Positive pressure ventilation exerts an increased stress and strain in the presence of pulmonary fibrosis. Thus, ventilation strategies that avoid high pressures while maintaining lung aeration are of paramount importance. Although physiologically variable ventilation (PVV) has proven beneficial in various models of pulmonary disease, its potential advantages in pulmonary fibrosis have not been investigated. Therefore, we assessed the benefit of PVV over conventional pressure-controlled ventilation (PCV) in a model of pulmonary fibrosis. Lung fibrosis was induced with intratracheal bleomycin in rabbits. Fifty days later, the animals were randomized to receive 6 h of either PCV (n = 10) or PVV (n = 11). The PVV pattern was prerecorded in spontaneously breathing, healthy rabbits. Respiratory mechanics and gas exchange were assessed hourly; end-expiratory lung volume and intrapulmonary shunt fraction were measured at hours 0 and 6. Histological and cellular analyses were performed. Fifty days after bleomycin treatment, the rabbits presented elevated specific airway resistance [69 ± 26% (mean ± 95% confidence interval)], specific tissue damping (38 ± 15%), and specific elastance (47 ± 16%) along with histological evidence of fibrosis. Six hours of PCV led to increased respiratory airway resistance (Raw, 111 ± 30%), tissue damping (G, 36 ± 13%) and elastance (H, 58 ± 14%), and decreased end-expiratory lung volume (EELV, -26 ± 7%) and oxygenation ([Formula: see text]/[Formula: see text], -14 ± 5%). The time-matched changes in the PVV group were significantly lower for G (22 ± 9%), H (41 ± 6%), EELV (-13 ± 6%), and [Formula: see text]/[Formula: see text] ratio (-3 ± 5%, P < 0.05 for all). There was no difference in histopathology between the ventilation modes. Thus, prolonged application of PVV prevented the deterioration of gas exchange by reducing atelectasis development in bleomycin-induced lung fibrosis.

NEW & NOTEWORTHY The superposition of physiological breathing variability onto a conventional pressure signal during prolonged mechanical ventilation prevents atelectasis development in bleomycin-induced lung fibrosis. This advantage is evidenced by reduced deterioration in tissue mechanics, end-expiratory lung volume, ventilation homogeneity, and gas exchange.