Biomechanical increase in cervical esophageal wall tension during peristalsis.

During pharyngeal phase of swallowing, circumferential tension of the cervical esophagus (CTE) increases caused by a biomechanical process of laryngeal elevation pulling the cervical esophagus orad. The esophagus contracts longitudinally during esophageal peristalsis, therefore, we hypothesized that CTE increases during esophageal peristalsis by a biomechanical process. We investigated this hypothesis using 28 decerebrate cats instrumented with electromyographic (EMG) electrodes on the pharynx and esophagus, and esophageal manometry. We recorded CTE, distal esophageal longitudinal tension (DET), and orad laryngeal tension (OLT) using strain gauges. Peristalsis was stimulated by injecting saline into esophagus or nasopharynx. We investigated the effects of transecting the pharyngo-esophageal nerve (PEN), hypoglossal nerve (HG), or administering (10 mg/kg iv) hexamethonium (HEX). We found that the durations of CTE and DET increased and OLT decreased simultaneously during the total extent of esophageal peristalsis. CTE duration was highly correlated with DET but not esophageal EMG or manometry. The peak magnitudes of the DET and CTE were highly correlated. After HEX administration, peristalsis in the distal esophagus did not occur, and the duration of the CTE response decreased. PEN transection blocked the occurrence of cricopharyngeal or cervical esophageal response during peristalsis but had no significant effect on the CTE response. HG transection had no significant effect on CTE. We conclude that there is a significant CTE increase, independent of laryngeal elevation or esophageal muscle contraction, which occurs during esophageal peristalsis. This response is a biomechanical process caused by esophageal shortening that occurs during esophageal longitudinal contraction of esophageal peristalsis.NEW & NOTEWORTHY Circumferential tension of cervical esophagus (CTE) increases during esophageal peristalsis. CTE response is correlated with distal longitudinal tension on cervical esophagus during esophageal peristalsis but not laryngeal elevation or esophageal muscle contraction. CTE response is not blocked by transection of motor innervation of laryngeal elevating muscles or proximal esophagus but is temporally reduced after hexamethonium administration. We conclude that the CTE response is a biomechanical effect caused by longitudinal esophageal contraction during esophageal peristalsis.

A biomechanical response of the esophagus participates in swallowing.

Evidence suggests that a biomechanical process participates in esophageal function, but no such function has yet been identified. We investigated the role of a biomechanical process during swallowing in 30 decerebrate cats instrumented using electromyogram (EMG) electrodes, strain gauge force transducers, and manometry. We found that the cervical esophagus has a short-lasting circumferential tension response during the pharyngeal phase of swallowing (CTPP), and a concomitant EMG response. The CTPP magnitude was correlated with magnitudes of contraction of the geniohyoideus, laryngeal elevation force, and esophageal orad elongation force. The magnitude of the CTPP was not correlated with the peak or area under the curve of the concomitant esophageal EMG response. Restricting laryngeal elevation by physical force or transecting the hypoglossal nerves decreased or eliminated the CTPP during swallowing. Elongation of the distal cervical esophagus increased basal circumferential cervical esophageal tension as well as the CTPP. Transecting the vagus or pharyngoesophageal nerves, or administering hexosamine intravenously, had no significant effect on CTPP. We conclude that CTPP is a response to esophageal elongation during laryngeal elevation during the pharyngeal phase of swallowing, which is not caused by muscle contraction or mediated by the nervous system. The CTPP may assist in the distal movement of boluses before activation of the esophageal phase of swallowing, and may serve to prevent esophagopharyngeal reflux. We hypothesize that the CTPP is a biomechanical decrease in elasticity of the circumferential connective tissue of the cervical esophagus caused by the stress of cervical esophageal elongation.NEW & NOTEWORTHY The pharyngeal phase of swallowing includes increased circumferential tension of the cervical esophagus during the pharyngeal phase of swallowing (CTPP). The CTPP is a biomechanical response caused by elongation of the esophagus during laryngeal elevation, and is not caused by muscle contraction or mediated by the nervous system. The CTPP may assist in the distal movement of boluses before activation of the esophageal phase of swallowing, and may serve to prevent esophagopharyngeal reflux.

Fatigability of the external anal sphincter muscles using a novel strength training resistance exercise device.

Exercises involving pelvic floor muscles including repetitive voluntary contractions of external anal sphincter (EAS) musculature have been used to improve fecal incontinence. Muscle fatigue is a prerequisite for successful strength training. However, muscle fatigue induced by these exercises has not been systematically studied. We aimed to assess the fatigability of EAS muscles during various exercise methods. Twelve nulliparous (21 ± 2.7 yr) women were studied. We evaluated fatigue during 40 repetitive 3-s contractions and 30-s long squeeze contractions both with and without an intra-anal compressible resistant load. The sequence of exercises was randomized. This load was provided by the continence muscles Resistance Exerciser Device. Anal canal pressures were recorded by high-resolution manometry. Exercise against a resistive load showed significant decrease in anal contractile integral (CI) and maximum squeeze pressure during repetitive short squeeze contractions compared with exercise without a load. Linear regression analysis showed a significant negative correlation between anal CI and successive contraction against load, suggesting "fatigue." Similar findings were observed for maximum squeeze pressure (slope with load = -4.2, P = 0.0003, vs. without load = -0.9, P = 0.3). Long squeeze contraction against a load was also more susceptible to fatigue than without a load (P < 0.0001). In conclusion, repetitive contractions against a compressible load induce fatigue and thus have the potential to strengthen the anal sphincter contractile function than contractions without a load. Fatigue rate in long squeeze contraction exercises with a load is significantly faster than that without a load, also indicating greater effectiveness in inducing muscle fatigue.NEW & NOTEWORTHY Fecal incontinence is a distressing disorder with a mainstay of treatment being pelvic floor muscle exercises. However, none of these exercises has proven occurrence of fatigability, which is an important prerequisite for successful muscle strengthening in rehabilitative exercises. In this study, we proved that we can fatigue the external anal sphincter muscles more efficiently by providing a resistive load during anal repetitive short squeeze contractions and long squeeze contraction exercise.

Characterization and mechanism of the esophago-esophageal contractile reflex of the striated muscle esophagus.

An esophago-esophageal contractile reflex (EECR) of the cervical esophagus has been identified in humans. The aim of this study was to characterize and determine the mechanisms of the EECR. Cats (n = 35) were decerebrated, electrodes were placed on pharynx and cervical esophagus, and esophageal motility was recorded using manometry. All areas of esophagus were distended to locate and quantify the EECR. The effects of esophageal perfusion of NaCl or HCl, vagus nerve or pharyngoesophageal nerve (PEN) transection, or hexamethonium administration (5 mg/kg iv) were determined. We found that distension of the esophagus at all locations activated EECR rostral to stimulus only. EECR response was greatest when the esophagus 2.5-11.5 cm from cricopharyngeus (CP) was distended. HCl perfusion activated repetitively an EECR-like response of the proximal esophagus only within 2 min, and after ~20 min EECR was inhibited. Transection of PEN blocked or inhibited EECR 1-7 cm from CP, and vagotomy blocked EECR at all locations. Hexamethonium blocked EECR at 13 and 16 cm from CP but sensitized its activation at 1-7 cm from CP. EECR of the entire esophagus exists, which is directed in the orad direction only. EECR of striated muscle esophagus is mediated by vagus nerve and PEN and inhibited by mechanoreceptors of smooth muscle esophagus. EECR of smooth muscle esophagus is mediated by enteric nervous system and vagus nerve. Activation of EECR of the striated muscle esophagus is initially sensitized by HCl exposure, which may have a role in prevention of supraesophageal reflux.NEW & NOTEWORTHY An esophago-esophageal contractile reflex (EECR) exists, which is directed in the orad direction only. EECR of the proximal esophagus can appear similar to and be mistaken for secondary peristalsis. The EECR of the striated muscle is mediated by the vagus nerve and pharyngoesophageal nerve and inhibited by mechanoreceptor input from the smooth muscle esophagus. HCl perfusion initially sensitizes activation of the EECR of the striated muscle esophagus, which may participate in prevention of supraesophageal reflux.

Effects of esophageal acidification on esophageal reflexes controlling the upper esophageal sphincter.

Esophageal acid exposure can alter upper esophageal sphincter (UES) function, but the mechanism is unknown. The aim of this study was to determine the effects of esophageal acid exposure on esophago-UES relaxation (EURR) and contractile (EUCR) reflexes. Cats, decrebrate ( n = 27) or chronic ( n = 4), were implanted with electromyographic electrodes on pharynx, larynx, and esophagus. The esophagus was infused with either NaCl (0.9%) or HCl (0.1 N). The EUCR was activated by balloon distension in acute cats and slow air injection in chronic cats, and the EURR was activated by rapid air injection in both sets of cats. We found that NaCl infused for 15 or 30 min had no effect on EUCR or EURR in acute cats. HCl infused for 15, 30, or 45 min significantly ( P < 0.05) decreased the sensitivity to activate EUCR. HCl infused for 15 min significantly ( P < 0.05) increased and for 45 min significantly ( P < 0.05) decreased sensitivity to activate EURR. In chronic cats, HCl infused for 15 min/day increased sensitivity to activate EURR and decreased ( P < 0.05) sensitivity to activate EUCR after 4 days of infusion. EURR occurred spontaneously during HCl infusions on the 3rd and 4th ( P < 0.05) days of HCl infusion. We conclude that esophageal acid exposure initially sensitizes the esophagus to activation of EURR and desensitizes to activation of EUCR, but with longer exposure desensitizes to both. The alteration in sensitivity to activate EURR and EUCR caused by gastroesophageal reflux may play a role in the generation of supraesophageal reflux. NEW & NOTEWORTHY In acute studies, short-term esophageal acid exposure sensitizes esophagus to activation of esophago-upper esophageal sphincter relaxation response (EURR), whereas longer-term exposure inhibits EURR. Short- or long-term esophageal acid exposure decreases sensitivity to activation of esophago-upper esophageal sphincter contractile response (EUCR). In chronic studies, short-term esophageal acid exposure has the same effects on EURR and EUCR as occur acutely, but these effects take days to develop. Alteration in EURR and EUCR caused by gastroesophageal reflux may play a role in reflux disease.

Pharyngoesophageal and cardiorespiratory interactions: potential implications for premature infants at risk of clinically significant cardiorespiratory events.

The aims of this study were to 1) examine pharyngoesophageal and cardiorespiratory responses to provoking pharyngeal stimuli, and 2) to determine potential contributory factors impacting heart rate (HR) changes to provide insight into cardiorespiratory events occurring in preterm infants. Forty-eight neonates (19 females and 29 males, born at 27.7 ± 0.5 wk; mean ± SE) pending discharge on full oral feeds were studied at 38.7 ± 0.2 wk postmenstrual age using concurrent pharyngoesophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor. Pharyngoesophageal and cardiorespiratory responses (prevalence, latency, and duration) were quantified upon abrupt pharyngeal water stimuli (0.1, 0.3, and 0.5 ml in triplicate). Mixed linear models and generalized estimating equations were used for comparisons between HR changes. Contributory factors included stimulus characteristics and subject characteristics. Of 338 pharyngeal stimuli administered, HR increased in 23 (7%), decreased in 108 (32%), and remained stable in 207 (61%) neonates. HR decrease resulted in repetitive swallowing, increased respiratory-rhythm disturbance, and decreased esophageal propagation rates (all, P < 0.05). HR responses were related to stimulus volume, stimulus flow rate, and extreme prematurity (all, P < 0.05). In preterm infants, HR remains stable in a majority of pharyngeal provocations. HR decrease, due to pharyngeal stimulation, is related to aberrant pharyngoesophageal motility and respiratory dysregulation and is magnified by prematurity. We infer that the observed aberrant responses across digestive, respiratory, and cardiovascular systems are related to maladaptive maturation of the parasympathetic nervous system. These aberrant responses may provide diagnostic clues for risk stratification of infants with troublesome cardiorespiratory events and swallowing difficulty. NEW & NOTEWORTHY Cardiorespiratory rhythms concurrent with pharyngeal, upper esophageal sphincter, and esophageal body responses were examined upon pharyngeal provocation in preterm-born infants who were studied at full-term maturation. Decreased heart rate (HR) was associated with extreme preterm birth and stimulus flow/volume. With HR decrease responses, aerodigestive reflex abnormalities were present, characterized by prolonged respiratory rhythm disturbance, repetitive multiple swallowing, and poor esophageal propagation. Promoting esophageal peristalsis may be a potential therapeutic target.

Interplay of spinal and vagal pathways on esophageal acid-related anterior cingulate cortex functional networks in rats.

Esophageal acid sensory signals are transmitted by both vagal and spinal pathways to the cerebral cortex. The influence and interplay of these pathways on esophageal acid-related functional connectivity has been elusive. Our aim was to evaluate the esophageal acid exposure-related effect on the anterior cingulate cortex (ACC) functional connectivity networks using functional MRI-guided functional connectivity MRI (fcMRI) analysis. We studied six Sprague-Dawley rats for fcMRI experiments under dexmedetomidine hydrochloride anesthesia. Each rat was scanned for 6 min before and after esophageal hydrochloric acid infusion (0.1 N, 0.2 ml/min). The protocol was repeated before and after bilateral cervical vagotomy on the same rat. Seed-based fcMRI analysis was used to examine ACC networks and acid-induced network alterations. Three-factor repeated-measures ANOVA analysis among all four subgroups revealed that the interaction of acid infusion and bilateral vagotomy was mainly detected in the hypothalamus, insula, left secondary somatosensory cortex, left parietal cortex, and right thalamus in the left ACC network. In the right ACC network, this interaction effect was detected in the caudate putamen, insula, motor, primary somatosensory cortex, secondary somatosensory cortex, and thalamic regions. These regions in the ACC networks showed decreased intranetwork connectivity due to acid infusion. However, after bilateral vagotomy, intranetwork connectivity strength inversed and became stronger following postvagotomy acid infusion. Signals transmitted through both the vagal nerve and spinal nerves play a role in esophageal acid-related functional connectivity of the ACC. The vagal signals appear to dampen the acid sensation-related functional connectivity of the ACC networks. NEW & NOTEWORTHY These studies show that esophageal acid-induced brain functional connectivity changes are vagally mediated and suggest that signals transmitted through both the vagal nerve and spinal nerves play a role in esophageal acid-related functional connectivity of the anterior cingulate cortex. This paper focuses on the development of a novel rat functional MRI model fostering improved understanding of acid-related esophageal disorders.

Older Age Reduces Upper Esophageal Sphincter and Esophageal Body Responses to Simulated Slow and Ultraslow Reflux Events and Post-Reflux Residue.

BACKGROUND & AIMS: It is not clear how age affects airway protective mechanisms. We investigated the effects of aging on upper esophageal sphincter (UES) and esophageal body pressure responses to slow and ultraslow simulated reflux events and post-reflux residue. METHODS: We performed a prospective study of 11 elderly (74 ± 9 years old) and 11 young (28 ± 7 years old) healthy volunteers. Participants were placed in a supine position and evaluated by concurrent high-resolution impedance manometry and an esophageal infusion technique. Potential conditions of gastroesophageal reflux were simulated, via infusion of 0.1 N HCl and saline. UES and esophageal pressure responses were measured during the following: slow infusion (1 mL/s) for 60 seconds, 60 seconds of postinfusion dwell period, ultraslow infusion (0.05 mL/s) for 60 seconds, and 60 seconds of a postinfusion dwell period. All infusions were repeated 3 times. We used the UES high-pressure zone contractile integral (UES-CI) to determine responses of the UES. RESULTS: Young and elderly subjects each had a significant increase in the UES-CI during slow infusions and during entire passive dwell intervals compared with baseline (P < .01, both groups). Ultraslow infusions were associated with a significant increase in UES-CI in only the young group, in the late infusion period, and into the dwell interval (P < .01). During the slow infusions and their associated dwell periods, young subjects had a higher frequency of secondary peristalsis than elderly subjects (P < .05). There was more secondary peristalsis during active infusions than dwell intervals. Secondary peristalsis was scarce during ultraslow infusions in both groups. CONCLUSIONS: UES and esophageal body pressure responses to low-volume ultraslow reflux and associated post-reflux residue are reduced in elderly individuals. This deterioration could have negative effects on airway protection for people in this age group.

The effect of body position on esophageal reflexes in cats: a possible mechanism of SIDS?

BackgroundIt has been hypothesized that life-threatening events are caused by supraesophageal reflux (SER) of gastric contents that activates laryngeal chemoreflex-stimulated apnea. Placing infants supine decreases the risk of sudden infant death syndrome (SIDS). The aim of this study was to determine whether body position affects esophageal reflexes that control SER.MethodsWe instrumented the pharyngeal and esophageal muscles of decerebrate cats (N=14) to record EMG or manometry, and investigated the effects of body position on the esophago-upper esophageal sphincter (UES) contractile reflex (EUCR), esophago-UES relaxation reflex (EURR), esophagus-stimulated pharyngeal swallow response (EPSR), secondary peristalsis (SP), and pharyngeal swallow (PS). EPSR, EUCR, and SP were activated by balloon distension, EURR by air pulse, and PS by nasopharyngeal water injection. The esophagus was stimulated in the cervical, proximal thoracic, and distal thoracic regions. The threshold stimulus for activation of EUCR, EURR, and PS, and the chance of activation of EPSR and SP were quantified.ResultsWe found that only EPSR was significantly more sensitive in the supine vs. prone position regardless of the stimulus or the position of the stimulus in the esophagus.ConclusionWe hypothesize that the EPSR may contribute to the protection of infants from SIDS by placement in the supine position.

Defining pharyngeal contractile integral during high-resolution manometry in neonates: a neuromotor marker of pharyngeal vigor.

BACKGROUND: Pharyngeal contractility is critical for safe bolus propulsion. Pharyngeal contractile vigor can be measured by Pharyngeal Contractile Integral (PhCI): product of mean pharyngeal contractile amplitude, length, and duration. We characterized PhCI in neonates and examined the hypothesis that PhCI differs with mode of stimulation. METHODS: Nineteen neonates born at 38.6 (34-41) weeks gestation were evaluated at 42.9 (40.4-44.0) weeks postmenstrual age using high-resolution manometry (HRM). PhCI was calculated using: (a) Conventional and (b) Automated Swallow Detection algorithm (ASDA) methods. Contractility metrics of all pharyngeal regions were examined using mixed statistical models during spontaneous and adaptive state (pharyngeal and oral stimulus) swallowing. RESULTS: PhCI of oral stimuli swallows were distinct from pharyngeal stimuli and spontaneous swallows (P < 0.05). Correlation between conventional and ASDA methods was high (P < 0.001). PhCI increased with swallows for pharyngeal stimulation (P < 0.05) but remained stable for swallows with oral stimulation. PhCI differed between proximal and distal pharynx (P < 0.001). CONCLUSIONS: PhCI is a novel reliable metric capable of distinguishing (1) proximal and distal pharyngeal activity, (2) effects of oral and pharyngeal stimulation, and (3) effects of prolonged stimulation. Changes in pharyngeal contractility with maturation, disease, and therapies can be examined with PhCI.

Maturation Modulates Pharyngeal-Stimulus Provoked Pharyngeal and Respiratory Rhythms in Human Infants.

Pharyngeal-provocation induced aerodigestive symptoms in infants remain an enigma. Sources of pharyngeal provocation can be anterograde as with feeding, and retrograde as in gastroesophageal reflux. We determined maturational and dose-response effects of targeted pharyngeal-stimulus on frequency, stability, and magnitude of pharyngeal and respiratory waveforms during multiple pharyngeal swallowing responses in preterm-born infants when they were of full-term postmenstrual age (PMA). Eighteen infants (11 male) were studied longitudinally at 39.8 ± 4.8 weeks PMA (time-1) and 44.1 ± 5.8 weeks PMA (time-2). Infants underwent concurrent pharyngo-esophageal manometry, respiratory inductance plethysmography, and nasal airflow thermistor methods to test sensory-motor interactions between the pharynx, esophagus, and airway. Linear mixed models were used and data presented as mean ± SEM or %. Overall, responses to 250 stimuli were analyzed. Of the multiple pharyngeal swallowing responses (n = 160), with maturation (a) deglutition apnea duration decreases (p < 0.01), (b) number of pharyngeal waveform peaks and duration decreases for initial responses (p < 0.01), and subsequent responses have lesser variation and greater stability (p < 0.01). With increment in stimulus volumes we noted (a) increased prevalence (%) of pharyngeal responses (p < 0.05), (b) increased number of pharyngeal peaks (p < 0.05), yet pharyngeal frequency (Hz), variability, and stability remain unaffected (p > 0.05), and (c) respiratory changes were unaffected (p > 0.05). Initial and subsequent pharyngeal responses and respiratory rhythm interactions become more distinct with maturation. Interval oromotor experiences and volume-dependent increase in adaptive responses may be contributory. These mechanisms may be important in modulating and restoring respiratory rhythm normalcy.

Characterization and mechanisms of the supragastric belch in the cat.

A response in which a belch occurs without gastric involvement, i.e., the supragastric belch (SGB), has been characterized in humans. The aims of this study were to determine whether animals have an SGB and, if so, to determine its mechanisms. Studies were conducted in decerebrate cats (n = 30) with electromyographic electrodes on hyoid, pharyngeal, esophageal, and diaphragm muscles. The effects of distending different regions of the esophagus in different manners using a balloon were quantified to determine the most appropriate stimulus for activating the cat SGB. The effects of esophageal perfusion of lidocaine (n = 3), vagus nerve transection (n = 3), or esophageal acidification (n = 5) on activation of the SGB were determined. Rapid large distensions of the thoracic esophagus best activated responses similar to the human SGB, i.e., rapid inhalation followed by a belch. The rapid inhalation was associated with activation of hiatal fibers and the belch with activation of dome fibers of the diaphragm. The rapid inhalation response was independent of the belch response. Lidocaine perfusion of the esophagus blocked the belch response without blocking the rapid inhalation, HCl perfusion sensitized the esophagus to activation of both the rapid inhalation and the belch response, and vagotomy blocked both responses. We conclude that the cat has an SGB that is composed of two independent reflex responses, i.e., rapid inhalation and belch, that are mediated by the vagus nerves and tension/mucosal receptors of the esophagus and sensitized by esophageal acid exposure. We hypothesize that the SGB is a learned voluntarily activated reflex response.NEW & NOTEWORTHY Rapid strong distension of the thoracic esophagus activates rapid inhalation followed by a belch, which is the sequence of responses that compose the human supragastric belch (SGB). The rapid inhalation and belch phases of the cat SGB are activated by hiatal and dome fibers of the diaphragm, respectively, and are mediated by the vagus nerves and tension/mucosal receptors of the esophagus and sensitized by esophageal acid exposure. There are many similarities between the cat and human SGB.

Pharyngeal peristaltic pressure variability, operational range, and functional reserve.

The present understanding of pharyngeal motor function remains incomplete. Among the remaining gaps of knowledge in this regard is the magnitude of variability of pharyngeal peristaltic pressure amplitude. Although variability can pose difficulty in interpretation of manometric findings, its magnitude can inform the operational range and reserve of the pharyngeal contractile function. We aimed to define the intra- and intersubject and intersession variability of select pharyngeal manometric parameters and, using this information, determine the number of swallow repetitions for acquiring reliable pharyngeal manometric data. We recorded pharyngeal peristalsis in 10 healthy subjects (age: 50 ± 25 yr, 5 women) by high-resolution manometry during two separate sessions of 20 sequences of 0.5-ml water swallows. Two-way ANOVA showed significant variation in the mean peak peristaltic pressure value across sites (P < 0.0001) as well as within the data at each site (P < 0.0001). Similarly, the pharyngeal contractile integral exhibited significant inter- (P = 0.003) and intrasubject (P < 0.001) variability. The Shapiro-Wilk normality test showed mixed results, in that some sites showed normally distributed data, whereas others did not. A robust Monte Carlo simulation showed that the nominal sample size was different for various tested metrics. For a power of 0.8, commonly accepted as an adequate threshold for acceptable statistical power, the optimal sample size for various peristaltic parameters ranged between 3 and 15. There is significant intra- and intersubject variability in site-specific and integrated parameters of pharyngeal peristalsis. The observed variance indicates a significant operational range and reserve in pharyngeal contractile function while necessitating parameter-specific sample size for reliable results.NEW & NOTEWORTHY Intra- and intersubject variability are significant and different at various sites within the contractile pharynx. In addition, significant swallow-to-swallow and subject-to-subject variability exists in pharyngeal contractile integral. The range of intrasubject variability indicates the existence of broad operational range and reserve. Lastly, our variability studies informed Monte Carlo and power analyses, yielding estimates of sample size that would ensure accurate representation of pressure metric variability.

Reduced Functional Connectivity Between the Hypothalamus and High-order Cortical Regions in Adolescent Patients With Irritable Bowel Syndrome.

The hypothalamus plays a critical role in maintaining visceral homeostasis. Altered hypothalamus activation has been implicated in functional gastrointestinal disorders, including irritable bowel syndrome (IBS). One important aspect of homeostatic regulation is the cortical modulation of limbic and paralimbic subsystems, including the hypothalamus, which in turn affects the descending regulatory processes mediating visceral homeostasis. Using neuroimaging, we evaluated hypothalamus functional connectivity in adolescent patients with IBS and age-matched healthy controls who received rectal distension stimulations. More extensive hypothalamus connectivity was observed in liminal than subliminal condition in controls, but not in patients with IBS. Compared with controls, patients with IBS showed significantly reduced hypothalamus connectivity in the bilateral prefrontal cortices, supplementary motor and premotor areas, bilateral sensorimotor cortex, and limbic subareas, which are specifically involved in homeostatic regulation. The findings support the generalized homeostatic regulation model that reduced cortical and limbic modulations of hypothalamus functioning underlies disrupted visceral homeostasis in patients with IBS.

Effects of laryngeal restriction on pharyngeal peristalsis and biomechanics: Clinical implications.

To date, rehabilitative exercises aimed at strengthening the pharyngeal muscles have not been developed due to the inability to successfully overload and fatigue these muscles during their contraction, a necessary requirement for strength training. The purpose of this study was to test the hypothesis that applying resistance against anterosuperior movement of the hyolaryngeal complex will overload the pharyngeal muscles and by repetitive swallowing will result in their fatigue manifested by a reduction in pharyngeal peristaltic amplitude. Studies were done in two groups. In group 1 studies 15 healthy subjects (age: 42 ± 14 yr, 11 females) were studied to determine whether imposing resistance to swallowing using a handmade device can affect the swallow-induced hyolaryngeal excursion and related upper esophageal sphincter (UES) opening. In group 2, an additional 15 healthy subjects (age 56 ± 25 yr, 7 females) were studied to determine whether imposing resistance to the anterosuperior excursion of the hyolaryngeal complex induces fatigue manifested as reduction in pharyngeal contractile pressure during repeated swallowing. Analysis of the video recordings showed significant decrease in maximum deglutitive superior laryngeal excursion and UES opening diameter (P < 0.01) due to resistive load. Consecutive swallows against the resistive load showed significant decrease in pharyngeal contractile integral (PhCI) values (P < 0.01). Correlation analysis showed a significant negative correlation between PhCI and successive swallows, suggesting "fatigue" (P < 0.001). In conclusion, repeated swallows against a resistive load induced by restricting the anterosuperior excursion of the larynx safely induces fatigue in pharyngeal peristalsis and thus has the potential to strengthen the pharyngeal contractile function.

A human model of restricted upper esophageal sphincter opening and its pharyngeal and UES deglutitive pressure phenomena.

Oropharyngeal dysphagia due to upper esophageal sphincter (UES) dysfunction is commonly encountered in the clinical setting. Selective experimental perturbation of various components of the deglutitive apparatus can provide an opportunity to improve our understanding of the swallowing physiology and pathophysiology. The aim is to characterize the pharyngeal and UES deglutitive pressure phenomena in an experimentally induced restriction of UES opening in humans. We studied 14 volunteers without any dysphagic symptoms (7 men, 66 ± 11 yr) but with various supraesophageal reflux symptoms. To induce UES restriction, we used a handmade device that with adjustment could selectively apply 0, 20, 30, or 40 mmHg pressure perpendicularly to the cricoid cartilage. Deglutitive pharyngeal and UES pressure phenomena were determined during dry and 5- and 10-ml water swallows × 3 for each of the UES perturbations. External cricoid pressure against the UES resulted in a significant increase in hypopharyngeal intrabolus pressure and UES nadir deglutitive relaxation pressure for all tested swallowed volumes (P < 0.05). Application of external cricoid pressure increased the length of the UES high pressure zone from 2.5 ± 0.2 to 3.1 ± 0.2, 3.5 ± 0.1, and 3.7 ± 0.1 cm for 20, 30, and 40 mmHg cricoid pressure, respectively (P < 0.05). External cricoid pressure had no significant effect on pharyngeal peristalsis. On the other hand, irrespective of external cricoid pressure deglutitive velopharyngeal contractile integral progressively increased with increased swallowed volumes (P < 0.05). In conclusion, acute experimental restriction of UES opening by external cricoid pressure manifests the pressure characteristics of increased resistance to UES transsphincteric flow observed clinically without affecting the pharyngeal peristaltic contractile function.

Characterization and mechanisms of the pharyngeal swallow activated by stimulation of the esophagus.

Stimulation of the esophagus activates the pharyngeal swallow response (EPSR) in human infants and animals. The aims of this study were to characterize the stimulus and response of the EPSR and to determine the function and mechanisms generating the EPSR. Studies were conducted in 46 decerebrate cats in which pharyngeal, laryngeal, and esophageal motility was monitored using EMG, strain gauges, or manometry. The esophagus was stimulated by balloon distension or luminal fluid infusion. We found that esophageal distension increased the chance of occurrence of the EPSR, but the delay was variable. The chance of occurrence of the EPSR was related to the position, magnitude, and length of the stimulus in the esophagus. The most effective stimulus was long, strong, and situated in the cervical esophagus. Acidification of the esophagus activated pharyngeal swallows and sensitized the receptors that activate the EPSR. The EPSR was blocked by local anesthesia applied to the esophageal lumen, and electrical stimulation of the recurrent laryngeal nerve caudal to the cricoid cartilage (RLNc) activated the pharyngeal swallow response. We conclude that the EPSR is activated in a probabilistic manner. The receptors mediating the EPSR are probably mucosal slowly adapting tension receptors. The sensory neural pathway includes the RLNc and superior laryngeal nerve. We hypothesize that, because the EPSR is observed in human infants and animals, but not human adults, activation of EPSR is related to the elevated position of the larynx. In this situation, the EPSR occurs rather than secondary peristalsis to prevent supraesophageal reflux when the esophageal bolus is in the proximal esophagus.

Effect of nasal noninvasive respiratory support methods on pharyngeal provocation-induced aerodigestive reflexes in infants.

The pharynx is a locus of provocation among infants with aerodigestive morbidities manifesting as dysphagia, life-threatening events, aspiration-pneumonia, atelectasis, and reflux, and such infants often receive nasal respiratory support. We determined the impact of different oxygen delivery methods on pharyngeal stimulation-induced aerodigestive reflexes [room air (RA), nasal cannula (NC), and nasal continuous positive airway pressure (nCPAP)] while hypothesizing that the sensory motor characteristics of putative reflexes are distinct. Thirty eight infants (28.0 ± 0.7 wk gestation) underwent pharyngoesophageal manometry and respiratory inductance plethysmography to determine the effects of graded pharyngeal stimuli (n = 271) on upper and lower esophageal sphincters (UES, LES), swallowing, and deglutition-apnea. Comparisons were made between NC (n = 19), nCPAP (n = 9), and RA (n = 10) groups. Importantly, NC or nCPAP (vs. RA) had: 1) delayed feeding milestones (P < 0.05), 2) increased pharyngeal waveform recruitment and duration, greater UES nadir pressure, decreased esophageal contraction duration, decreased distal esophageal contraction amplitude, and decreased completely propagated esophageal peristalsis (all P < 0.05), and 3) similarly developed UES contractile and LES relaxation reflexes (P > 0.05). We conclude that aerodigestive reflexes were similarly developed in infants using noninvasive respiratory support with adequate upper and lower aerodigestive protection. Increased concern for GERD is unfounded in this population. These infants may benefit from targeted oromotor feeding therapies and safe pharyngeal bolus transit to accelerate feeding milestones.

Impaired upper esophageal sphincter reflexes in patients with supraesophageal reflux disease.

BACKGROUND & AIMS: Normal responses of the upper esophageal sphincter (UES) and esophageal body to liquid reflux events prevent esophagopharyngeal reflux and its complications, however, abnormal responses have not been characterized. We investigated whether patients with supraesophageal reflux disease (SERD) have impaired UES and esophageal body responses to simulated reflux events. METHODS: We performed a prospective study of 25 patients with SERD (age, 19-82 y; 13 women) and complaints of regurgitation and supraesophageal manifestations of reflux. We also included 10 patients with gastroesophageal reflux disease (GERD; age, 32-60 y; 7 women) without troublesome regurgitation and supraesophageal symptoms and 24 healthy asymptomatic individuals (controls: age, 19-49 y; 13 women). UES and esophageal body pressure responses, along with luminal distribution of infusate during esophageal rapid and slow infusion of air or liquid, were monitored by concurrent high-resolution manometry and intraluminal impedance. RESULTS: A significantly smaller proportion of patients with SERD had UES contractile reflexes in response to slow esophageal infusion of acid than controls or patients with GERD. Only patients with SERD had abnormal UES relaxation responses to rapid distension with saline. Diminished esophageal peristaltic contractions resulted in esophageal stasis in patients with GERD or SERD. CONCLUSIONS: Patients with SERD and complaints of regurgitation have impaired UES and esophageal responses to simulated liquid reflux events. These patterns could predispose them to esophagopharyngeal reflux.