Abstract
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.
Highlights
Ischemia-reperfusion (IR) injury remains a major problem after lung transplantation, and may result in severe lung damage with development of the acute respiratory distress syndrome in donor lungs or primary graft dysfunction in lung transplant recipients (Christie et al, 2005) Lung damage occurs early in the ischemic period, but is exacerbated during reperfusion (de Perrot et al, 2003)
Variable ventilation mimics the physiological fluctuation of tidal volume observed in resting subjects (Tobin et al, 1988; Frey et al, 1998), and compared to conventional protective, but non-variable mechanical ventilation, has been associated with better lung mechanics (Gama de Abreu et al, 2008; Spieth et al, 2009), reduced lung damage (Spieth et al, 2009; Kiss et al, 2016; Samary et al, 2016), and, better mechanotransduction at the alveolar-capillary membrane level in experimental lung injury induced by surfactant depletion through saline lavage (Spieth et al, 2009), acid aspiration (Ma et al, 2011), and endotoxin (Samary et al, 2016)
To date, no study has compared the biological impact of variable ventilation (VV) vs. conventional protective volume-controlled ventilation (VCV) mode in ARDS induced by lung ischemiareperfusion
Summary
Ischemia-reperfusion (IR) injury remains a major problem after lung transplantation, and may result in severe lung damage with development of the acute respiratory distress syndrome in donor lungs or primary graft dysfunction in lung transplant recipients (Christie et al, 2005) Lung damage occurs early in the ischemic period, but is exacerbated during reperfusion (de Perrot et al, 2003). The anoxic condition, combined with a lack of mechanotransduction in the arterioles and capillaries (Lansman, 1988), induces dysfunction of endothelial and epithelial cells and other immune cells, as well as activation of nuclear factor-κB-derived cytokines (Ishiyama et al, 2005) These changes translate into increased pulmonary vascular resistance and alveolar edema, which impair lung function (Jurmann et al, 1990). Lung ischemia-reperfusion (IR) injury is a complex phenomenon involving intracellular injury processes, and injurious inflammatory responses and biochemical changes; the pathophysiology of lung injury due to IR is different from that of the aforementioned ARDS models (den Hengst et al, 2010; Matute-Bello et al, 2011) Within this context, we hypothesized that VV might reduce early pulmonary inflammation and alveolar endothelial cell and type II epithelial cell injury, improving respiratory system mechanics and reducing lung damage. We designed the present study to evaluate the effects of VV vs. VCV on lung function and histology, biological markers associated with inflammation, and damage inflicted to alveolar epithelial and endothelial cells in a rat model of lung ischemia-reperfusion injury
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