Expiratory time constant heterogeneity in experimental acute respiratory distress syndrome

Purpose This thesis evaluated regional heterogeneity of pulmonary mechanical values within models of lung injury. To this end four separate studies were completed. I evaluated regional expiratory time constant (τE) heterogeneity and tissue strain (ε) in a lung model using functional respiratory imaging (FRI) (Study 1, Chapter 2), and developed an in vivo porcine model of lung injury (Study 2, Chapter 3). This model was used to assess changes in τE due to manipulations of respiratory gas density (Study 3, Chapter 4) and mechanical ventilation parameters (Study 4, Chapter 5). Methods Study 1: Using computerized tomography (CT) images we generated 3-dimensional lung models. These were used calculated global and regional values for resistance, elastance, ε and τE under three different airway pressure conditions. Study 2: Experimental lung injury was induced in 11female Yorkshire X pigs. Necropsy, light and electron microscopy of lung was performed. Study 3: I utilized a multi-compartment model to describe the effects of changes in tidal volume (VT) and positive end-expiratory pressure (PEEP) on lung emptying during passive deflation before and after experimental lung injury in 6 adult female Yorkshire X pigs. Expiratory time constants (τE) were determined by partitioning the expiratory flow-volume (V˙ V) curve into multiple discrete segments. Study 4: Tracheal pressure and flow were measured in 7 pigs before and after experimental lung injury. Gas density was altered by using helium-oxygen (He), sulfur hexafluoride-oxygen (SF6) and nitrogen-oxygen (N2) gas. Conclusions Functional respiratory imaging demonstrates regional variation in both ε and τE. These findings raise questions about the use of whole lung measures of ε and τE to guide clinical management of lung injury (Study 1). I developed a stable model of lung injury using SPA that replicates the light and electron microscopic findings seen in human ARDS (Study 2). A pragmatic strategy using changes in the pattern of expiration described by a multi-compartment model of τE reveals that alterations in and gas density (Study 3) as well as PEEP and VT (Study 4) change expiratory pulmonary mechanics. These observations lay the groundwork for future clinical studies in lung injured patients.Education, Faculty ofKinesiology, School ofGraduat