The candidate has a background in engineering whose goal is to used those skills to help solve clinical problems in an academic critical care environment. The broad, long term objective is to develop improved strategies of mechanical ventilation in the acute respiratory distress syndrome (ARDS) to maximize gas exchange and minimize further lung injury. The hypotheses are: 1) the process of alveolar recruitment depends on the transmission of an air-liquid interface down the airway to the alveoli and therefore, for the same peak pressure, a sustained inflation will recruit more than tidal breaths, 2A) the population of opening and closing pressures can be uniquely determined from a mathematical model of the lung quasi-static pressure-volume (PV) curve, 2B) nitric oxide gas uptake kinetics, because of its rapid reaction time with hemoglobin, should not be significantly affected by pulmonary capillary blood volume and therefore should track changes in alveolar recruitment, and 3) ARDS is a heterogeneous syndrome, therefore, global measurements of recruitment may not correspond to local measurements of recruitment.
The specific aims are: 1) to define the parameters of an effective sustained inflation recruitment maneuver and compare this maneuver to a PEEP increase alone, 2) to determine the correlation between changes in NO uptake kinetics and the predicted population of opened alveoli derived from the PV curve in the mechanically ventilated ARDS lung, and 3) to compare the global measurements of recruitment, such as ARDS lung, and 3) to compare the global measurements of recruitment, such as lung mechanics and NO uptake kinetics, with local measurements using positron emission tomography (PET) including regional gas trapping, atelectasis and shunt. The health relatedness of the project is in its potential to provide tools and knowledge for clinicians to understand the role of alveolar recruitment in ARDS and begin to answer the question of the relative importance of recruitment versus low tidal volumes in protecting the lung from further injury. The research design and methods utilize both animal experiments and clinical studies for each of the three specific aims. Recruitment will be assessed by distributions of opening or closing pressures from the PV curve, NO uptake kinetics, oxygenation, and helium dilution lung volume. For SA1, different sustained inflation maneuvers will be tested in lung lavage-injured sheep to identify the characteristics of a maneuver that will become the standard for the subsequent protocols. Clinical studies will compare the successful maneuvers from the animal experiments to PEEP increases alone. SA2 will compare the time course of derecruitment depending on the PEEP level set according to alveolar closing pressure distributions from the subject's PV curve in both animals and patients. SA3 will compare local measurements of recruitment by PET with the global measures of recruitment by NO uptake kinetics and lung mechanics.
| Harris, R Scott; Fujii-Rios, Hanae; Winkler, Tilo et al. (2012) Ventilation defect formation in healthy and asthma subjects is determined by lung inflation. PLoS One 7:e53216 |
| Harris, R Scott; Venegas, José G; Wongviriyawong, Chanikarn et al. (2011) 18F-FDG uptake rate is a biomarker of eosinophilic inflammation and airway response in asthma. J Nucl Med 52:1713-20 |
| Owens, Robert L; Hess, Dean R; Malhotra, Atul et al. (2008) Effect of the chest wall on pressure-volume curve analysis of acute respiratory distress syndrome lungs. Crit Care Med 36:2980-5 |
| Harris, R Scott; Winkler, Tilo; Tgavalekos, Nora et al. (2006) Regional pulmonary perfusion, inflation, and ventilation defects in bronchoconstricted patients with asthma. Am J Respir Crit Care Med 174:245-53 |
| Harris, R Scott; Hadian, Mehrnaz; Hess, Dean R et al. (2004) Pulmonary artery occlusion increases the ratio of diffusing capacity for nitric oxide to carbon monoxide in prone sheep. Chest 126:559-65 |
