Pathophysiological profile of non-ventilated lung injury in healthy female pigs undergoing mechanical ventilation

BackgroundLung regions excluded from mechanical insufflation are traditionally assumed to be spared from ventilation-associated lung injury. However, preliminary data showed activation of potential mechanisms of injury within these non-ventilated regions (e.g., hypoperfusion, inflammation).MethodsIn the present study, we hypothesized that non-ventilated lung injury (NVLI) may develop within 24 h of unilateral mechanical ventilation in previously healthy pigs, and we performed extended pathophysiological measures to profile NVLI. We included two experimental groups undergoing exclusion of the left lung from the ventilation with two different tidal volumes (15 vs 7.5 ml/kg) and a control group on bilateral ventilation. Pathophysiological alteration including lung collapse, changes in lung perfusion, lung stress and inflammation were measured. Lung injury was quantified by histological score.ResultsHistological injury score of the non-ventilated lung is significantly higher than normally expanded lung from control animals. The histological score showed lower intermediate values (but still higher than controls) when the tidal volume distending the ventilated lung was reduced by 50%. Main pathophysiological alterations associated with NVLI were: extensive lung collapse; very low pulmonary perfusion; high inspiratory airways pressure; and higher concentrations of acute-phase inflammatory cytokines IL-6, IL-1 beta and TNF-alpha and of Angiopoietin-2 (a marker of endothelial activation) in the broncho-alveolar lavage. Only the last two alterations were mitigated by reducing tidal volume, potentially explaining partial protection.ConclusionsNon-ventilated lung injury develops within 24 h of controlled mechanical ventilation due to multiple pathophysiological alterations, which are only partially prevented by low tidal volume.Respiratory failure that occurs in cases of atelectasis, pneumonia and acute hypoxemic respiratory failure a machine called a mechanical ventilator is used to move air in and out of the patient's lungs. We know that the use of a mechanical ventilator can induce lung injury, but complete exclusion from ventilation might not be safe. Using pig lungs to mimic the patient's lungs, we evaluated the use of a ventilator against non-use. We find that the lungs sustained injury regardless of ventilator use. The non-ventilated lung injury consisted of collapse (lack of expansion), low amount of blood flow, high ventilation pressure and inflammatory response. Physicians should be aware that also the regions of the lung not receiving ventilation are at risk of injury.Spinelli et al. show that non-ventilated lung injury develops within 24 h of unilateral mechanical ventilation in healthy pigs. Pathophysiological alterations included collapse, hypoperfusion, high inspiratory pressure and inflammation and were only partially mitigated by low tidal volume.