We propose to investigate the reflex functions and afferent characteristics of pulmonary nerve endings responsive to stimuli delivered via the pulmonary vasculature and airways. Our studies will concentrate on those stimuli that are likely to provide useful data from which we may better understand the physiologic role of pulmonary vagal afferent nerves and how these afferents interact in the control of breathing and the maintenance of bronchomotor tone. We will more completely characterize the respiratory reflexes elicited by changes in pulmonary arterial PCO2, pulmonary congestion, ozone exposure and lung deflation. To accomplish these studies, we will utilize a double cardiopulmonary bypass preparation which will allow us to control blood flow, venous pressures, and blood gases in the pulmonary circulation independently of those in the systemic circulation. Systemic venous return will be removed from the right atrium of anesthetized dogs and pigs and will then be pumped through a membrane gas exchanger, heat exchanger and returned to the aorta. An identical bypass will be established for the pulmonary circulation, removing blood from the left atrium and returning it to the pulmonary artery. With this preparation, we will assess changes in breathing pattern and airway smooth muscle tone. Breathing pattern will be assessed by ventilating the lungs with a phrenic driven servo-controlled respirator, thus volume feedback from the lungs will function normally and the ventilator cycles may be considered as """"""""breaths"""""""". Airway tone will be assessed by measuring the tension in an isolated tracheal segment. We will also investigate the response of vagal afferent nerve endings to various pulmonary stimuli. We shall record impulses from """"""""single"""""""" fibers supplying the various different types of pulmonary afferents, examining their response to graded stimuli. In particular, we shall examine the response of lung C-fibers to CO2, elevations of pulmonary venous pressure and varying concentrations of ozone. We will also attempt to examine the response of rapidly adapting receptors to CO2 and to quantify their activity as a function of lung volumes below FRC in a manner similar to that reported for these fibers at lung volumes above FRC.
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