Graduation Year

2018

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Medical Sciences

Major Professor

Kendall Morris, Ph.D.

Committee Member

Javier Cuevas, Ph.D.

Committee Member

Paul Davenport, Ph.D.

Committee Member

Jay Dean, Ph.D.

Committee Member

Thomas Taylor-Clark, Ph.D.

Committee Member

Dana Zeidler, Ph.D.

Keywords

central pattern generators, pulmonary afferents, swallow-breathing coordination

Abstract

Swallowing is an essential motor act that coordinates the movement of food or saliva from the mouth through the pharynx and into the esophagus while protecting the upper airways from aspiration of those materials. Disordered swallowing, or dysphagia, results when bolus movement from the oropharyngeal phase into the esophageal phase is uncoordinated. Dysphagia directly causes or increases the risk of aspiration during swallowing in many clinical pathologies including Parkinson’s disease, Alzheimer’s disease, cerebrovascular incidents (stroke) in addition to being prevalent among the elderly population. The coordination between breathing and swallowing is mediated through the interaction of the swallow and respiratory Central Pattern Generators (CPGs) located in the brainstem. In the pharyngeal phase of swallow respiratory airflow is temporarily interrupted, and then reset, when the bolus moves through the pharyngeal space. The lungs retain enough air during the swallow apnea to protect the lower airways from accidental aspiration of residual bolus material, modulate the latency to initiate the swallow, while providing sensory feedback for processing within the brainstem network. The timing of the pharyngeal phase of swallow with respiration occurs across a continuum of lung volumes. Following swallow, the latency to initiate inspiration of the subsequent respiratory cycle increases. The swallow-mediated increase in cycle duration on respiration may depend upon the central processing of pulmonary afferents that may also affect reconfiguration of the respiratory CPG to express the swallow CPG. The peripheral and central mechanisms of swallow-breathing coordination remain poorly understood. Here, the relationship between central inspiratory output and the resultant mechanical inflation of the lungs was manipulated and dissociated to test the hypothesis that a centrally- and peripherally-mediated “swallow gate” coordinates swallow initiation with central respiratory activity and vagally-mediated pulmonary feedback.

We obtained data from decerebrate adult cats of either sex that fully recovered from isoflurane anesthesia prior to the decerebration procedure. Fictive swallows were elicited using electrical stimulation of the superior laryngeal nerves (SLN) or injection of water (Water) into the pharyngeal cavity. Both stimuli were presented at random during the central respiratory cycle and/or the mechanical ventilation cycle. Mechanical ventilation was either triggered in-phase with phrenic discharge activity or it was set independent of phrenic discharge activity. These two modes of mechanical ventilation facilitated our ability to analyze the collective and individual effect of lower airway feedback on swallow-breathing coordination. The efferent discharge activities were recorded from the right hypoglossal (XII), left phrenic (Phr), left lumbar iliohypogastric (Lum) and right vagus (X) or the right recurrent laryngeal (RLN) nerves using silver bipolar hooked electrodes. All nerve activity was full-wave rectified, amplified, RC integrated (τ=200-500 ms) and low-pass filtered prior to analysis for effects on swallow-breathing coordination across stimulation-ventilation conditions. We observed post-inspiratory type (Post-I) and expiratory type (Exp) swallows that produced discrete effects on central respiratory rhythm across all conditions. The Post-I type swallows disturbed the duration and amplitude of preceding central inspiratory activity, without affecting the duration of central expiratory activity. The Exp type swallows prolonged central expiration but produced no effect on central inspiratory activity. We observed that lung inflation negatively modulated swallow initiation during fixed mechanical ventilation in the absence of central respiratory output, i.e., during central apnea. Most swallow elicited during central apnea initiated during periods of low lower airway afferent feedback. Collectively, these findings extend the role for lower airway feedback beyond its role as a provider of lung afferent surveillance and identifies lower airway feedback as a modulator of swallow-breathing coordination.

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