Apnea is clinically important since it is strongly correlated with major neurologic deficits and possibly sudden unexplained death, One cause for central apnea, especially in the pre-term infant, is activation of the laryngeal chemoreflex through discoordinated swallowing or regurgitation of food. Under some conditions, defense mechanisms (e.g. coughing, swallowing) are impaired or immature leaving the threat of protracted apnea and cyanosis. Despite the potential importance of this reflex, little is known of the central pathway over which this reflex is propagated or what activates mechanisms to re-initiate breathing. Our preliminary results have shown that superior laryngeal nerve (SLN) stimulation induces periodic breathing, hypoxia and hypercapnia which lasts throughout the period of stimulation. Breaths are initiated despite the continuation of he SLN stimulus and these breaths are associated with behavioral arousal. These breaths may be eliminated with sub-surgical doses of anesthetics resulting in prolonged apneas, cyanosis and cardiorespiratory collapse. Studies proposed in this grant will use laryngeal receptor activation to answer several questions; 1) What are the model sensitivities, termination sites and secondary neuronal effects from physiologically identified laryngeal receptors? 2) By what mechanism is the apnea terminated including the roles of pulmonary afferents, chemoreceptors and physiologically identified subgroups of respiratory neurons? We propose to answer these questions by 1) measuring ventilation (barometric method), heart rate and blood pressure during activation of the laryngeal reflex in unanesthetized intact and unanesthetized decerebrate piglets, 2) defining the reflex pathway by anatomically tracing modal specific afferents centrally and examining the post-synaptic changes induced by stimulation of these afferents. Axonal tracing is done by horseradish peroxidase transport and antidromic stimulation; post-synaptic effects are studied by intracellular recording from respiratory related neurons which are physiologically characterized. The anticipated results of this work will identify the areas of the respiratory control system which are of particular importance in causing and terminating central apnea, and so may lead to better therapeutic modalities in the treatment of those infants subject to life threatening apneas.
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