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A Human Model of Restricted UES Opening and Its Characteristic Pharyngealand UES Deglutitive Pressure PhenomenaHongmei Jiao, Ling Mei, Arash Babaei, Tarun Sharma, Patrick Sanvanson, Mark Kern,Sudarshan R. Jadcherla, Reza Shaker

Introduction: Human disease models can help to better understand the pathophysiology andsystematically characterize its consequences. Upper esophageal sphincter (UES) dysphagia isa common sequela of a number of disorders including CVA, reflux disease and aging.Intrinsic disorders of the UES such as fibrosis and inflammation can result in its diminisheddistensibility and restrict its opening causing dysphagia. Aim: To characterize the pharyngealand UES deglutitive pressure phenomena in an experimentally induced restricted UES modelin humans. Methods: We studied 15 patients (8 male, age 65±11 years) with varioussupraesophageal reflux symptoms. To induce UES restriction, we used a handmade simpledevice comprised of two components that could be comfortably worn around the neck: anelastic band and a cushion (5 X 3 X 2.5 CM). The cushion was placed horizontally at thecenter of the cricoid cartilage. By adjusting the elastic band, we selectively applied 0, 20,30, 40 mmHg pressure perpendicular to the cricoid laryngeal structure inducing equivalentresistance against UES opening. In this model, the UES, in addition to relaxation, has toovercome the externally imparted pressure to open. Deglutitive pharyngeal and UES pressurephenomena were determined using high-resolution manometry, which recorded from entirepharynx, UES and proximal esophagus. We tested dry, 5 and 10ml swallows x 3. Results:Application of the external pressure band increased the length of the UES high pressurezone from 2.5 cm without the band to 3.1, 3.5 and 3.7 cm for 20, 30, 40mmHg cricoidrestrictive pressure, respectively (p<0.05). Increased restrictive pressure against UES resultedin a significant increase in hypopharyngeal intra-bolus pressure (IBP) during all swallowedvolumes (figure). Similarly, increased UES restrictive pressure resulted in increased UESnadir deglutitive relaxation pressure for all swallowed volumes (table, p<0.05). Swallowedvolume had no effect on pharyngeal peak pressure, duration or velocity. None of these wereaffected by restrictive external UES pressures. Deglutitive velopharygeal pressure progres-sively increased with increased swallowed volume (p<0.05). These pressures were also notaffected by UES restrictive external pressure. Conclusions: Acute experimental restriction ofUES opening by external cricoid pressure in humans manifests the pressure characteristicsof increased resistance to UES trans-sphincteric flow observed in disorders that are accompa-nied by reduced UES opening. These pressure characteristics include increased hypopharyn-geal intra-bolus as well as nadir deglutitive UES relaxation pressures. This model canpotentially be helpful in better understanding of UES pathophysiology.The effect of external cricoid (UES restrictive) pressure on UES nadir pressure

* P <0.05: compared with UES external restrictive pressure of zero # P <0.05: comparedwith dry swallow DS: dry swallow

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Pharyngeal Electrical Stimulation (PES) Expedites Swallowing Recovery inDysphagia Post-Acute Stroke: a Phase II Double-Blinded RandomisedControlled TrialDipesh H. Vasant, Emilia Michou, Pippa Tyrrell, Satish Mistry, Vanoo Jayasekeran,Shaheen Hamdy

Introduction: Post-stroke dysphagia has a high-prevalence and potentially devastating conse-quences including aspiration pneumonia and death. Swallowing recovery occurs in somecases but can take several months with current therapies having limited evidence-base.Pharyngeal Electrical Stimulation (PES) is a promising treatment, already known to activatepharyngeal motor pathways and in pilot studies in acute stroke improved swallowing function

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2-weeks post treatment [1-2]; however the longer-term effects on swallowing remain unex-plored. Methods: 36 hospitalised patients with new-onset dysphagia (22 males, mean age70 ± 2.1 years), were recruited within 6 weeks of stroke after failing a standardised swallowingscreening test [3]. Patients were randomised with an intention-to-treat approach to eitherActive (n=18) or Sham (n=18) PES via an intraluminal pharyngeal catheter at 5Hz, at 75%maximum-tolerated intensity for 10 minutes, for 3 days. A validated Dysphagia SeverityRating (DSR) scale (0-12 (normal-severe)) [2] was applied by independent, blinded speechtherapists at baseline, 2-weeks and 3-months post-intervention. Data were compared usingnon-parametric tests (Mann-Whitney U test). Results: Active but not Sham PES improvedDSR at 2-weeks (Figure 1), (Active: baseline median 9 (Inter-Quartile Range (IQR) 4-12),2-weeks median 3 (IQR 1-9), U=81,*p=0.015, Sham: baseline median 7 (IQR 3-10), 2-weeks median 3 (IQR 1-8), U=103.5, p=0.1). By 3-months, compared to baseline swallowingthere was overall improvement in DSR in both groups (Active: 3-months median 0 (IQR 0-3), U=43.5, **p=0.001, Sham: 3-months median 1 (IQR 0-3), U=52, **p=0.001). Discussion:These data provide further evidence that PES expedites swallowing recovery in post-strokedysphagia compared to standard therapy, an effect that is maintained at 3-months afterintervention. References: 1. Fraser, C., et al., Neuron 2002. 2. Jayasekeran, V., et al.,Gastroenterology, 2010. 3. Martino, R., et al., Stroke, 2009.

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Maturation and Stimulus-Volumes Modulate Pharyngeal Provocation InducedPharyngeal Rhythms in Human Premature InfantsKathryn Hasenstab, Xiaoyu Gao, Sudarshan Jadcherla

BACKGROUND: Swallowing and breathing dysregulation is a frequent problem in neonatesthat interferes with efficient oral intake and delays growth and hospital discharge. Effectsof maturation and stimulus volumes on the variability of respiratory and pharyngeal rhythmsas well as pharyngeal reflexive swallowing (PRS) are unclear. AIMS: To determine the effectof a) maturation and b) graded pharyngeal stimulus-volumes on the frequency, stability andmagnitude of pharyngeal and respiratory interactions. METHODS: 18 infants (11 male, 23to 37 wks gestation) were studied at 40 and 45 wks postmenstrual age (PMA) using concurrentpharyngo-esophageal manometry, respiratory inductance plethysmography, and nasal airflowthermistor to test pharyngeal and respiratory interactions upon graded water stimuli (0.1,0.3, 0.5 ml, in triplicate). Respiratory adaptation measures included frequency and durationof deglutition apnea. Upon pharyngeal stimulation, initial pharyngeal response was definedas the first pharyngeal burst and composite pharyngeal response was defined as presenceof pharyngeal activity until the terminal swallow restored aerodigestive quiescence to respira-tory and esophageal normalcy. Recruitment, frequency, variability, and stability of initialand composite pharyngeal responses were characterized. Linear mixed, GEE, and generalizedlinear models were applied; data presented as median (IQR), mean ± SEM, or %. RESULTS:Overall, 250 stimuli were given. Prevalence (%) of feeding methods (gavage: transitional:full oral) at 40 wks vs. 45 wks PMA were 17:44:39 vs. 0:0:100 respectively (P<0.01).Background number of clinically significant cardiopulmonary events (CSCPE) 1-wk priorto initial vs. subsequent evaluations respectively were: 12.5 ± 16.8 vs. 4.4 ± 5.6 (P=0.05).Number of CSCPEs during feeding 1-wk prior to initial vs. subsequent evaluations respec-tively were: 5.6 ± 9.1 vs. 1.9 ± 2.6 (P=0.05). As stimulus volume increases, pharyngealresponse recruitment increases (β ± SE, 7.7 ± 2.0, P<0.01) and duration increases (β ± SE,12.8 ± 2.8, P<0.01). Respiratory and pharyngeal response characteristics are shown (Table1). CONCLUSIONS: 1) Brain stem-modulated vagal and respiratory pathways undergofurther maturation. 2) Volume-dependent increase in recruitment of adaptive responsesoccur. 3) Maturation modulates pharyngeal reflexes and respiratory adaptation by the follow-ing regulatory mechanisms: a) The occurrence of deglutition apnea is similar, but durationdecreases with maturation. b) Pharyngeal waveform recruitment and duration decreases withmaturation. c) Frequency, variability and stability of the pharyngeal waveforms in the initialburst are similar. d) Although pharyngeal waveform frequency is similar, variability andstability of the composite burst is improved with maturation. *Supported in part by 2RO1DK068158 (Jadcherla)Table 1. Effect of maturation on pharyngeal stimulation induced respiratory and pharyn-geal rhythms

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