The goal of this project is to identify promising low-volume ventilation waveforms that will open occluded pulmonary airways with minimal damage to sensitive epithelial tissue. This problem is physiologically significant because the obstruction of pulmonary airways by a viscous liquid occlusion occurs in a variety of diseases including respiratory distress syndrome (RDS), acute respiratory distress syndrome (ARDS) and asthma. Airway closure contributes to mortality through ventilation-perfusion mismatch from reduced gas transport. In RDS and potentially ARDS, the lining fluid surface tension is elevated due to surfactant deficiency, which increases the pressure necessary to open the occluded airways. The proposed studies will test the hypothesis that pulsatile ventilation waveforms can be used to minimize damage to airway epithelial cells by maximizing surfactant transport and optimizing biophysical responses to reduce the damaging mechanical stress imparted on airway epithelium.
Each specific aim couples computational simulations to laboratory experiments to elucidate the interactions between mechanical stresses, transport properties, surfactant biophysical responses and cell damage during the migration of a finger of air through a cylindrical tube as the model system.
The specific aims of the project are:
Specific Aim #1 : Test the prediction that epithelial cells are wounded by the transient pressure gradient that sweeps across the cells during airway reopening and determine the stimulus/response behavior for steady and pulsatile flows.
Specific Aim #2 : Investigate the prediction that surfactant biophysical properties coupled to interfacial flow waveforms can protect the epithelium, and use the principles derived from these studies to predict properties of ventilation waveforms that will recruit an obstructed airway with minimal damage to the airway epithelium. Successful completion of this project will lead to improved understanding of the role of ventilation on lung injury. Improved ventilation protocols resulting from the principles derived from this study could lead to reduced mortality of infants and adults suffering from respiratory distress syndrome or asthma. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL081266-02
Application #
7211390
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Harabin, Andrea L
Project Start
2006-06-01
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
2
Fiscal Year
2007
Total Cost
$346,345
Indirect Cost
Name
Tulane University
Department
Biomedical Engineering
Type
Schools of Arts and Sciences
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Yamaguchi, Eiichiro; Giannetti, Matthew J; Van Houten, Matthew J et al. (2014) The unusual symmetric reopening effect induced by pulmonary surfactant. J Appl Physiol (1985) 116:635-44
Fujioka, Hideki; Halpern, David; Gaver 3rd, Donald P (2013) A model of surfactant-induced surface tension effects on the parenchymal tethering of pulmonary airways. J Biomech 46:319-28
Halpern, David; Gaver 3rd, Donald P (2012) The influence of surfactant on the propagation of a semi-infinite bubble through a liquid-filled compliant channel. J Fluid Mech 698:125-159
Glindmeyer 4th, Henry W; Smith, Bradford J; Gaver 3rd, Donald P (2012) In situ enhancement of pulmonary surfactant function using temporary flow reversal. J Appl Physiol 112:149-58
Jacob, Anne-Marie; Gaver 3rd, Donald P (2012) Atelectrauma disrupts pulmonary epithelial barrier integrity and alters the distribution of tight junction proteins ZO-1 and claudin 4. J Appl Physiol 113:1377-87
Smith, Bradford J; Lukens, Sarah; Yamaguchi, Eiichiro et al. (2011) Lagrangian transport properties of pulmonary interfacial flows. J Fluid Mech 705:234-257
Smith, B J; Yamaguchi, E; Gaver 3rd, D P (2010) A translating stage system for ýý-PIV measurements surrounding the tip of a migrating semi-infinite bubble. Meas Sci Technol 21:
Pillert, Jerina E; Gaver 3rd, Donald P (2009) Physicochemical effects enhance surfactant transport in pulsatile motion of a semi-infinite bubble. Biophys J 96:312-27
Williams, Harvey A R; Fauci, Lisa J; Gaver 3rd, Donald P (2009) EVALUATION OF INTERFACIAL FLUID DYNAMICAL STRESSES USING THE IMMERSED BOUNDARY METHOD. Discrete Continuous Dyn Syst Ser B 11:519-540
Yamaguchi, Eiichiro; Smith, Bradford J; Gaver 3rd, Donald P (2009) ýý-PIV measurements of the ensemble flow fields surrounding a migrating semi-infinite bubble. Exp Fluids 47:309-320

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