We propose to study the mechanisms reponsible for gas exchange impairment during general anesthesia. Our short term objectives are to establish what are the primary mechanisms (e.g. lung volume reduction) responsible for development of lung regions with low ventilation-perfusion ratios (VA/Q) and shunt, as well as to determine the relative importance of possible secondary factors (e.g. mechanical ventilation). Our long-term goal is to design anesthetic techniques which substantially reduce gas exchange impairment due to anesthesia. The methods we plant to use are: 1) Studies of lung volume, blood gases (PO2, PCO2) and distribution of VA/Q ratios while awake and during a) thiopental, b) Halothane, c) Nitrous oxide and halothane anesthesia in both young (20-30 year old) and older (greater than 40 years old) patients, with and without lung disease, all at routine anesthetic levels. 2) Similar studies in healthy sheep, but systematically varying anesthetic level, inspired oxygen and nitrous oxide concentrations, during both spontaneous and mechanical ventilation in the lateral and prone positions. These two lung models (humans and sheep) will be studied by systematically applying known forcing functions as independent variables (e.g. degree of lung disease, soluble gas concentration, anesthetic agent and dose, pattern of breathing) to determine the relative response of measurable dependent variables (e.g. degree of inequality of ventilation and perfusion distribution, lung volume, arterial PO2 and PCO2). The findings from these studies will enable us to quantify the importance of proposed mechanisms (i.e. absorption atelectasis, reduced hypoxic pulmonary vasoconstruction, altered motion of the chest wall and diaphragm). Differences in the pattern and degree of gas exchange impairment for these anesthetic techniques will provide sound physiologic and pharmacologic criteria for both prevention and management of this detrimental change in lung function during anesthesia.