Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice

Abstract

Introduction Mechanical ventilation (MV) may cause ventilatorinduced lung injury (VILI). Present models of VILI use exceptionally large tidal volumes, causing gross lung injury and haemodynamic shock. In addition, animals are ventilated for a relative short period of time and only after a 'priming' pulmonary insult. Finally, it is uncertain whether metabolic acidosis, which frequently develops in models of VILI, should be prevented. To study VILI in healthy mice, the authors used a MV model with clinically relevant ventilator settings, avoiding massive damage of lung structures and shock, and preventing metabolic acidosis.

Ventilator-Induced Lung Injury: Mechanisms and Future Therapeutic Interventions

“…Notably, Determann et al showed mechanical ventilation with lower tidal volumes also to attenuate development of lung injury in patients without ALI at the onset of mechanical ventilation (Determann et al, 2010). Recent research however, provided striking evidence that even "lung-protective" ventilator settings may result in the development of important aspects of VILI (Cobelens et al, 2009;Vaneker et al, 2007;Wolthuis et al, 2009b). We confirmed these prior reports in a murine model of VILI.…”

“…In an attempt to better reflect the human situation, we used clinically more relevant ventilator settings in our animal studies (Hegeman et al, 2010). In this way, we were able to prevent shock, metabolic acidosis and substantial damage to lung architecture commonly associated with high tidal volumes and/or inspiratory pressures (Wolthuis et al, 2009b). However, even in our relatively mild model of VILI, mechanical ventilation with either low (LV T ) or high tidal volumes (HV T ) caused increased cytokine, chemokine and adhesion molecule expression compared to non-ventilated control (NVC) animals, which was accompanied by marked granulocyte infiltration (Hegeman et al, 2011b).…”

Early Effect of Tidal Volume on Lung Injury Biomarkers in Surgical Patients With Healthy Lungs

“…These patients did not differ from the rest of the group in physiology parameters or other biomarkers. Low V T ventilation attenuates the increases in the concentration of other biomarkers (cytokines, CC16 and procoagulants) [58][59][60][61][62] . However, the interpretation of the increased variability of EBC nitrite or nitrate as an early sign of individual susceptibility to ventilator-induced lung injury deserves caution.…”

Pediatric acute respiratory distress syndrome

“…İyatrojenik akciğer hasarının oluşum mekanizması tam olarak bilinmemekle birlikte, hayvanlar üzerinde yapılan çalışmalar bu konuda yol gösterici olmuştur (13) . Volum travması, yineleyen alveoler açılma-kapanma, oksijen toksisitesi ve biotravma gibi mekanizmaların mekanik ventilasyona bağlı akciğer hasarının başlıca nedenleri olduğu düşünülmektedir.…”