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A2335 - Assessment of Ventilator Induced Lung Injury in an Animal Model of Pulmonary Fibrosis
Author Block: C. Ortiz, N. Hoftman, M. Vaillancourt, M. Weksler, N. Cao, T. Le, M. Eghbali, A. Mahajan, S. Umar; Anesthesiology, UCLA, Los Angeles, CA, United States.
Rationale: The gold standard formula for tidal volume (VT) selection during surgery, 6-8 ml/kg predicted body weight (PBW), aims to mitigate ventilator-induced lung injury (VILI) by reducing mechanical forces transmitted to alveoli. Our recent work has shown, however, that PBW correlates poorly with lung volumes, especially in patients with severely reduced compliance. Pulmonary fibrosis (PF) patients may be particularly at risk for barotrauma despite current lung-protective ventilation strategies. Pulmonary-focused metrics, specifically forced vital capacity, may be used to calculate individualized tidal volume, which could reduce VILI. We aimed to further examine the susceptibility of fibrotic lungs to VILI in an established animal model of PF. We hypothesize that rats with PF have decreased lung compliance and are more susceptible to VILI. Methods: Adult male Wistar rats received intratracheal bleomycin at 2.5 mg/kg and maintained for 3 weeks. CT scan was performed under isoflurane anesthesia, while spontaneously ventilating. Analysis of lung tissue from bleomycin-treated rats (n=7) and lung tissue from human patients with advanced idiopathic pulmonary fibrosis (n=5) was performed. For mechanical ventilation experiment, anesthetized and paralyzed animals were tracheotomized and ventilated using low VT (4cc/kg, n=3) or high VT (15 cc/kg, n=3). Airway pressures and lung compliance were recorded. Blood and bronchoalveolar lavage samples were collected. Lungs were fixed for Trichrome staining. Results: Bleomycin treated animals developed significant PF, as seen on CT imaging and histology. Analysis of lung tissue from bleomycin-treated rats and lung tissue from human patients with advanced idiopathic PF found a comparable extent of fibrosis as quantified by the Ashcroft score (mean score 4 in rats, 6 in humans), and by inflammatory changes including macrophage infiltration, suggesting that the lung pathology induced by bleomycin treatment in rats is similar to that seen in human IPF, making our model a strong platform for translational studies. In PF rats, larger VT resulted in significantly higher alveolar plateau pressures during mechanical ventilation. Histologic evidence of lung injury and inflammation was more extensive in PF animals exposed to high VT than those exposed to low VT. Conclusions: These data support the validity of bleomycin exposure as a clinically relevant model of PF. Fibrotic lungs appear to develop more lung injury and inflammation when exposed to higher tidal volumes. CT imaging reveals fibrotic changes and can potentially be used for 3D reconstruction and estimation of lung volumes. Future work will focus on developing more protective ventilatory strategies for fibrotic lungs.