We have developed an unique unanesthetized animal model in which the carotid sinus region can be isolated and perfused independently of the systemic circulation with blood gases, perfusion pressure, and chemistry controlled by the investigators. This will allow us to test the ventilatory effects of specific carotid chemo- and baroreceptor stimuli separately or in conjunction with changes in systemic (and therefore CNS) chemistry or blood pressure. We will address three specific questions; 1. Do carotid chemoreceptor stimuli (physiological levels of K+, norepinephrine, lactic acid) and/or their interactions contribute to exercise hyperpnea? Is there a ventilatory effect of blood gas oscillations? How do these stimuli interact with hypocapnia? 2. What is the effect of central nervous system hypoxia, by itself, on magnitude, stability, and timing of breathing and respiratory muscle recruitment? Does CNS hypoxia contribute to """"""""roll off""""""""? Does CNS hypoxia affect central integration of chemoreceptor afferent input? Does CNS hypoxia affect the relative recruitment of upper airway muscles? Is there an effect of sleep state? Does CNS hypoxia play a role in periodic breathing? 3. Can transient, physiological changes in blood pressure at the carotid sinus contribute to unstable breathing, central apnea, and/or changes in upper airway resistance? Is there interaction between baroreceptor and chemoreceptor feedback? Our new animal model gives us the ability to study fundamental aspects of reflexes involved in cardiorespiratory control in a preparation with intact feedback gains during wakefulness, all stages of sleep, and exercise. These reflexes have direct relevance to the control of upper airway patency, gas exchange, and blood pressure, especially during sleep, and should provide insights into the pathophysiology of sleep disordered breathing. Hyperpnea in response to physical activity is the most common physiological hyperpnea of all, yet its mechanisms are still not well understood. our studies, in a physiological model with intact feedback gains, should also answer several fundamental questions concerning the control of exercise hyperpnea.
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