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Injurious mechanical ventilation affects neuronal activation in ventilated rats

María Elisa Quilez12, Gemma Fuster12, Jesús Villar13, Carlos Flores14, Octavi Martí-Sistac125, Lluís Blanch12 and Josefina López-Aguilar12*

Author Affiliations

1 CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III. C/ Sinesio Delgado 6, Madrid, 28029, Spain

2 Critical Care Center, Corporació Sanitaria Parc Taulí, Institut Universitari, Esfera UAB. Parc Taulí sn. Sabadell, 08208, Spain

3 Research Unit, Hospital Universitario Dr.Negrín. Barranco de la Ballena s/n. Las Palmas de Gran Canaria, 35010, Spain

4 Research Unit, Hospital Universitario N.S. de Candelaria. Carretera del Rosario 145, Santa Cruz de Tenerife, 38010, Spain

5 Universitat Autònoma de Barcelona. Campus de la UAB, Bellaterra, 08193, Spain

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Critical Care 2011, 15:R124  doi:10.1186/cc10230

Published: 13 May 2011



Survivors of critical illness often have significant long-term brain dysfunction, and routine clinical procedures like mechanical ventilation (MV) may affect long-term brain outcome. We aimed to investigate the effect of the increase of tidal volume (Vt) on brain activation in a rat model.


Male Sprague Dawley rats were randomized to three groups: 1) Basal: anesthetized unventilated animals, 2) low Vt (LVt): MV for three hours with Vt 8 ml/kg and zero positive end-expiratory pressure (ZEEP), and 3) high Vt (HVt) MV for three hours with Vt 30 ml/kg and ZEEP. We measured lung mechanics, mean arterial pressure (MAP), arterial blood gases, and plasma and lung levels of cytokines. We used immunohistochemistry to examine c-fos as a marker of neuronal activation. An additional group of spontaneously breathing rats was added to discriminate the effect of surgical procedure and anesthesia in the brain.


After three hours on LVt, PaO2 decreased and PaCO2 increased significantly. MAP and compliance remained stable in MV groups. Systemic and pulmonary inflammation was higher in MV rats than in unventilated rats. Plasma TNFα was significantly higher in HVt than in LVt. Immunopositive cells to c-fos in the retrosplenial cortex and thalamus increased significantly in HVt rats but not in LVt or unventilated rats.


MV promoted brain activation. The intensity of the response was higher in HVt animals, suggesting an iatrogenic effect of MV on the brain. These findings suggest that this novel cross-talking mechanism between the lung and the brain should be explored in patients undergoing MV.