Lung
ischemia-reperfusion injury remains a major complication after
lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of
lung injury induced by
endotoxin,
surfactant depletion by saline lavage, and
hydrochloric acid. However, no study has compared the
biological impact of VV vs. VCV in lung
ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1)
ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2)
Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and
Sham groups were further randomized to one of two ventilation strategies: VCV (n = 6/group) [tidal volume (VT) = 6 mL/kg,
positive end-expiratory pressure (PEEP) = 2 cmH2O, fraction of inspired
oxygen (FiO2) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated VT values (n = 1200; mean VT = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood
gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH20/ml and 2.0 ± 0.8 cmH20/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of
interleukin-6 and
intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of
surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung
ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.