ABSTRACT
BACKGROUND: Ventilatory strategy and specifically positive end-expiratory pressure (PEEP) can modulate the inflammatory response and pulmonary-to-systemic translocation of lipopolysaccharide (LPS). Both inflammation and ventilatory pattern may modify brain activation, possibly worsening the patient's outcome and resulting in cognitive sequelae. METHODS: We prospectively studied Sprague-Dawley rats randomly assigned to undergo 3âh mechanical ventilation with 7âmL/kg tidal ventilation and either 2âcmH2O or 7âcmH2O PEEP after intratracheal instillation of LPS or saline. Healthy nonventilated rats served as baseline. We analyzed lung mechanics, gas exchange, lung and plasma cytokine levels, lung apoptotic cells, and lung neutrophil infiltration. To evaluate brain neuronal activation, we counted c-Fos immunopositive cells in the retrosplenial cortex (RS), thalamus, supraoptic nucleus (SON), nucleus of the solitary tract (NTS), paraventricular nucleus (PVN), and central amygdala (CeA). RESULTS: LPS increased lung neutrophilic infiltration, lung and systemic MCP-1 levels, and neuronal activation in the CeA and NTS. LPS-instilled rats receiving 7âcmH2O PEEP had less lung and systemic inflammation and more c-Fos-immunopositive cells in the RS, SON, and thalamus than those receiving 2âcmH2O PEEP. Applying 7âcmH2O PEEP increased neuronal activation in the CeA and NTS in saline-instilled rats, but not in LPS-instilled rats. CONCLUSIONS: Moderate PEEP prevented lung and systemic inflammation secondary to intratracheal LPS instillation. PEEP also modified the neuronal activation pattern in the RS, SON, and thalamus. The relevance of these differential brain c-Fos expression patterns in neurocognitive outcomes should be explored.
