This proposal intends to study two aspects of pulmonary transport, one in the gas phase and one in the airway liquid phase, which are involved in respiratory therapeutic modalities. The distribution of transported material (gas, surfactant, drugs) in both depends upon the interaction of diffusive and convective processes as well as boundary conditions determined by common local lung structure and composition, while techniques to investigate both involve tracking the dispersion of an imposed gas or surfactant bolus or microbolus. Our major objective is to identify the important determinants of contaminant transport within the airstream (on the scale of the entire airway tree), and within the airway liquid lining/tissue (on the scale of spreading surfactant). Two important and different studies of transport are proposed which share many similarities both in detail and in approach. In the first project pulmonary gas transport during intra-tracheal insufflation (ITI), with or without external chest vibrations, will be studied to investigate ITI as a means of enhancing C02 removal and ventilatory efficiency in models of chronic ventilatory failure (e.g. spinal cord injury, neuromuscular disorders). The experimental technique underlying this transport study will be to follow the dispersion of a localized bolus of tracer-gas by intra-lumenal gas sampling, in animal and hardware models of ITI. This new technique will allow us to interpret a local D-eff from the concentration data measured at the point of injection, giving us the unique ability to examine regional and local differences in transport. Predictive models of this transport will be developed in tandem with the experimentation to provide a framework for interpreting data and guiding experimental parameter ranges. In the second project pulmonary liquid transport following the delivery of exogenous surfactants, either in aerosol droplets or large scale slugs which feed a surfactant monolayer, will be studied. This situation is found in surfactant replacement therapy for surfactant-deficient neonates or intra-airway drug delivery.
The aim i s to understand how far and how fast the surfactant (plus any dissolved species) is transported from where it impacts on the lining to its destination. The technique underlying this investigation will be the introduction of a localized surfactant bolus (microdroplet or slug) onto the air-liquid interface in animal and hardware models, while video-microscopy and laser interferometric methods will be used to track its dispersion along the interface and to investigate film rupture phenomena. In addition to measuring the spreading rates, use of our theoretical modelling will allow us to infer physical properties of the liquid lining (thickness, viscosity, surface tension) in airways and in alveoli. Theoretical modelling will provide a basis for interpreting the data and suggesting how to control the delivery.
| Levy, Rachel; Hill, David B; Forest, M Gregory et al. (2014) Pulmonary fluid flow challenges for experimental and mathematical modeling. Integr Comp Biol 54:985-1000 |
| Zheng, Y; Fujioka, H; Grotberg, J C et al. (2006) Effects of inertia and gravity on liquid plug splitting at a bifurcation. J Biomech Eng 128:707-16 |
| Zheng, Y; Anderson, J C; Suresh, V et al. (2005) Effect of gravity on liquid plug transport through an airway bifurcation model. J Biomech Eng 127:798-806 |
| Anderson, Joseph C; Molthen, Robert C; Dawson, Christopher A et al. (2004) Effect of ventilation rate on instilled surfactant distribution in the pulmonary airways of rats. J Appl Physiol 97:45-56 |
| Halpern, D; Bull, J L; Grotberg, J B (2004) The effect of airway wall motion on surfactant delivery. J Biomech Eng 126:410-9 |
| Fujioka, Hideki; Grotberg, James B (2004) Steady propagation of a liquid plug in a two-dimensional channel. J Biomech Eng 126:567-77 |
| Grotberg, J B (2001) Respiratory fluid mechanics and transport processes. Annu Rev Biomed Eng 3:421-57 |
| Cassidy, K J; Gavriely, N; Grotberg, J B (2001) Liquid plug flow in straight and bifurcating tubes. J Biomech Eng 123:580-9 |
| Cassidy, K J; Bull, J L; Glucksberg, M R et al. (2001) A rat lung model of instilled liquid transport in the pulmonary airways. J Appl Physiol 90:1955-67 |
| Bull, J L; Nelson, L K; Walsh Jr, J T et al. (1999) Surfactant-spreading and surface-compression disturbance on a thin viscous film. J Biomech Eng 121:89-98 |
Showing the most recent 10 out of 26 publications
