Abstract
Emphysema is characterized by loss of lung tissue elasticity and destruction of structures supporting alveoli and capillaries. The impact of mechanical ventilation strategies on ventilator-induced lung injury (VILI) in emphysema is poorly defined. New ventilator strategies should be developed to minimize VILI in emphysema. The present study was divided into two protocols: (1) characterization of an elastase-induced emphysema model in rats and identification of the time point of greatest cardiorespiratory impairment, defined as a high specific lung elastance associated with large right ventricular end-diastolic area; and (2) comparison between variable (VV) and conventional volume-controlled ventilation (VCV) on lung mechanics and morphometry, biological markers, and cardiac function at that time point. In the first protocol, Wistar rats (n = 62) received saline (SAL) or porcine pancreatic elastase (ELA) intratracheally once weekly for 4 weeks, respectively. Evaluations were performed 1, 3, 5, or 8 weeks after the last intratracheal instillation of saline or elastase. After identifying the time point of greatest cardiorespiratory impairment, an additional 32 Wistar rats were randomized into the SAL and ELA groups and then ventilated with VV or VCV (n = 8/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O, fraction of inspired oxygen (FiO2) = 0.4] for 2 h. VV was applied on a breath-to-breath basis as a sequence of randomly generated VT values (mean VT = 6 mL/kg), with a 30% coefficient of variation. Non-ventilated (NV) SAL and ELA animals were used for molecular biology analysis. The time point of greatest cardiorespiratory impairment, was observed 5 weeks after the last elastase instillation. At this time point, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC)-1, amphiregulin, angiopoietin (Ang)-2, and vascular endothelial growth factor (VEGF) mRNA levels were higher in ELA compared to SAL. In ELA animals, VV reduced respiratory system elastance, alveolar collapse, and hyperinflation compared to VCV, without significant differences in gas exchange, but increased right ventricular diastolic area. Interleukin-6 mRNA expression was higher in VCV and VV than NV, while surfactant protein-D was increased in VV compared to NV. In conclusion, VV improved lung function and morphology and reduced VILI, but impaired right cardiac function in this model of elastase induced-emphysema.
Highlights
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation due to an enhanced chronic inflammatory response (GOLD, 20151), and can lead to respiratory failure and the need for ventilator support (MacIntyre and Huang, 2008)
The present study was divided into two protocols: (1) characterization of an elastase-induced emphysema model in rats, with identification of the time point of greatest cardiorespiratory impairment, defined as a high specific lung elastance associated with large right ventricular end-diastolic area; and (2) comparison, at that time point, of the effects of Variable ventilation (VV) vs. VCV on gas exchange, lung mechanics and histology, right ventricular function, biological markers associated with inflammation, damage inflicted to alveolar epithelial and endothelial cells, and alveolar stretch
Fifty-six rats were used to evaluate lung mechanics and morphometry, end-expiratory lung volume (EELV), biological markers associated with inflammation, alveolar stretch, type II epithelial cell mechanotransduction, and endothelial cell damage, as well as echocardiographic parameters (n = 7 at each time point in SAL and ELA groups)
Summary
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation due to an enhanced chronic inflammatory response (GOLD, 20151), and can lead to respiratory failure and the need for ventilator support (MacIntyre and Huang, 2008). In patients with COPD, invasive volume-controlled (VCV) or pressurecontrolled mechanical ventilation may exacerbate preexisting lung damage as a result of time-constant inhomogeneity, which predisposes to delayed inflation of some lung areas and overdistension of other regions (Laghi et al, 2001; MacIntyre and Huang, 2008); this, in turn, may lead to ventilator-induced lung injury (VILI) and a negative impact on right ventricular function (Vieillard-Baron et al, 1999; Wrobel et al, 2015). VV promotes lung functional benefits in experimental acute respiratory distress syndrome (ARDS) (Spieth et al, 2009b; Ruth Graham et al, 2011), severe bronchospasm (Mutch et al, 2007), and prolonged anesthesia (Mutch et al, 2000)
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