One hallmark of acute lung injury (ALI) is pulmonary edema. Mechanical ventilation of ALI patients with edema tends to over-distend the portions of the lung remaining air filled. The over-distension exacerbates the underlying lung injury and the mortality rate remains above 30%. This proposal aims to test novel methods of reducing ventilator induced lung injury (VILI). Working in the isolated, perfused rat lung preparation, we generate a local edema model by microinfusing albumin solution into subpleural alveoli to elucidate the mechanical effects of heterogeneous liquid-filling or we generate a global, permeability model of edema by including oleic acid in the perfusate. In either model, we image an edematous region by confocal microscopy. We have developed a novel method for determining surface tension in edematous alveoli, enabling in situ assessment of the effect of additives on interfacial surface tension. Using these methods, we will assess the ability of surface tension manipulations and custom-designed ventilation waveforms to protect the edematous lung from VILI.

Public Health Relevance

Acute lung injury patients are treated by mechanical ventilation. However ventilation often causes an over-distension injury of the lung that exacerbates the underlying injury. The mortality rate remains above 30%. This proposal aims to test novel methods of reducing ventilator induced lung injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL113577-01A1
Application #
8439305
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Harabin, Andrea L
Project Start
2013-02-15
Project End
2018-01-31
Budget Start
2013-02-15
Budget End
2014-01-31
Support Year
1
Fiscal Year
2013
Total Cost
$312,216
Indirect Cost
$87,216
Name
Stevens Institute of Technology
Department
Chemistry
Type
Schools of Engineering
DUNS #
064271570
City
Hoboken
State
NJ
Country
United States
Zip Code
07030
Kharge, Angana Banerjee; Wu, You; Perlman, Carrie E (2015) Sulforhodamine B interacts with albumin to lower surface tension and protect against ventilation injury of flooded alveoli. J Appl Physiol (1985) 118:355-64
Wu, You; Kharge, Angana Banerjee; Perlman, Carrie E (2014) Lung ventilation injures areas with discrete alveolar flooding, in a surface tension-dependent fashion. J Appl Physiol (1985) 117:788-96