The long-term objective of this research is to test the hypothesis that knowledge of regional lung mechanical and ventilatory function can be used to improve the outcome of acute lung injury (ALI) and ARDS. ALI/ARDS is a form of respiratory failure characterized by the progressive deterioration of the gas exchange and mechanical properties of the lung occurring after a non-specific initiating injury. The primary treatment, mechanical ventilation with PEEP, ironically can promote the progression of the disease from regional to global, trading off oxygenation against further injury from high pressures and overdistension. ARDS, particularly in its early stages represents an inhomogeneous mechanical process in the lung, and a complete understanding of its pathogenesis and treatment has been hampered by the difficulty in measuring regional lung function. the proposed studies will use the oleic acid animal model of ALI and novel non-invasive CT imaging methods to investigate the relationship between regional ventilation and volume recruitment with PEEP in anesthetized dogs. Ventilation in lung regions as small as 1 ml volume will be determined form the washin/washout of stable xenon gas, measured on serial CT scans. Regional lung mechanical properties and recruitment will be determined from changes in aeration of the lungs determined from CT images at different PEEP levels. The first two Specific Aims relate traditional whole lung measurements of mechanical properties with regional lung mechanical properties, regional patterns of aeration, and regional ventilation distribution, testing several controversial assumptions currently driving clinical practice in mechanical ventilation of patients with ARDS.
Specific Aim 3 examines the relationship between end-expiratory and end-inspiratory volume on volume recruitment and regional ventilation, looking particularly at the trade-off between regional overdistension vs. recruitment.
Specific Aim 4 applies the knowledge gained in the earlier studies to explain the improvements in oxygenation seen in the switch from supine to prone position after acute lung injury in terms of changes in regional mechanical function and ventilation distribution. These studies will add insight into the pathophysiology and treatment of ALI by allowing the currently available global measurements of lung dysfunction, such as the inspiratory P-V curve, to be interpreted on a regional level. The results will provide the basis for further animal and human studies of regional mechanics in ALI as well as provide data and a rationale to guide clinical therapy.
