Time‐dependent Characterization of Respiratory Parameters post Bleomycin‐induced Lung Injury

Abstract

Background‐Acute lung injury (ALI) induces inflammation that disrupts the normal alveolar‐capillary endothelial barrier which impairs gas exchange to induces hypoxemia that reflexively increases respiration. Increased respiratory rate (RR) usually develops within a few hours to a few days after ALI. The bleomycin (Bleo)‐induced lung injury rat model has been one of the most widely used animal models to study the mechanisms of respiratory failure post ALI. However, systemic and time‐dependent characterization of respiratory parameters in this model has not been done. In the current study, we aimed to use the plethysmography (DSI system) to characterize the changes in variable respiratory parameters at different stages of lung injury in the bleomycin‐induced ALI rat model.Methods and Results‐ALI was induced in male SD rats (200‐250g) using a single intra‐tracheal injection of Bleo (day 0) and respiratory variables‐ Respiratory rate (RR), Tidal Volume (TV), Minute Ventilation (MV), enhanced pause (Penh), pause (PAU), ratio rate of achieving peak expiatory flow (Rpef), peak inspiratory flow (box) (PIFb), peak expiratory flow box (PEFb), inspiratory time (Ti), expiratory time (Te), expiratory flow at the point of 50%TV (EF50), end inspiratory pause (EIP), end expiratory pause (EEP), relaxation time (Tr) and time of brake (TB) were measured at room air for one hour weekly from W1 (acute phase of ALI) to W4 (recovery phase of ALI) using whole‐ body plethysmography (WBP). Our data showed that MV and RR were significantly elevated from baseline (W0) to W1‐W4 in Bleo‐treated rats whereas TV was decreased from baseline to W1‐W3 post Bleo (p≤0.01 compared to W0). Associated with increased RR, Ti, Te and Tr were significantly shorter at W1‐W4 post Bleo compared to baseline (W0). Penh and Rpef, measures of airway obstruction, were significantly increased at W2 and W1‐W4 post Bleo, respectively. PIFb and PEFb were significantly increased whereas EIP and EEP were significantly decreased in W1‐W4 post Bleo. EF50, a measurement of exhalation flow rate, was significantly increased at W1‐W4 post Bleo.Conclusions‐These data suggest that a single intratracheal instillation of Bleo induced long‐lasting changes in respiratory function from acute to recovery phase of lung injury. Although blood gas returned to the normal level at W4 post Bleo, many respiratory parameters remained abnormal, indicating that pulmonary function might require a longer time to recover in this model.