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P188 HIGH TIDAL VOLUME VENTILATION INDUCES RECRUITMENT OF ACTIVATED LEUCOCYTES TO EXTRAPULMONARY ORGANS IN AN IN-VIVO MOUSE MODEL
AC Waite, MR Wilson, M Takata. Department of Anaesthetics, Pain Medicine and Intensive Care, Imperial College, London, UK
Background: Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) have a high mortality of up to 50%. The most effective supportive therapy is mechanical ventilation but this can exacerbate underlying lung injury, a phenomenon known as ventilator-induced lung injury (VILI). The majority of patients with ARDS die from multiple system organ failure (MSOF) rather than respiratory failure, but the mechanisms are poorly understood and the role of ventilation in this is unclear. Neutrophils and inflammatory Gr-1high monocytes play an important role in the pathogenesis of lung dysfunction in VILI and ALI. However, the role of leucocytes in the dysfunction of other organs during VILI is largely unknown. Our objective was to investigate whether leucocytes were activated and recruited to non-pulmonary organs due to injurious mechanical ventilation.
Methods: Anaesthetised C57BL6 mice were ventilated for 2 h with low (7–9 ml//kg) or high (33–37 ml/kg) tidal volume (VT) ventilation. Flow cytometric analysis of cell suspensions from liver, kidney and blood samples was undertaken to quantify neutrophils, Gr-1high and Gr-1low monocytes in each tissue, and assess cellular activation in terms of surface l-selectin and CD11b expression.
Results: High VT ventilation resulted in recruitment of both neutrophils and Gr-1high monocytes to the liver (see fig) compared with low VT ventilation. In addition, liver-recruited neutrophils had significantly higher surface CD11b expression, indicative of greater activation (p<0.05). There was a trend for Gr-1high monocytes to marginate to the kidney with high VT, whereas neutrophil numbers were increased in the blood with high VT ventilation (p<0.05 vs low VT).
Conclusion: These results demonstrate for the first time that pure high VT ventilation …
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