Mechanisms of reflexes induced by esophageal distension

We investigated the mechanisms of esophageal distension-induced reflexes in decerebrate cats. Slow air esophageal distension activated esophago-upper esophageal sphincter (UES) contractile reflex (EUCR) and secondary peristalsis (2P). Rapid air distension activated esophago-UES relaxation reflex (EURR), esophago-glottal closure reflex (EGCR), esophago-hyoid distraction reflex (EHDR), and esophago-esophagus contraction reflex (EECR). Longitudinal esophageal stretch did not activate these reflexes. Magnitude and timing of EUCR were related to 2P but not injected air volume. Cervical esophagus transection did not affect the threshold of any reflex. Bolus diversion prevented swallow-related esophageal peristalsis. Lidocaine or capsaicin esophageal perfusion, esophageal mucosal layer removal, or intravenous baclofen blocked or inhibited EURR, EGCR, EHDR, and EECR but not EUCR or 2P. Thoracic vagotomy blocked all reflexes. These six reflexes can be activated by esophageal distension, and they occur in two sets depending on inflation rate rather than volume. EUCR was independent of 2P, but 2P activated EUCR; therefore, EUCR may help prevent reflux during peristalsis. All esophageal peristalsis may be secondary to esophageal stimulation in the cat. EURR, EHDR, EGCR, and EECR may contribute to belching and are probably mediated by capsaicin-sensitive, rapidly adapting mucosal mechanoreceptors. GABA-B receptors also inhibit these reflexes. EUCR and 2P are probably mediated by slowly adapting muscular mechanoreceptors. All six reflexes are mediated by vagal afferent fibers.     

A novel pattern of longitudinal muscle contraction with subthreshold pharyngeal stimulus: a possible mechanism of lower esophageal sphincter relaxation

A subthreshold pharyngeal stimulus induces lower esophageal sphincter (LES) relaxation and inhibits progression of ongoing peristaltic contraction in the esophagus. Recent studies show that longitudinal muscle contraction of the esophagus may play a role in LES relaxation. Our goal was to determine whether a subthreshold pharyngeal stimulus induces contraction of the longitudinal muscle of the esophagus and to determine the nature of this contraction. Studies were conducted in 16 healthy subjects. High resolution manometry (HRM) recorded pressures, and high frequency intraluminal ultrasound (HFIUS) images recorded longitudinal muscle contraction at various locations in the esophagus. Subthreshold pharyngeal stimulation was induced by injection of minute amounts of water in the pharynx. A subthreshold pharyngeal stimulus induced strong contraction and caudal descent of the upper esophageal sphincter (UES) along with relaxation of the LES. HFIUS identified longitudinal muscle contraction of the proximal (3-5 cm below the UES) but not the distal esophagus. Pharyngeal stimulus, following a dry swallow, blocked the progression of dry swallow-induced peristalsis; this was also associated with UES contraction and descent along with the contraction of longitudinal muscle of the proximal esophagus. We identify a unique pattern of longitudinal muscle contraction of the proximal esophagus in response to subthreshold pharyngeal stimulus, which we propose may be responsible for relaxation of the distal esophagus and LES through the stretch sensitive activation of myenteric inhibitory motor neurons.     

Disruption of primary and secondary esophageal peristalsis by afferent stimulation

Recent studies have shown that afferent signals originating from the pharynx inhibit progression of primary esophageal peristalsis. Our aim was to further elucidate the effect of esophageal and pharyngeal afferent stimulation on primary and secondary esophageal peristalsis. We studied the effect of esophageal air distension and pharyngeal water stimulation on progression of primary and secondary peristalsis in nine healthy volunteers aged 27 +/- 2 yr (4 men, 5 women). At a threshold volume, rapid injection of water into the pharynx, directed posteriorly, resulted in complete halt of the progressing secondary and primary esophageal peristalses in both the proximal and distal esophagus. The threshold volume of injected water for inducing inhibition was similar for secondary (0.6 +/- 0.2 ml) and primary (0.5 +/- 0.1 ml) esophageal peristalsis. Progression of primary peristalsis induced by a dry swallow and secondary peristalsis induced by intraesophageal air distension were completely inhibited by intraesophageal injection of 15 +/- 2 ml of air in 70% and 75% of the trials, respectively. We conclude that afferent signals induced by esophageal air distension and pharyngeal water stimulation inhibit propagation of both primary and secondary esophageal peristalsis, suggesting a shared neural control mechanism for these types of peristalsis.     

Differential relaxation and contractile responses of the human upper esophageal sphincter mediated by interplay of mucosal and deep mechanoreceptor activation

BACKGROUND AND AIMS: the neural mechanisms of distension-induced esophagoupper esophageal sphincter (UES) reflexes have not been explored in humans. We investigated the modulation of these reflexes by mucosal anesthesia, acid exposure, and GABA(B) receptor activation. In 55 healthy human subjects, UES responses to rapid esophageal air insufflation and slow balloon distension were examined before and after pretreatment with 15 ml of topical esophageal lidocaine, esophageal HCl infusion, and baclofen 40 mg given orally. In response to rapid esophageal distension, UES can variably relax or contract. Following a mucosal blockade by topical lidocaine, the likelihood of a UES relaxation response was reduced by 11% (P < 0.01) and the likelihood of a UES contractile response was increased by 14% (P < 0.001) without alteration in the overall UES response rate. The UES contractile response to rapid esophageal air insufflation was also increased by 8% (P < 0.05) following sensitization by prior mucosal acid exposure. The UES contractile response, elicited by balloon distension, was regionally dependent (P < 0.05) (more frequent and of higher amplitude with proximal esophageal distension), and the response was attenuated by topical lidocaine (P < 0.05). Baclofen (40 mg po) had no effect on these UES reflexes. Abrupt gaseous esophageal distension activates simultaneously both excitatory and inhibitory pathways to the UES. Partial blockade of the mucosal mechanosensitive receptors permits an enhanced UES contractile response mediated by deeper esophageal mechanoreceptors. Activation of acid-sensitive esophageal mucosal chemoreceptors upregulates the UES contractile response, suggestive of a protective mechanism.     

Adult human upper esophageal sphincter contains specialized muscle fibers expressing unusual myosin heavy chain isoforms.

The functional upper esophageal sphincter (UES) is composed of the cricopharyngeus muscle (CP), the most inferior part of the inferior pharyngeal constrictor (iIPC), and the upper esophagus (UE). This sphincter is collapsed and exhibits sustained muscle activity in the resting state; it only relaxes and opens during swallowing, vomiting, and belching. The tonic contractile properties of the UES suggest that the skeletal muscle fibers in this sphincter differ from those in the limb and trunk muscles. In this study, myosin heavy chain (MHC) composition in the adult human UES muscles obtained from autopsies was investigated using immunocytochemical and immunoblotting techniques. Results showed that the adult human UES muscle fibers expressed unusual MHC isoforms such as slow-tonic (MHC-ton), alpha-cardiac (MHC-alpha), neonatal (MHC-neo), and embryonic (MHC-emb), which coexisted with the major MHCs (i.e., MHCI, IIa, and IIx). MHC-ton and MHC-alpha were coexpressed predominantly with slow-type I MHC isoform, whereas MHC-neo and MHC-emb coexisted mainly with fast-type IIa MHC. A slow inner layer (SIL) and a fast outer layer (FOL) in the iIPC and CP were identified immunocytochemically. MHC-ton- and MHC-alpha-containing fibers were concentrated mainly in the SIL, whereas MHC-neo- and MHC-emb-containing fibers were distributed primarily to the FOL. Identification of the specialized muscle fibers and their distribution patterns in the adult human UES is valuable for a better understanding of the physiological and pathophysiological behaviors of the sphincter.     

Central regulation of the pharyngeal and upper esophageal reflexes during swallowing in the Japanese eel

We investigated the regulation of the pharyngeal and upper esophageal reflexes during swallowing in eel. By retrograde tracing from the muscles, the motoneurons of the upper esophageal sphincter (UES) were located caudally within the mid-region of the glossopharyngeal-vagal motor complex (mGVC). In contrast, the motoneurons innervating the pharyngeal wall were localized medially within mGVC. Sensory pharyngeal fibers in the vagal nerve terminated in the caudal region of the viscerosensory column (cVSC). Using the isolated brain, we recorded 51 spontaneously active neurons within mGVC. These neurons could be divided into rhythmically (n = 8) and continuously (n = 43) firing units. The rhythmically firing neurons seemed to be restricted medially, whereas the continuously firing neurons were found caudally within mGVC. The rhythmically firing neurons were activated by the stimulation of the cVSC. In contrast, the stimulation of the cVSC inhibited firing of most, but not all the continuously firing neurons. The inhibitory effect was blocked by prazosin in 17 out of 38 neurons. Yohimbine also blocked the cVSC-induced inhibition in five of prazosin-sensitive neurons. We suggest that the neurons in cVSC inhibit the continuously firing motoneurons to relax the UES and stimulate the rhythmically firing neurons to constrict the pharynx simultaneously.     

Swallowing reflex and brain stem neurons activated by superior laryngeal nerve stimulation in the mouse

The purpose of the present study was to identify vagal subnuclei that participate in reflex swallowing in response to electrical stimulation of the left superior laryngeal nerve (SLN). SLN stimulation at 10 Hz evoked primary peristalsis, including oropharyngeal and esophageal peristalsis, and LES relaxation. It also induced c-fos expression in interneurons in the interstitial (SolI), intermediate (SolIM), central (SolCe), dorsomedial (SolDM) and commissural (SolC) solitary subnuclei. Neurons in parvicellular reticular nucleus (PCRt) and area postrema (AP) and motoneurons in the semicompact (NAsc), loose (NAl), and compact (NAc) formations of the nucleus ambiguus and both rostral (DMVr) and caudal (DMVc) parts of the dorsal motor nucleus of vagus were also activated. The activated neurons represent all neurons concerned with afferent SLN-mediated reflexes, including the swallowing-related neurons. SLN stimulation at 5 Hz elicited oropharyngeal and LES but not esophageal responses and evoked c-fos expression in neurons in SolI, SolIM, SolDM, PCRt, AP, NAsc, NAl, and DMVc but not in SolCe, NAc, or DMVr. These data are consistent with the role of SolI, SolIM, SolDM, NAsc, NAl, and DMVc circuit in oropharyngeal peristalsis and LES relaxation and SolCe, NAc, DMVc, and DMVr in esophageal peristalsis and LES responses.     

Assessment of intraluminal impedance for the detection of pharyngeal bolus flow during swallowing in healthy adults

Intraluminal impedance, a nonradiological method for assessing bolus flow within the gut, may be suitable for investigating pharyngeal disorders. This study evaluated an impedance technique for the detection of pharyngeal bolus flow during swallowing. Patterns of pharyngoesophageal pressure and impedance were simultaneously recorded with videofluoroscopy in 10 healthy volunteers during swallowing of liquid, semisolid, and solid boluses. The timing of bolus head and tail passage recorded by fluoroscopy was correlated with the timing of impedance drop and recovery at each recording site. Bolus swallowing produced a drop in impedance from baseline followed by a recovery to at least 50% of baseline. The timing of the pharyngeal and esophageal impedance drop correlated with the timing of the arrival of the bolus head. In the pharynx, the timing of impedance recovery was delayed relative to the timing of clearance of the bolus tail. In contrast, in the upper esophageal sphincter (UES) and proximal esophagus, the timing of impedance recovery correlated well with the timing of clearance of the bolus tail. Impedance-based estimates of pharyngoesophageal bolus clearance time correlated with true pharyngoesophageal bolus clearance time. Patterns of intraluminal impedance recorded in the pharynx during bolus swallowing are therefore more complex than those in the esophagus. During swallowing, mucosal contact between the tongue base and posterior pharyngeal wall prolongs the duration of pharyngeal impedance drop, leading to overestimation of bolus tail timing. Therefore, we conclude that intraluminal impedance measurement does not accurately reflect the bolus transit in the pharynx but does accurately reflect bolus transit across the UES and below.     

Patterns of esophageal inhibition during swallowing,pharyngeal stimulation,and transient LES relaxation. Lower esophageal sphincter

Lower esophageal sphincter (LES) relaxation and esophageal body inhibition co-occur during esophageal peristalsis but not necessarily during pharyngeal stimulation or transient LES relaxation (tLESR). This study examined these relationships and the impact on reflux. Nine young volunteers were studied. An artificial high-pressure zone (HPZ) was established, and pH was recorded 8 and 5 cm proximal to the LES. Pharyngeal stimulation was by water injection and gastric distension with liquid or gas. Peristalsis, pharyngeal stimulation, and spontaneous events were recorded. Swallowing relaxed the LES in 100% of trials (the HPZ in 80%) and caused no reflux. Pharyngeal stimulation relaxed the LES in two-thirds of trials, had no effect on the HPZ, and caused no reflux. Gastric distension was associated with 117 tLESRs, 48% with acid reflux, and 32% with gas reflux; there was no effect on the HPZ. We conclude that LES relaxation is a necessary but not sufficient condition for reflux. LES relaxation and esophageal body inhibition are independent events that may be concurrent (swallowing) or dissociated (tLESR).     

Absence of a deglutitive inhibition equivalent with secondary peristalsis

This study aimed to determine the interactions between closely paired swallow-induced primary peristalsis (PP) and air injection-induced secondary peristalsis (SP). Ten subjects (7 men, 18-42 yr) were studied using a catheter, including two sleeves (upper and lower esophageal sphincters), a midesophageal infusion port, and seven esophageal and two pharyngeal recording sites. Ten iterations of PP and SP were induced by 5-ml water swallows and 20-ml intraesophageal air injections, respectively. Thereafter, the interactions between PP and SP, separated by 1- to 12-s intervals, were studied in all four possible sequences: paired swallows, swallow preceded by air injection, air injection preceded by swallow, and paired air injections. Tracings were analyzed for lower esophageal sphincter relaxation, presence and integrity of peristalsis, and event interaction. Eight subjects with success rates of both >/=90% PP and >/=80% SP were analyzed (PP 97 +/- 2%, SP 90 +/- 3%). During paired PP interactions and SP followed by PP, the first sequence was inhibited by the second with intervals < 4-6 s. However, no inhibition of the first peristaltic sequence was found in either PP followed by SP trials or SP followed by air injection. In contrast to swallowing or proximal esophageal distention, air injection into the lumen of the midesophagus does not inhibit an ongoing peristaltic event. Being that the elicitation of SP in the smooth muscle esophagus is intramurally mediated, this suggests that deglutitive inhibition is a centrally mediated phenomenon rather than an intrinsic property of peristalsis.     

Crural diaphragm inhibition during esophageal distension correlates with contraction of the esophageal longitudinal muscle in cats

Esophageal distension causes simultaneous relaxation of the lower esophageal sphincter (LES) and crural diaphragm. The mechanism of crural diaphragm relaxation during esophageal distension is not well understood. We studied the motion of crural and costal diaphragm along with the motion of the distal esophagus during esophageal distension-induced relaxation of the LES and crural diaphragm. Wire electrodes were surgically implanted into the crural and costal diaphragm in five cats. In two additional cats, radiopaque markers were also sutured into the outer wall of the distal esophagus to monitor esophageal shortening. Under light anesthesia, animals were placed on an X-ray fluoroscope to monitor the motion of the diaphragm and the distal esophagus by tracking the radiopaque markers. Crural and costal diaphragm electromyograms (EMGs) were recorded along with the esophageal, LES, and gastric pressures. A 2-cm balloon placed 5 cm above the LES was used for esophageal distension. Effects of baclofen, a GABA(B) agonist, were also studied. Esophageal distension induced LES relaxation and selective inhibition of the crural diaphragm EMG. The crural diaphragm moved in a craniocaudal direction with expiration and inspiration, respectively. Esophageal distension-induced inhibition of the crural EMG was associated with sustained cranial motion of the crural diaphragm and esophagus. Baclofen blocked distension-induced LES relaxation and crural diaphragm EMG inhibition along with the cranial motion of the crural diaphragm and the distal esophagus. There is a close temporal correlation between esophageal distension-mediated LES relaxation and crural diaphragm inhibition with the sustained cranial motion of the crural diaphragm. Stretch caused by the longitudinal muscle contraction of the esophagus during distension of the esophagus may be important in causing LES relaxation and crural diaphragm inhibition.     

Upper esophageal sphincter function during gastroesophageal reflux events revisited

Upper esophageal sphincter (UES) function during gastroesophageal reflux events is not completely elucidated because previous studies addressing this issue yielded conflicting results. We reexamined the UES pressure response to intraluminal esophageal pressure and pH changes induced by reflux events. We studied 14 healthy, asymptomatic volunteers (age 49 +/- 6 yr) and 7 gastroesophageal reflux disease patients (age 48 +/- 5 yr). UES pressure, intraesophageal pressure, and pH were monitored at the distal, middle, and proximal esophagus concurrently in the supine position 1 h before and 2 h after a 1,000-calorie meal. A total of 321 reflux events were identified by the development of abrupt reflux-induced intraesophageal pressure increase (IPI); 285 events occurred in patients and 36 in control subjects. In control subjects 33 of 36 and in patients 252 of 285 IPI events were associated with a pH drop. Among patients and control subjects, 99% and 100%, respectively, of all IPI events irrespective of pH drop were associated with abrupt increase in UES pressure (34 +/- 2 and 27 +/- 6 mmHg, respectively). The average percentage of maximum UES pressure increase over prereflux values ranged between 66% and 96% (control subjects) and 34% and 122% (patients). IPIs induced by both acidic and nonacidic reflux events evoke strong UES contractile responses.     

Biomechanics of failed deglutitive upper esophageal sphincter relaxation in neurogenic dysphagia

Our aims were to examine the etiology and biomechanical properties of the nonrelaxing upper esophageal sphincter (UES) and the relationship between UES opening and failed relaxation. We examined the relationships among swallowed bolus volume, intrabolus pressure, sagittal UES diameter, the pharyngeal swallow response, and geniohyoid shortening in 18 patients with failed UES relaxation, 23 healthy aged controls, and 15 with Zenker's diverticulum. Etiology of failed UES relaxation was 56% medullary disease, 33% Parkinson's or extrapyramidal disease; and 11% idiopathic. Extent of UES opening ranged from absent to normal and correlated with preservation of the pharyngeal swallow response (P = 0.012) and geniohyoid shortening (P = 0.046). Intrabolus pressure was significantly greater compared with aged controls (P < 0.001) or Zenker's diverticulum (P < 0.001). The bolus volume-dependent increase in intrabolus pressure evident in controls was not observed in failed UES relaxation. The nonrelaxing UES therefore displays a constant loss of sphincter compliance throughout the full, and potentially normal, range of expansion during opening. Adequacy of UES opening is influenced by the degree of preservation of the pharyngeal swallow response and hyolaryngeal traction. In contrast, the stenotic UES displays a static loss of compliance, only apparent once the limit of sphincter expansion is reached.     

Oesophageal peristalsis in the cat: the role of central innervation assessed by transient vagal blockade

Studies were performed on five cats to assess the role of extrinsic vagal innervation in the control of peristalsis in the smooth muscle oesophagus. Transient vagal nerve blockade was accomplished by cooling the cervical vagosympathetic nerve trunks previously isolated in skin loops on each side of the neck. Peristalsis throughout the body of the oesophagus was monitored using a continuously perfused multilumen manometry tube. Striated and smooth muscle portions of the esophagus were delineated by abolishing smooth muscle activity with atropine. Secondary peristalsis was assessed by intra-oesophageal balloon distension studies. The threshold volume for balloon-induced secondary peristalsis was lower in the smooth muscle oesophagus. Unilateral vagal blockade reduced the incidence of primary and secondary peristalsis in the striated muscle oesophagus but not in the smooth muscle oesophagus. Bilateral vagal nerve blockade abolished primary swallow-induced peristalsis and secondary peristalsis in both the smooth and striated muscle cat oesophagus. Administration of cholinergic agents or adrenergic blocking agents failed to restore secondary peristalsis in the smooth muscle oesophagus during vagal cooling. We conclude that connections to the central nervous system via the vagal nerve trunks are required for normal secondary as well as primary peristalsis in both the smooth and striated muscle portions of the cat oesophagus.     

Evidence for a peripheral mechanism of esophagocrural diaphragm inhibitory reflex in cats

The esophagogastric junction (EGJ) is guarded by two sphincters, a smooth muscle lower esophageal sphincter (LES) and a skeletal muscle crural diaphragm. These two sphincters relax simultaneously under certain physiological conditions, i.e., swallowing, belching, vomiting, transient LES relaxation, and esophageal distension. Esophageal distension-induced crural diaphragm relaxation is mediated through vagal afferents that are thought to exert inhibitory influence on the central mechanism (brain stem) of crural diaphragm contraction. We conducted studies in 10 cats to determine whether a mechanism of crural diaphragm relaxation was located at the level of the neuromuscular junction and/or muscle. Stimulation of the crural diaphragm neuromuscular junction through 1) the electrodes implanted in the muscle and 2) the bilateral phrenic nerve resulted in an increase in EGJ pressure. Nicotinic receptor blockade (pancuronium, 0.2 mg/kg) abolished the EGJ pressure increase caused by electrical stimulation of the neuromuscular junction. Esophageal distension and bolus-induced secondary esophageal peristalsis caused relaxation of the EGJ during the stimulation of the neuromuscular junction. Bilateral phrenicotomy and vagotomy had no influence on this relaxation. These data suggest the existence of a peripheral mechanism of crural diaphragm inhibition. This peripheral inhibitory mechanism may reside at the level of either the neuromuscular junction or the skeletal muscle.     

Upper esophageal sphincter impedance as a marker of sphincter opening diameter

The measurement of the physical extent of opening of the upper esophageal sphincter (UES) during bolus swallowing has to date relied on videofluoroscopy. Theoretically luminal impedance measured during bolus flow should be influenced by luminal diameter. In this study, we measured the UES nadir impedance (lowest value of impedance) during bolus swallowing and assessed it as a potential correlate of UES diameter that can be determined nonradiologically. In 40 patients with dysphagia, bolus swallowing of liquids, semisolids, and solids was recorded with manometry, impedance, and videofluoroscopy. During swallows, the UES opening diameter (in the lateral fluoroscopic view) was measured and compared with automated impedance manometry (AIM)-derived swallow function variables and UES nadir impedance as well as high-resolution manometry-derived UES relaxation pressure variables. Of all measured variables, UES nadir impedance was the most strongly correlated with UES opening diameter. Narrower diameter correlated with higher impedance (r = -0.478, P < 0.001). Patients with <10 mm, 10-14 mm (normal), and ≥ 15 mm UES diameter had average UES nadir impedances of 498 ± 39 Ohms, 369 ± 31 Ohms, and 293 ± 17 Ohms, respectively (ANOVA P = 0.005). A higher swallow risk index, indicative of poor pharyngeal swallow function, was associated with narrower UES diameter and higher UES nadir impedance during swallowing. In contrast, UES relaxation pressure variables were not significantly altered in relation to UES diameter. We concluded that the UES nadir impedance correlates with opening diameter of the UES during bolus flow. This variable, when combined with other pharyngeal AIM analysis variables, may allow characterization of the pathophysiology of swallowing dysfunction.     

Catecholaminergic neurons in rat dorsal motor nucleus of vagus project selectively to gastric corpus

Nitric oxide synthase-immunoreactive (NOS-IR) neurons in the rat caudal dorsal motor nucleus of the vagus (DMV) project selectively to the gastric fundus and may be involved in vagal reflexes controlling gastric distension. This study aimed to identify the gastric projections of tyrosine hydroxylase-immunoreactive (TH-IR) DMV neurons, whether such neurons colocalize NOS-IR, and if they are activated after esophageal distension. Gastric-projecting neurons were identified after injection of retrograde tracers into the muscle wall of the gastric fundus, corpus, or antrum/pylorus before removal and processing of the brain stems for TH- and NOS-IR. A significantly higher proportion of corpus- compared with fundus- and antrum/pylorus-projecting neurons were TH-IR (14% compared with 4% and 2%, respectively, P < 0.05). Colocalization of NOS- and TH-IR was never observed in gastric-projecting neurons. In rats tested for c-Fos activation after intermittent esophageal balloon distension, no colocalization with TH-IR was observed in DMV neurons. These findings suggest that TH-IR neurons in the caudal DMV project mainly to the gastric corpus, constitute a subpopulation distinct from that of nitrergic vagal neurons, and are not activated on esophageal distension.     

Specificity of esophageal electrode recordings of posterior cricoarytenoid muscle activity

Esophageal electrodes have been used for recording the electromyographic (EMG) activity of the posterior cricoarytenoid muscle (PCA). To determine the specificity of this EMG technique, esophageal electrode recordings were compared with intramuscular recordings in eight anesthetized mongrel dogs. Intramuscular wire electrodes were placed in the right and left PCA, and the esophageal electrode was introduced through the nose or mouth and advanced into the upper esophagus. On direct visualization of the upper airway, the unshielded catheter electrode entered the esophagus on the right or left side. Cold block of the recurrent laryngeal nerve (RLN) ipsilateral to the esophageal electrode was associated with a marked decrease in recorded activity, whereas cold block of the contralateral RLN resulted only in a small reduction in activity. After supplemental doses of anesthesia were administered, bilateral RLN cold block essentially abolished the activity recorded with the intramuscular electrodes as well as that recorded with the esophageal electrode. Before supplemental doses of anesthesia were given, especially after vagotomy, the esophageal electrode, and in some cases the intramuscular electrodes, recorded phasic inspiratory activity not originating from the PCA. Therefore, one should be cautious in interpreting the activity recorded from esophageal electrodes as originating from the PCA, especially in conditions associated with increased respiratory efforts.     

Quantifying esophageal peristalsis with high-resolution manometry: a study of 75 asymptomatic volunteers

The vastly enhanced spatial resolution of high-resolution manometry (HRM) makes it possible to simultaneous monitor contractile activity over the entire length of the esophagus. The aim of this investigation was to define the essential features of esophageal peristalsis in novel HRM paradigms and establish their normative values. Ten 5-ml water swallows were recorded in each of 75 asymptomatic controls with a solid-state manometric assembly incorporating 36 circumferential sensors spaced at 1-cm intervals positioned to record from the hypopharynx to the stomach. The data set was then subjected to intensive computational analysis to distill out the essential characteristics of normal peristalsis. Esophageal peristalsis was conceptualized in terms of a proximal contraction, a distal contraction, and a transition zone separating the two. Each contractile segment was quantified in length and then normalized among subjects to summarize focal fluctuation of contractile amplitude and propagation velocity. Furthermore, the temporal and spatial characteristics of the transition zone separating the proximal and distal contraction were quantified. For each paradigm, graphics were developed, establishing median values along with the 5th to 95th percentile range of observed variation. In addition, the synchronization between peristalsis and esophagogastric junction relaxation was analyzed using a novel concept of the outflow permissive pressure gradient. We performed a detailed analysis of esophageal peristalsis aimed at quantifying its essential features and, in so doing, devised new paradigms for the quantification of peristaltic function that will hopefully optimize the utility of HRM in clinical and investigative studies.     

Esophageal-gastric relaxation reflex in rat: dual control of peripheral nitrergic and cholinergic transmission

It has long been known that the esophageal distension produced by swallowing elicits a powerful proximal gastric relaxation. Gastroinhibitory control by the esophagus involves neural pathways from esophageal distension-sensitive neurons in the nucleus tractus solitarius centralis (cNTS) with connections to virtually all levels of the dorsal motor nucleus of the vagus (DMV). We have shown recently that cNTS responses are excitatory and primarily involve tyrosine hydroxylase-immunoreactive cells, whereas the DMV response involves both an alpha1 excitatory and an alpha2 inhibitory response. In the present study, using an esophageal balloon distension to evoke gastric relaxation (esophageal-gastric reflex, EGR), we investigated the peripheral pharmacological basis responsible for this reflex. Systemic administration of atropine methyl nitrate reduced the amplitude of the gastric relaxation to 52.0+/-4.4% of the original EGR, whereas NG-nitro-L-arginine methyl ester (L-NAME) reduced it to 26.3+/-7.2% of the original EGR. Concomitant administration of atropine methyl nitrate and L-NAME reduced the amplitude of the gastric relaxation to 4.0+/-2.5% of control. This reduction in the amplitude of induced EGR is quite comparable (4.3+/-2.6%) to that seen when the animal was pretreated with the nicotinic ganglionic blocker hexamethonium. In the presence of bethanechol, the amplitude of the esophageal distension-induced gastric relaxation was increased to 177.0+/-10.0% of control; administration of L-NAME reduced this amplitude to 19.9+/-9.5%. Our data provide a clear demonstration that the gastroinhibitory control by the esophagus is mediated via a dual vagal innervation consisting of inhibitory nitrergic and excitatory cholinergic transmission.