Inflammatory consequences of lung ischemia-reperfusion injury and low-pressure ventilation

Lung ischemia-reperfusion injury (LIRI) is a clinical problem observed during thoracic surgery, and adversely affects patient recovery. A better understanding of the mechanisms of LIRI could be helpful to develop new therapeutic strategies. The objective was to assess the inflammatory and apoptotic consequences of LIRI using an in vivo rat model.

The left lung of Sprague-Dawley rats was subjected to ischemia for 120 min and reperfusion for up to 4 h. Ventilated controls underwent sham surgery and low-pressure mechanical ventilation for the above mentioned time points. Lung tissue was analyzed for histopathology and for the expression of inflammatory and apoptotic mediators.

Low-pressure ventilated controls showed a clear increase in myeloperoxidase activity, macrophage inflammatory protein-2, interleukin-6, and caspase-3 expression compared with naïve animals. However, LIRI animals showed faster kinetics of pulmonal myeloperoxidase activity and caspase-3 expression. Moreover, only LIRI animals showed increased inducible nitric oxide synthase and interleukin-6 expression and had a decreased interleukin-10 expression in the lung compared to ventilated controls. Furthermore, lungs of LIRI animals contained much more cellular infiltrates compared with ventilated controls.

Low-pressure mechanical ventilation induces an inflammatory response in the lung, but LIRI accelerates the kinetics of granulocyte infiltration and apoptosis. Moreover, LIRI skews the cytokine balance to a pro-inflammatory profile. Finally, LIRI deteriorates lung histology much more than ventilation only.