Intratracheal Lipopolysaccharide (LPS) Administration Attenuates Acute Hypoxic Ventilatory Response (HVR) in Spontaneously Breathing Adult C57BL/6 Male Mice

Abstract

Intratracheal (IT) administration of lipopolysaccharide (LPS) not only produces acute lung injury but also induces time‐dependent changes in expression of pro‐inflammatory cytokines in respiratory‐related brainstem regions. The influence of IT LPS on control of breathing, including the acute hypoxic ventilatory response (HVR), has received little attention. Therefore, we examined the effects of IT LPS administration (0.5 mg/kg) at 2‐, 6‐, and 24‐hr post‐LPS on the HVR (10% O2 for 60‐90 s; recorded using whole body plethysmography) and recovery from acute hypoxia in unanesthetized spontaneously breathing adult C57BL/6 male mice. Before LPS, the HVR was characterized by a robust increase in breathing frequency (fb) and tidal volume (VT). IT LPS not only altered the basal breathing pattern but also markedly blunted the hypoxia‐induced increase in fb and produced a slight attenuation of the increase in VT. Specifically, the hypoxia‐induced increase in fb was reduced from a range of 100‐178% increase pre‐LPS to 21‐36% increase post‐LPS; the hypoxia‐induced increase in VT was reduced from a range of 135‐177% increase pre‐LPS to 100‐140% increase post‐LPS. The effect on fb was greatest at 6‐hr post‐LPS while that on VT was greatest at 24‐hr post‐LPS. During recovery from hypoxia, before LPS, there was an increase in the incidence of sighs and spontaneous apneic pauses; however, after LPS, these behaviors were also attenuated. These findings indicate that IT LPS alters the acute HVR and its recovery in a time‐dependent manner, with a dominant effect being related to frequency modulation.