Brainstem Inflammation Modulates The Ventilatory Pattern And Its Variability After Acute Lung Injury In Rodents

Acute lung injury (ALI) increases respiratory rate (fR) and ventilatory pattern predictability (VPV), but also evokes peripheral and central inflammation. We hypothesized that central inflammation has a role in determining the ventilatory pattern after ALI. In rat pups, we intratracheally injected either bleomycin to induce ALI or saline as a sham control. One week later, we recorded the ventilatory pattern of the rat pups using flow-through plethysmography, then formed in situ preparations from these pups and recorded their 'fictive' patterns from respiratory motor nerves. Compared to the ventilatory pattern of the sham rat pups, injured rat pups had increased fR and predictability. Surprisingly, the fictive patterns of the in situ preparations from ALI pups retained these characteristics despite removing their lungs to eliminate pulmonary sensory inputs and perfusing them with hyperoxic artificial cerebral spinal fluid to minimize peripheral chemoreceptor input. Histologic processing revealed increased immunoreactivity of the proinflammatory cytokine Interleukin-1β (IL-1β) in the nucleus tractus solitarii (nTS) from ALI but not sham rats. In subsequent experiments, we microinjected IL-1β in the nTS bilaterally in anesthetized naïve adult rats, which increased fR and predictability of VPV after 2h. Finally, we infused indomethacin intracerebroventricularly during the week of survival after ALI. This did not affect sham rats, but mitigated changes in fR and VPV in ALI rats. We conclude that neuro-inflammation has an essential role in determining the ventilatory pattern of ALI rats. This article is protected by copyright. All rights reserved.