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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Respiratory Integrative Biology and Translational Research Study Section (RIBT)
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Harabin, Andrea L
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Stevens Institute of Technology
Biomed Engr/Col Engr/Engr Sta
United States
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Nguyen, Tam L; Perlman, Carrie E (2018) Tracheal acid or surfactant instillation raises alveolar surface tension. J Appl Physiol (1985) :
Wu, You; Nguyen, Tam L; Perlman, Carrie E (2017) Accelerated deflation promotes homogeneous airspace liquid distribution in the edematous lung. J Appl Physiol (1985) 122:739-751
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
Perlman, Carrie E (2014) On modeling edematous alveolar mechanics. J Appl Physiol (1985) 117:937
Kharge, Angana Banerjee; Wu, You; Perlman, Carrie E (2014) Surface tension in situ in flooded alveolus unaltered by albumin. J Appl Physiol (1985) 117:440-51
Perlman, Carrie E; Wu, You (2014) In situ determination of alveolar septal strain, stress and effective Young's modulus: an experimental/computational approach. Am J Physiol Lung Cell Mol Physiol 307:L302-10