Our goal in studying Alternative Modes of Mechanical Ventilation is to evaluate strategies of mechanical ventilation which result in the optimal delivery of oxygen to systemic tissues while incurring the minimum adverse effects. In (a) normal lungs, (b) in pulmonary edema, and (c) in lungs with acute airflow obstruction caused by bronchospasm, we will employ and evaluate nonconventional modes of mechanical ventilation. The proposed alternative modes of ventilation include high frequency oscillatory ventilation (HFOV), continuous flow ventilation CFV), and extra-corporeal membrane oxygenation (ECMO), either alone or in combination with some form of conventional mechanical ventilation (CMV). Three groups of experiments are proposed (i) Evaluation of the mechanisms of gas phase mass transport during CFV and HFOV. These experiments, performed in anesthetized dogs and pigs with normal, edematous, or bronchoconstricted lungs, or in hardware airway models, will identify mechanisms of gas mixing within the airways at various airway generations and among various parallel paths, and will relate these flow patterns to gas transport efficiency. These experiments should identify strategies for adjusting overall alveolar ventilation as well as its uniformity among regions. (ii) In the second group of experiments, we will apply these alternative ventilation modalities in models of either acute hypoxemic respiratory failure or bronchoconstriction in order to maintain gas exchange and minimize adverse effect. In this regard we ask four questions: 1) At the same mean alveolar pressure, how can oxygenation be maximized by optimal redistribution of edema fluid (edematous lungs) or by adjustment of ventilatory mode (bronchospasm)? 2) Can mean and peak intrathoracic pressures be reduced with any given ventilatory mode alone or in combination, and does this reduction improve cardiac output and systemic oxygen delivery? 3) How does cyclic alveolar pressure fluctuation influence edema accumulation and clearance? 4) Does cyclic application of high alveolar pressures further lung injury, and can alternative modes of mechanical ventilation abate such additional damage in the short or long term? (iii) In addressing the two broad issues detailed above we should have learned how best to apply mechanical ventilation in low pressure pulmonary edema or in patients in status asthmaticus. In the third group of experiments, our long range goal is to evaluate these approaches in clinical trials in acutely ill patients. In doing so we will evaluate the fundamental gas exchange and hemodynamic abnormalities manifest in acute hypoxemic respiratory failure, then test various modalities in an approach directed by results of earlier animal studies.