Time Course of Altered Ventilatory Activity Evoked by Intratracheal Lipopolysaccharide (LPS) Administration in Spontaneously Breathing Adult C57BL/6 Male Mice

Abstract

Intratracheal (IT) administration of LPS, which is often used as model of acute lung injury/acute respiratory distress syndrome in rodents, has been reported to induce time‐dependent changes in expression of pro‐inflammatory cytokines in respiratory‐related medullary regions. Little is known about the time course of alterations in ventilatory activity following IT LPS administration. Therefore, we examined the effects of IT LPS administration (0.5 mg/kg) on ventilatory behavior (recorded using whole body plethysmography) at 2‐, 6‐, 24‐, 48‐, 72‐, 96‐, and 120‐hr in unanesthetized spontaneously breathing adult C57BL/6 male mice. Before LPS, ventilatory activity was characterized by a regular pattern of breathing with spontaneous periodic short duration apneic pauses (as previously described in this strain) and periodic sighs. After LPS, multiple time‐dependent ventilatory behaviors were observed, with the most common patterns consisting of: (1) periods of dysrhythmic breathing characterized by clusters of typically 2‐3 (but as many as 6) breaths of varying magnitude in rapid succession, with each cluster being followed by an apneic pause of varying duration; (2) brief periods of regular stable breathing that exhibited increased frequency at 2‐hr, a return to pre‐LPS levels at 6‐hr, and an increase again at and after 24‐hr, with tidal volumes that were unchanged or reduced, especially at later time points; (3) numerous prolonged apneic pauses; and (4) an increased incidence of sighs. These findings indicate that IT LPS produces time‐dependent modulation of ventilatory activity, which may reflect the LPS‐induced differences in the cytokine expression profile.