS-control (LPS-C) and LPS-hyperventilation (LPS-HV). After 180 minutes, venous blood gas analysis was collected to confirm the occurrence of metabolic acidosis and hyperventilation. The animals were euthanized and lung injury was assessed by the LPA score, morphometric quantification of perivascular edema, number of neutrophils in bronchoalveolar lavage (BAL), mRNA expression of biological markers in lung tissue. Results: Hyperventilation induced lung inflammatory injury in previously normal lungs and worsened injury previously caused by LPS (LPA score: C-C=0.14 [IQR 0.12, 0.14]; C-HV=0.36 [IQR 0.31; 0.37]; LPS-C=0.51 [IIQ 0.50; 0.54]; LPS-HV=0.58 [IIQ 0.56; 0.62]; p<0.01). Perivascular edema, BAL neutrophil count, and amphiregulin mRNA expression were higher in the LPS-HV group. Conclusion: Hyperventilation increased lung inflammatory injury in rats with ALI during spontaneous ventilation. These results suggest that we should continue to study the role of vigorous spontaneous efforts in worsening inflammatory lung injury.