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. METHODS: We investigated this hypothesis using 28 decerebrate cats instrumented with 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). RESULTS: 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. CONCLUSION: 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.

Physiology of the Digestive Tract Correlates of Vomiting.

Emesis is composed of 3 independent digestive tract correlates that are individually organized by a brainstem neural network and all 3 hierarchically organized by a central pattern generator. The central pattern generator may be in the Bötzinger nucleus of the brain stem. The digestive tract sensory mechanisms that activate vomiting are the digestive tract mucosa or chemoreceptive trigger zone of the area postrema. Regardless of the initial stimulus, the area postrema may be activated in order to inhibit orthograde digestive tract motility and reflux blocking reflexes that would interfere with anterograde movement, which is the basic purpose of vomiting. The digestive tract correlates are (1) relaxation of the upper stomach and contraction of the lower pharynx, (2) retrograde giant contraction, and (3) the pharyngo-esophageal responses during retching and vomitus expulsion. The proximal gastric response allows gastroesophageal reflux, the lower pharyngeal response prevents supra-esophageal reflux, and both last the duration of the vomit process. The retrograde giant contraction empties the proximal digestive tract of noxious agents and supplies the stomach with fluids to neutralize the gastric acid which protect the esophagus from damage during expulsion. The retch mixes the gastric contents with acid neutralizer and gives momentum to the expelled bolus. During vomitus expulsion the esophagus is maximally stretched longitudinally which stiffens its wall to allow rapid transport as the suprahyoid muscles and diaphragmatic dome contract, and the hiatal fibers relax.

Biomechanical effects of esophageal elongation on the circumferential tension of the cervical esophagus in vivo.

Evidence obtained ex vivo suggests that physical elongation of the esophagus increases esophageal circumferential stress-strain ratio, but it is unknown whether this biomechanical effect alters esophageal function in vivo. We investigated the effects of physical or physiological elongation of the cervical esophagus on basal and active circumferential tension in vivo. The esophagus was elongated, using 29 decerebrate cats, either physically by distal physical extension of the esophagus or physiologically by stimulating the hypoglossal nerve, which activates laryngeal elevating muscles that elongate the esophagus. Hyoid, pharyngeal, and esophageal muscles were instrumented with electromyogram (EMG) electrodes and/or strain gauge force transducers. Esophageal intraluminal manometry was also recorded. We found that physical or physiological elongation of the cervical esophagus increased esophageal circumferential basal as well as active tension initiated by electrical stimulation of the pharyngo-esophageal nerve or the esophageal muscle directly, but did not increase esophageal intraluminal pressure or EMG activity. The esophageal circumferential response to the esophago-esophageal contractile reflex was increased by distal physical elongation, but not orad physiological elongation. We conclude that physical or physiological elongation of the esophagus significantly increases esophageal circumferential basal and active tension without muscle activation. We hypothesize that this effect is caused by an increase in esophageal stress-strain ratio by a biomechanical process, which increases circumferential wall stiffness. The increase in esophageal circumferential stiffness increases passive tension and the effectiveness of active tension. This increase in cervical esophageal circumferential stiffness may alter esophageal function.NEW & NOTEWORTHY Physical or physiological esophageal elongation increases esophageal circumferential active or passive tension by a biomechanical process, which causes a decrease in esophageal circumferential elasticity. This increased stiffness of the esophageal wall likely promotes esophageal bolus flow during various esophageal functions.

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.

Mechanisms of bradycardia in premature infants: Aerodigestive-cardiac regulatory-rhythm interactions.

OBJECTIVE: Eating difficulties coupled with cardiorespiratory spells delay acquisition of feeding milestones in convalescing neonates, and the mechanisms are unclear. Aims were to examine and compare the pharyngoesophageal-cardiorespiratory (PECR) response characteristics: (a) in control neonates and those with recurrent bradycardia spells; and (b) during pharyngeal stimulation when bradycardia occurs versus when no bradycardia occurs. METHODS: Preterm infants (N = 40, 27 ± 3 weeks gestation), underwent concurrent pharyngoesophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor to evaluate pharyngoesophageal motility, heart rate (HR), and respiration during graded abrupt pharyngeal sterile water stimuli. Infants with recurrent bradycardia (N = 28) and controls (N = 12) were evaluated at 38 (38-40) and 39 (38-40) weeks postmenstrual age, respectively. Comparisons were performed (a) between study and control groups; and (b) among HR responses of <80 BPM, 80-100 BPM, and >100 BPM. RESULTS: Overall, characteristics of PECR responses in infants with a history of recurrent bradycardia (vs. controls) did not differ (p > .05). However, when pharyngeal stimulus induced severe bradycardia (<80 BPM): prolonged respiratory rhythm change, increased pharyngeal activity, increased esophageal dysmotility (as evidenced by prolonged esophageal inhibition and motor activity), and prolonged lower esophageal sphincter relaxation were noted (all p < .05). CONCLUSIONS: In control infants and those with recurrent bradycardia, pharyngeal stimulation results in similar PECR response characteristics. However, when severe bradycardia occurs, PECR response characteristics are distinct. The mechanisms of severe bradycardia spells are related to abnormal prolongation of vagal inhibitory effects on cardiorespiratory rhythms in conjunction with prolonged esophageal inhibition and delays with terminal swallow.

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.

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.

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.

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.

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.

Mechanisms of airway responses to esophageal acidification in cats.

Acid in the esophagus causes airway constriction, tracheobronchial mucous secretion, and a decrease in tracheal mucociliary transport rate. This study was designed to investigate the neuropharmacological mechanisms controlling these responses. In chloralose-anesthetized cats (n = 72), we investigated the effects of vagotomy or atropine (100 µg·kg(-1)·30 min(-1) iv) on airway responses to esophageal infusion of 0.1 M PBS or 0.1 N HCl at 1 ml/min. We quantified 1) diameter of the bronchi, 2) tracheobronchial mucociliary transport rate, 3) tracheobronchial mucous secretion, and 4) mucous content of the tracheal epithelium and submucosa. We found that vagotomy or atropine blocked the airway constriction response but only atropine blocked the increase in mucous output and decrease in mucociliary transport rate caused by esophageal acidification. The mucous cells of the mucosa produced more Alcian blue- than periodic acid-Schiff (PAS)-stained mucosubstances, and the mucous cells of the submucosa produced more PAS- than Alcian blue-stained mucosubstances. Selective perfusion of the different segments of esophagus with HCl or PBS resulted in significantly greater production of PAS-stained mucus in the submucosa of the trachea adjacent to the HCl-perfused esophagus than in that adjacent to the PBS-perfused esophagus. In conclusion, airway constriction caused by esophageal acidification is mediated by a vagal cholinergic pathway, and the tracheobronchial transport response is mediated by cholinergic receptors. Acid perfusion of the esophagus selectively increases production of neutral mucosubstances of the apocrine glands by a local mechanism. We hypothesize that the airway responses to esophageal acid exposure are part of the innate, rather than acute emergency, airway defense system.

The Physiology of Eructation.

Eructation is composed of three independent phases: gas escape, upper barrier elimination, and gas transport phases. The gas escape phase is the gastro-LES inhibitory reflex that causes transient relaxation of the lower esophageal sphincter, which is activated by distension of stretch receptors of the proximal stomach. The upper barrier elimination phase is the transient relaxation of the upper esophageal sphincter along with airway protection. This phase is activated by stimulation of rapidly adapting mechanoreceptors of the esophageal mucosa. The gas transport phase is esophageal reverse peristalsis mediated by elementary reflexes, and it is theorized that this phase is activated by serosal rapidly adapting tension receptors. Alteration of the receptors which activate the upper barrier elimination phase of eructation by gastro-esophageal reflux of acid may in part contribute to the development of supra-esophageal reflux disease.

The Role of Central and Enteric Nervous Systems in the Control of the Retrograde Giant Contraction.

BACKGROUND/AIMS: The role of the enteric (ENS) and central (CNS) nervous systems in the control of the retrograde giant contraction (RGC) associated with vomiting is unknown. METHODS: The effects of myotomy or mesenteric nerve transection (MNT) on apomorphine-induced emesis were investigated in 18 chronically instrumented dogs. RESULTS: Neither surgery affected the RGC orad of the surgical site or the velocity of the RGC over the entire small intestine. Myotomy blocked the RGC for 17 ± 5 cm aborad of the myotomy, and the velocity of the RGC from 100 to 70 cm from the pylorus slowed (18.1 ± 3.0 to 9.0 ± 0.8 cm/sec) such that the RGC orad and aborad of the myotomy occurred simultaneously. After MNT, the RGC was unchanged up to 66 ± 6 cm from the pylorus, and the sequence of the RGC across the denervated intestine was unaltered. The velocity of the RGC from 100 to 70 cm from the pylorus increased from 12.8 ± 1.6 to 196 ± 116 cm/sec. After myotomy or MNT, the percent occurrence and magnitude of the RGC across the intestine 100 to 70 cm from the pylorus decreased. CONCLUSIONS: The CNS activates the RGC 10 to 20 cm aborad of its innervation of the intestine and controls the RGC sequence. On the other hand, the ENS plays a role in initiation and generation of the RGC.

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.

Mechanism of UES relaxation initiated by gastric air distension.

The aim of this study was to determine the mechanism of initiation of transient upper esophageal sphincter relaxation (TUESR) caused by gastric air distension. Cats (n = 31) were decerebrated, EMG electrodes were placed on the cricopharyngeus, a gastric fistula was formed, and a strain gauge was sewn on the lower esophageal sphincter (n = 8). Injection of air (114 ± 13 ml) in the stomach caused TUESR (n = 18) and transient lower esophageal sphincter relaxation (TLESR, n = 6), and this effect was not significantly (P > 0.05) affected by thoracotomy. Free air or bagged air (n = 6) activated TLESR, but only free air activated TUESR. Closure of the gastroesophageal junction blocked TUESR (9/9), but not TLESR (4/4), caused by air inflation of the stomach. Venting air from distal esophagus during air inflation of the stomach prevented TUESR (n = 12) but did not prevent air escape from the stomach to the esophagus (n = 4). Rapid injection of air on the esophageal mucosa always caused TUESR (9/9) but did not always (7/9) cause an increase in esophageal pressure. The time delay between the TUESR and the rapid air pulse was significantly more variable (P < 0.05) than the time delay between the rapid air pulse and the rise in esophageal pressure. We concluded that the TUESR caused by gastric air distension is dependent on air escape from the stomach, which stimulates receptors in the esophagus, but is not dependent on distension of the stomach or esophagus, or the TLESR. Therefore, the TUESR caused by gastric air distension is initiated by stimulation of receptors in the esophageal mucosa.

Role of peripheral reflexes in the initiation of the esophageal phase of swallowing.

The aim of this study was to determine the role of peripheral reflexes in initiation of the esophageal phase of swallowing. In 10 decerebrate cats, we recorded electromyographic responses from the pharynx, larynx, and esophagus and manometric data from the esophagus. Water (1-5 ml) was injected into the nasopharynx to stimulate swallowing, and the timing of the pharyngeal and esophageal phases of swallowing was quantified. The effects of transection or stimulation of nerves innervating the esophagus on swallowing and esophageal motility were tested. We found that the percent occurrence of the esophageal phase was significantly related to the bolus size. While the time delays between the pharyngeal and esophageal phases of swallowing were not related to the bolus size, they were significantly more variable than the time delays between activation of muscles within the pharyngeal phase. Transection of the sensory innervation of the proximal cervical esophagus blocked or significantly inhibited activation of the esophageal phase in the proximal cervical esophagus. Peripheral electrical stimulation of the pharyngoesophageal nerve activated the proximal cervical esophagus, peripheral electrical stimulation of the vagus nerve activated the distal cervical esophagus, and peripheral electrical stimulation the superior laryngeal nerve (SLN) had no effect on the esophagus. Centripetal electrical stimulation of the SLN activated the cervical component of the esophageal phase of swallowing before initiation of the pharyngeal phase. Therefore, we concluded that initiation of the esophageal phase of swallowing depends on feedback from peripheral reflexes acting through the SLN, rather than a central program.

Digestive and respiratory tract motor responses associated with eructation.

We studied the digestive and respiratory tract motor responses in 10 chronically instrumented dogs during eructation activated after feeding. Muscles were recorded from the cervical area, thorax, and abdomen. The striated muscles were recorded using EMG and the smooth muscles using strain gauges. We found eructation in three distinct functional phases that were composed of different sets of motor responses: gas escape, barrier elimination, and gas transport. The gas escape phase, activated by gastric distension, consists of relaxation of the lower esophageal sphincter and diaphragmatic hiatus and contraction of the longitudinal muscle of the thoracic esophagus and rectus abdominis. All these motor events promote gas escape from the stomach. The barrier elimination phase, probably activated by rapid gas distension of the thoracic esophagus, consists of relaxation of the pharyngeal constrictors and excitation of dorsal and ventral upper esophageal sphincter distracting muscles, as well as rapid contraction of the diaphragmatic dome fibers. These motor events allow esophagopharyngeal air movement by promoting retrograde airflow and opening of the upper esophageal sphincter. The transport phase, possibly activated secondary to diaphragmatic contraction, consists of a retrograde contraction of the striated muscle esophagus that transports the air from the thoracic esophagus to the pharynx. We hypothesize that the esophageal reverse peristalsis is mediated by elementary reflexes, rather than a coordinated peristaltic response like secondary peristalsis. The phases of eructation can be activated independently of one another or in a different manner to participate in physiological events other than eructation that cause gastroesophageal or esophagogastric reflux.

Neuronal plasticity in the cingulate cortex of rats following esophageal acid exposure in early life.

BACKGROUND & AIMS: The cingulate cortex has been reported to be involved in processing pain of esophageal origin. However, little is known about molecular changes and cortical activation that arise from early-life esophageal acid reflux. Excitatory neurotransmission via activation of the N-methyl-d-aspartate (NMDA) receptor and its interaction with postsynaptic density protein 95 (PSD-95) at the synapse appear to mediate neuronal development and plasticity. We investigated the effect of early-life esophageal acid exposure on NMDA receptor subunits and PSD-95 expression in the developing cingulate cortex. METHODS: We assessed NMDA receptor subunits and PSD-95 protein expression in rostral cingulate cortex (rCC) tissues of rats exposed to esophageal acid or saline (control), either during postnatal day (P) 7 to 14 and/or acutely at adult stage (P60) using immunoblot and immunoprecipitation analyses. RESULTS: Compared with controls, acid exposure from P7 to P14 significantly increased expression of NR1, NR2A, and PSD-95, measured 6 weeks after exposure. However, acute exposure at P60 caused a transient increase in expression of NMDA receptor subunits. These molecular changes were more robust in animals exposed to acid neonatally and rechallenged, acutely, at P60. Esophageal acid exposure induced calcium calmodulin kinase II-mediated phosphorylation of the subunit NR2B at Ser1303. CONCLUSIONS: Esophageal acid exposure during early stages of life has long-term effects as a result of phosphorylation of the NMDA receptor and overexpression in the rCC. This molecular alteration in the rCC might mediate sensitization of patients with acid-induced esophageal disorders.