Transient Relaxation Research Articles

Enhanced nicotinic receptor mediated relaxations in gastroesophageal muscle fibers from Barrett's esophagus patients

Increased nicotinic receptor mediated relaxation in the gastroesophageal antireflux barrier may be involved in the pathophysiology of reflux. This study is designed to determine whether the defects we previously identified in gastroesophageal reflux disease patients in- vivo are due to abnormalities of the gastric sling, gastric clasp, or lower esophageal circular (LEC) muscle fibers. Muscle strips from whole stomachs and esophagi were obtained from 16 normal donors and 15 donors with histologically proven Barrett's esophagus. Contractile and relaxant responses of gastric sling, gastric clasp, or LEC fibers were determined to increasing concentrations of carbachol and to nicotine after inducing maximal contraction to bethanechol. Muscarinic receptor density was measured using subtype selective immunoprecipitation. Barrett's esophagus gastric sling and LEC fibers have decreased carbachol-induced contractions. Barrett's esophagus sling fibers have decreased M2 -muscarinic receptors and LEC fibers have decreased M3 receptors. Relaxations of all three fiber types are greater in Barrett's esophagus specimens to both high carbachol concentrations and to nicotine following bethanechol precontraction. The maximal response to bethanechol is greater in Barrett esophagus sling and LEC fibers. The increased contractile response to bethanechol in Barrett's specimens indicates that the defect is likely not due to the smooth muscle itself. The enhanced nicotinic receptor mediated response may be involved in greater relaxation of the muscles within the high-pressure zone of the gastroesophageal junction during transient lower esophageal sphincter relaxations and during deglutitive inhibition and may be involved in the pathophysiology of gastroesophageal reflux disease.

Dysmotility and reflux disease

In the last decade, with the advent of new oesophageal testing [i.e. 24-h impedance-pH monitoring, combined impedance-manometry, high-resolution manometry (HRM)], relevant progress in understanding the mechanisms contributing to the development of gastro-oesophageal reflux disease (GORD) has been made, allowing a better management of patients with this disorder. The aim of our review is to report the state-of-the-art about oesophageal motor disorders in patients with reflux disease and to stimulate new research in this field. Hypotensive lower oesophageal sphincter (LOS), transient LOS relaxations, impairment of oesophagogastric junction including hiatal hernia, oesophageal bolus transit abnormalities and presence of ineffective oesophageal motility have been strongly implicated in GORD development. In particular, the majority of recent studies carried out with HRM and impedance-pH testing reported that these motor abnormalities are increasingly prevalent with increasing severity of GORD, from nonerosive reflux disease and erosive oesophagitis to Barrett's oesophagus. Defining and characterizing oesophageal dysmotility in patients with reflux disease is of maximum importance in order to properly diagnose these patients and to treat them with the best management of care. New studies are needed in order to better understand the physiomechanic basis of oesophageal dysmotility in GORD patients.

Gut Motility Alterations in Neonates and Young Infants

C olic usually affects babies in the first few weeks of their lives and persists for about 4 months. Crying can be intense and furious and it may last for several hours per day for several weeks. Although crying can occur at any time, it is usually worse in the late afternoon and evening, and occasionally affects the baby’s sleep. Infantile colic is not considered a disease, fulfilling instead criteria for a functional disorder. Research shows that babies with colic continue to eat and gain weight appropriately, despite the crying (1). The main risk for these babies relates to the stress and anxiety that the condition creates at home, especially when it affects the first child. The cause of colic is not known. Painful flatus may contribute to colic, but there is little evidence to prove that it is linked to digestive problems (2). Another theory is that while the digestive system is maturing, some babies are more sensitive to substances such as lactose ingested through breast-feeding and formula milk; however, evidence to support this hypothesis also is limited. Other possible causes relate to the baby’s behavior and temperament. Among the gastrointestinal (GI) factors, we focus on non-nutritive pathophysiology such as the relation of colic to gastroesophageal reflux (GER), GI motility disorders, the role of gut hormones, and intestinal microflora.

Baclofen for the Treatment of Pediatric GERD

Baclofen, a γ-aminobutyric acid receptor agonist, has been shown to reduce the episodes of gastroesophageal reflux (GER) by reducing the incidence of transient lower esophageal sphincter relaxations. Although baclofen has been shown to reduce reflux symptoms in adults, data in pediatric patients are limited. The aim of the study was to evaluate the efficacy of baclofen in children with refractory GER. Medical charts of patients 1 to 18 years of age treated with baclofen for persistent GER symptoms were reviewed retrospectively. Short-term (at first clinic visit) and long-term (12 months) clinical responses were assessed. A total of 53 patients were included in the final analysis. The mean duration of illness was 1.5 years and the mean age was 6.1 years. All of the patients were taking either once- (53%) or twice-daily (47%) doses of proton pump inhibitors (PPIs) at the time of initiation of baclofen. Thirty-five (66%) patients experienced a significant reduction in clinical symptoms at their first follow-up visit. In the remaining 18 patients, however, baclofen was stopped because of either no response (n = 15) or adverse events (n = 3). A total of 27 patients continued treatment and were assessed for long-term response. Of those, 22 (81%) had a sustained response to baclofen at 12 months, whereas 5 (19%) lost response. We recognized no clinical characteristic differences between those with and without a response to baclofen at either time point. Baclofen can be used as supplemental therapy to proton pump inhibitors in children with refractory GER; however, prospective trials are needed to further validate our results and assess safety.

Effect of transoral incisionless fundoplication on reflux mechanisms

Transoral incisionless fundoplication (TIF) is a new endoscopic treatment option for gastroesophageal reflux disease (GERD). The mechanisms underlying the anti-reflux effect of this new procedure have not been studied. We therefore conducted this explorative study to evaluate the effect of TIF on reflux mechanisms, focusing on transient lower esophageal sphincter relaxations (TLESRs) and esophagogastric junction (EGJ) distensibility. GERD patients (N = 15; 11 males, mean age 41 years, range 23-66), dissatisfied with medical treatment were studied before and 6 months after TIF. We performed 90-min postprandial combined high-resolution manometry and impedance-pH monitoring and an ambulatory 24-h pH-impedance monitoring. EGJ distensibility was evaluated using an endoscopic functional luminal imaging probe before and directly after the procedure. TIF reduced the number of postprandial TLESRs (16.8 ± 1.5 vs. 9.2 ± 1.3; p < 0.01) and the number of postprandial TLESRs associated with reflux (11.1 ± 1.6 vs. 5.6 ± 0.6; p < 0.01), but the proportion of TLESRs associated with reflux was unaltered (67.6 ± 6.9 vs. 69.9 ± 6.3 %). TIF also led to a decrease in the number and proximal extent of reflux episodes and an improvement of acid exposure in the upright position; conversely, TIF had no effect on the number of gas reflux episodes. EGJ distensibility was reduced after the procedure (2.4 ± 0.3 vs. 1.6 ± 0.2 mm(2)/mmHg; p < 0.05). TIF reduced the number of postprandial TLESRs, the number of TLESRs associated with reflux and EGJ distensibility. This resulted in a reduction of the number and proximal extent of reflux episodes and improvement of acid exposure in the upright position. The anti-reflux effect of TIF showed to be selective for liquid-containing reflux only, thereby preserving the ability of venting gastric air.

Inspiratory muscle training improves antireflux barrier in GERD patients

The crural diaphragm (CD) is an essential component of the esophagogastric junction (EGJ), and inspiratory exercises may modify its function. This study's goal is to verify if inspiratory muscle training (IMT) improves EGJ motility and gastroesophageal reflux (GER). Twelve GER disease [GERD; 7 males, 20-47 yr, 9 esophagitis, and 3 nonerosive reflex disease (NERD)] and 7 healthy volunteers (3 males, 20-41 yr) performed esophageal pH monitoring, manometry, and heart rate variability (HRV) studies. A 6-cm sleeve catheter measured average EGJ pressure during resting, peak inspiratory EGJ pressures during sinus arrhythmia maneuver (SAM) and inhalations under 17-, 35-, and 70-cmH2O loads (TH maneuvers), and along 1 h after a meal. GERD patients entered a 5-days-a-week IMT program. One author scored heartburn and regurgitation before and after IMT. IMT increased average EGJ pressure (19.7 ± 2.4 vs. 29.5 ± 2.1 mmHg; P < 0.001) and inspiratory EGJ pressure during SAM (89.6 ± 7.6 vs. 125.6 ± 13.3 mmHg; P = 0.001) and during TH maneuvers. The EGJ-pressure gain across 35- and 70-cmH2O loads was lower for GERD volunteers. The number and cumulative duration of the transient lower esophageal sphincter relaxations decreased after IMT. Proximal progression of GER decreased after IMT but not the distal acid exposure. Low-frequency power increased after IMT and the higher its increment the lower the increment of supine acid exposure. IMT decreased heartburn and regurgitation scores. In conclusion, IMT improved EGJ pressure, reduced GER proximal progression, and reduced GERD symptoms. Some GERD patients have a CD failure, and IMT may prove beneficial as a GERD add-on treatment.

Functional testing: pharyngeal pH monitoring and high‐resolution manometry

The following paper on functional testing of the pharynx includes commentaries on the use of 24-h pH-impedance testing to identify patients with nonacid reflux and the caveats associated with automatic and visual analysis; the potential diagnostic yield of ambulatory high-resolution manomentry (HRM), particularly in identifying non-cardiac chest pain and transient lower esophageal sphincter relaxations; the differential manometric identification of conditions facilitated by using solid swallows, and the advantages of the newly developed ResTech oropharyngeal pH probe in the detection of proximal reflux events.

Studying of Gastroesophageal Reflux Disease with High-Resolution Esophageal Manometry in Different Positions

Purpose: High-resolution esophageal manometry (HREM) is usually performed in supine position. While it is known that posture has effect on gastroesophageal reflux (GER), studies describing the effect of posture on HRM measurements in gastroesophageal reflux disease GERD are lacking. The aim of this study is to compare the impact of different body positions on HREM recording in patients with GERD. Methods: Prospective study included 42 patients presented with typical and atypical GER symptoms had undergone HREM. A solid-state HREM assembly with 32 circumferential sensors spaced 1 cm apart (Unisensor) was used in the study, plotting graphs with high resolution color topography and pressure waves (GI Solar MMS). HREM recording was done while the patients is fasting and in different positions: recumbent at LT side, RT side, supine and sitting position; 10 minutes each. Patients were given ten 5-ml water swallows in each position. Pressure profiles across the esophagogastric junction (EGJ), upper esophageal sphincter (UES), peristaltic integrity, transient lower esophageal sphincter relaxations (TLESRs) were analyzed and interpreted according to Pandolfino et al, Am J Gastroenterol 2008;103:27. Results: A total of 1680 water swallows in different positions were analyzed. RT recumbent position had the lowest EGJ pressure, and the highest number of TLESRs. On the other hand, change of body position did not significantly change EGJ length, UES pressure, % of peristaltic contractions, and upper and lower body contraction amplitude (table 1). Normal body peristalsis was found in 47.7% of patients, while weak peristalsis with small peristaltic defects, large peristaltic defects, aperistlasis and distal esophageal spasm were found in 26.3%, 14.3%, 2.3%, and 9.4%, respectively. Hiatal hernia was observed manometrically in 14.3% of patients.Table 1: HREM measurements in different body positionsConclusion: RT recumbent position showed the lowest EGJ pressure and the highest number of TLESRs. Sitting, LT recumbent and supine positions did not significantly affect HREM measurements. Ineffective esophageal motility disorder is a common finding with GERD.

Waist belt and central obesity cause partial hiatus hernia and short-segment acid reflux in asymptomatic volunteers

ObjectiveThere is a high incidence of inflammation and metaplasia at the gastro-oesophageal junction (GOJ) in asymptomatic volunteers. Additionally, the majority of patients with GOJ adenocarcinomas have no history of reflux...

Novel partial 5HT3 agonist pumosetrag reduces acid reflux events in uninvestigated GERD patients after a standard refluxogenic meal: a randomized, double-blind, placebo-controlled pharmacodynamic study

Low basal lower esophageal sphincter (LES) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease (GERD). Pumosetrag, a novel selective partial 5HT3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure (LESP), and specific symptoms in patients with GERD receiving a refluxogenic meal. Patients with GERD, who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8mg) or placebo. Before and after 7days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal. A total of 223 patients with GERD [125 (56%) women, mean (SD) age=36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p>0.5); however, significant treatment effects (p<0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2mg (10.8±1.1), 0.5mg (9.5±1.1), and 0.8mg (9.9±1.1) compared with placebo (13.3±1.1). Significant treatment effects (p<0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5mg (10%) and 0.8mg (10%) compared with placebo (16%). In GERD, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1-week treatment period.

Systematic review: relationships between sleep and gastro-oesophageal reflux

Gastro-oesophageal reflux disease (GERD) adversely impacts on sleep, but the mechanism remains unclear. To review the literature concerning gastro-oesophageal reflux during the sleep period, with particular reference to the sleep/awake state at reflux onset. Studies identified by systematic literature searches were assessed. Overall patterns of reflux during the sleep period show consistently that oesophageal acid clearance is slower, and reflux frequency and oesophageal acid exposure are higher in patients with GERD than in healthy individuals. Of the 17 mechanistic studies identified by the searches, 15 reported that a minority of reflux episodes occurred during stable sleep, but the prevailing sleep state at the onset of reflux in these studies remains unclear owing to insufficient temporal resolution of recording or analysis methods. Two studies, in healthy individuals and patients with GERD, analysed sleep and pH with adequate resolution for temporal alignment of sleep state and the onset of reflux: all 232 sleep period reflux episodes evaluated occurred during arousals from sleep lasting less than 15 s or during longer duration awakenings. Six mechanistic studies found that transient lower oesophageal sphincter relaxations were the most common mechanism of sleep period reflux. Contrary to the prevailing view, subjective impairment of sleep in GERD is unlikely to be due to the occurrence of reflux during stable sleep, but could result from slow clearance of acid reflux that occurs during arousals or awakenings from sleep. Definitive studies are needed on the sleep/awake state at reflux onset across the full GERD spectrum.

Pathophysiology of gastro‐esophageal reflux disease: a role for mucosa integrity?

Gastro-esophageal reflux disease (GERD) is very prevalent and has a high burden on health security system costs. Nevertheless, pathophysiology is complex and not well-understood. Several mechanisms have been proposed: decreased salivation, impaired esophageal clearance, decreased lower esophageal sphincter pressure resting tone, presence of hiatal hernia, increased number of transient lower esophageal sphincter relaxations (TLESRs), increased acid, and pepsin secretion, pyloric incompetence provoking duodeno-gastro-esophageal reflux of bile acids and trypsin. Independent of the relevance of each mechanism, the ultimate phenomenon is that mucosal epithelium is exposed for a longer time to agents as acid and pepsin or is in contact to luminal agents not commonly present in gastric refluxate as trypsin or bile acids. This leads to a visible damage of the epithelium (erosive esophagitis -EE) or impairing mucosal integrity without any sign of macroscopic alteration as occurs in non-erosive reflux disease (NERD). Luminal factors are not the only responsible for such impairment; more recent data indicate that endogenous factors may also play a role. This review will update the most recent findings on the putative pathophysiological mechanisms and specially will focus on the role of esophageal mucosal integrity in GERD. Methodologies used for the evaluation of mucosal integrity, its relevance in EE and NERD, its involvement in symptoms perception and the effect of luminal and endogenous factors will be discussed.

A phenomenological model for the photocurrent transient relaxation observed in ZnO-based photodetector devices.

We present a phenomenological model for the photocurrent transient relaxation observed in ZnO-based metal-semiconductor-metal (MSM) planar photodetector devices based on time-resolved surface band bending. Surface band bending decreases during illumination, due to migration of photogenerated holes to the surface. Immediately after turning off illumination, conduction-band electrons must overcome a relatively low energy barrier to recombine with photogenerated holes at the surface; however, with increasing time, the adsorption of oxygen at the surface or electron trapping in the depletion region increases band bending, resulting in an increased bulk/surface energy barrier that slows the transport of photogenerated electrons. We present a complex rate equation based on thermionic transition of charge carriers to and from the surface and numerically fit this model to transient photocurrent measurements of several MSM planar ZnO photodetectors at variable temperature. Fitting parameters are found to be consistent with measured values in the literature. An understanding of the mechanism for persistent photoconductivity could lead to mitigation in future device applications.

Physiological mechanical stimulation activates isolated myenteric neurons

The enteric nervous system contains neurons that are able to regulate and control gastrointestinal functions at a local level independently from the central nervous system. The myenteric plexus is sandwiched between the longitudinal and circular muscle layer and therefore strategically well-suited to encode transient or sustained muscle contraction or relaxation that occur during tonic or phasic motor activity. We aimed to study the mechanosensitive properties of myenteric neurons by applying stimuli that mimic their physiological deformation during musle activity.

Abstract 202: Aging Alters the Electrical and Mechanical properties of LV Myocytes

Aging results in delays in the electrical recovery of the heart, enhancing the risk of malignant ventricular arrhythmias and sudden death. But whether altered electrical properties affect myocardial mechanical performance remains unclear. The aim of this study was to establish the ionic basis for the protracted repolarization of the senescent heart, and to determine whether these electrical changes impact on myocardial contractility. For this purpose, electrophysiological analyses were conducted in vivo and in isolated LV myocyte preparations from mice ranging from 3 to 30 months of age. Electrocardiographic parameters were preserved from 3 to 12 months of age, whereas animals 2 years or older presented prolonged PR, QRS and QT intervals. These in vivo results were confirmed in the isolated organ, using Langendorff perfused hearts. Myocytes from 30 months old mice showed longer early and late repolarization phases of the action potential (AP), in comparison with cells from animals at 3 months. By voltage-clamp, the density of the transient outward K+ current (Ito) was significantly reduced in old, whereas the late Na+ current (INaL) was increased, changes consistent with the prolonged AP of old cells. Additionally, by Western blotting, the SCN1B subunit, involved in Na+ channel gating, was reduced with age. Using field stimulation, old myocytes presented slower Ca2+ transient decay and relaxation, in comparison to young. Blockade of INaL with mexiletine in old myocytes shortened the AP duration, and fastened the decay of Ca2+ transients and relaxation. To assess the functional impact of INaL on the myocardium, papillary muscles were studied in an isometric system. Using tension-length protocols, old muscles presented elevated diastolic tension with respect to young. Importantly, inhibition of INaL in old muscles reduced diastolic tension, and attenuated the active developed force. Conversely, increasing INaL in the myocardium of young mice with anemonetoxin had opposite effects. Overall, these data indicate that aging results in a prolongation of the AP mediated, at least in part, by enhanced INaL. The prolonged repolarization of the AP contributes to the slower clearance of diastolic Ca2+ from the cytoplasm, resulting in protracted relaxation phase.

Postprandial cardiac vagal tone and transient lower esophageal sphincter relaxation (TLESR)

Transient lower esophageal sphincter relaxation (TLESR) is a vagally mediated reflex that occurs most frequently after a meal. Cardiac vagal tone (CVT) decreases after a meal, and correlates with changes in gastric electrical activity. Furthermore, decreased CVT has been reported in patients with gastro-esophageal reflux disease. We therefore aimed to characterize the association between postprandial changes in CVT and the occurrence of TLESR and reflux. Ten healthy volunteers underwent simultaneous autonomic nervous system, gastric myoelectric activity, lower esophageal-sphincter pressure, and reflux monitoring for 30min in the fasting state, followed by a standard meal, and a further 4h postprandially. Results are in mean±SEM. The number of TLESRs (P<0.0001) and reflux episodes (P<0.0001) increased after the meal, while CVT decreased (P<0.01). Cardiac sensitivity to baroreceptor reflex (CSB) showed similar time course changes to CVT (P=0.06). During the first postprandial hour there was a strong correlation between the number of TLESRs and reflux episodes with CVT (R(2) =0.51 and R(2) =0.50, respectively; P<0.05). There was also an increase in the dominant power and power ratio on electrogastrography (P<0.05) after the meal. In healthy volunteers, the increase in the number of TLESRs and reflux episodes after a meal occurred mostly at a time of reduced CVT. Further studies should explore whether modulation of CVT can modify frequency of TLESRs and also this relationship should be further explored in patients with reflux disease.

Impedance-High Resolution Manometry Analysis of Patients With Nonerosive Reflux Disease

Transient lower esophageal sphincter relaxations (TLESRs) contribute to episodes of reflux. Few studies have assessed the frequencies or compositions of TLESRs and reflux episodes in patients with reflux disease. We used combined high-resolution manometry and impedance monitoring to analyze reflux episodes and esophageal motility in these patients, compared with those of healthy individuals. We evaluated the frequency of TLESRs and the relationship between the reflux pattern and esophageal pressures during TLESRs in 14 patients with nonerosive reflux disease (NERD) and 11 controls. Study participants underwent combined high-resolution manometry and impedance monitoring before and 60 minutes after a solid and liquid meal. The diagnosis of NERD was confirmed by a 24-hour pH impedance test. The frequency of TLESRs did not differ between patients with NERD and controls. In patients with NERD, TLESRs were associated more often with reflux episodes than in controls (93% ± 6% vs 66% ± 19%; P < .05). Patients with NERD had a higher percentage of pure liquid reflux episodes (33% ± 15% vs 10% ± 2%; P < .05), whereas controls had a higher percentage of mixed reflux episodes (45% ± 16% vs 67% ± 17% in patients with NERD; P < .05). Patients with NERD also had a higher percentage of reflux (liquid and mixed) associated with common cavities (74% ± 18% vs 50% ± 20% in controls; P < .05). In contrast to previous studies, we found that TLESRs are associated more often with reflux in patients with NERD than control subjects; this association increases when only liquid and mixed refluxes are considered. These findings indicate that factors involved in the occurrence of reflux in patients with NERD during TLESRs are different from those in healthy subjects.

Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels

German chamomile (Matricaria recutita L.), a widely-used herbal medicine, has been reported to have a wide range of biological effects, including smooth muscle relaxation. The aim of this study was to compare the effects of representative compounds from chamomile (apigenin, luteolin, (−)-α-bisabolol, farnesene, umbelliferone; 3–30μM) on vascular tone using porcine coronary and splenic arteries mounted for isometric tension recording in isolated tissue baths and precontracted with the thromboxane-mimetic U46619.Apigenin, luteolin, and (−)-α-bisabolol produced slow, concentration-dependent relaxations in both the coronary and splenic arteries that were not blocked by inhibition of nitric oxide synthase or potassium channels. Removal of extracellular calcium inhibited the relaxations to all three compounds, and these compounds also inhibited calcium re-addition-evoked contractions, indicating that the relaxation response may be mediated through inhibition of calcium influx. Apigenin and luteolin, but not (−)-α-bisabolol, enhanced the relaxation to the nitric oxide donor sodium nitroprusside, indicating that apigenin and luteolin may act to regulate cyclic GMP levels. Umbelliferone produced a rapid, transient relaxation in the splenic artery, but not the coronary artery, that was inhibited by l-NAME and removal of the endothelium, suggesting an influence on nitric oxide production. Farnesene, at concentrations up to 30μM, was without effect in either blood vessel. In conclusion, hydroxylated compounds (apigenin, luteolin and (−)-α-bisabolol) found in chamomile all caused a slow relaxation of isolated blood vessels through an effect on calcium influx. Umbelliferone, on the other hand, produced a rapid, transient relaxation dependent upon release of nitric oxide from the endothelium.

Specific Movement of Esophagus During Transient Lower Esophageal Sphincter Relaxation in Gastroesophageal Reflux Disease

Background/AimsTransient lower esophageal sphincter relaxation (TLESR) is the main mechanism of gastroesophageal reflux disease (GERD). The aim of this study was to investigate the characteristics of transient lower esophageal sphincter movement in patients with or without gastroesophageal reflux by high-resolution manometry (HRM).MethodsFrom June 2010 to July 2010, we enrolled 9 patients with GERD (GERD group) and 9 subjects without GERD (control group), prospectively. The manometry test was performed in a semi-recumbent position for 120 minutes following ingestion of a standardized, mixed liquid and solid meal. HRM was used to identify the frequency and duration of TLESR, esophageal shortening length from incomplete TLESR, upper esophageal sphincter (UES) response, and the related esophageal motor responses during TLESR.ResultsTLESR occurred in 33 in the GERD group and 34 in the control group after 120 minutes following food ingestion. Duration of TLESR and length of esophageal shortening did not differ between 2 groups. UES pressure increase during TLESR was mostly detected in patients with GERD, and UES relaxation was observed frequently in the control group during TLESR. TLESR-related motor responses terminating in TLESR were predominantly observed in the control group.ConclusionsIncreased UES pressure was noted frequently in the GERD group, suggesting a mechanism for preventing harmful reflux, which may be composed mainly of fluid on the larynx or pharynx. However, patients with GERD lacked the related motor responses terminating in TLESR to promote esophageal emptying of refluxate.

Force enhancement in lengthening contractions of cat soleus muscle in situ: transient and steady-state aspects

Force enhancement (FE) associated with lengthening is a well-accepted phenomenon of active skeletal muscle, but the underlying mechanism(s) remain unknown. Similar to force depression (FD) following active shortening, the mechanism of FE may be attributed, at least in part, to cross-bridge kinetics. To examine this relationship, a post hoc analysis was performed on the transient force relaxation phase of previous in-situ FE experiments in soleus muscle-tendon units of anesthetized cats. For each muscle (n = 8), nine eccentric lengthenings (3 amplitudes, 3 velocities) were performed while tetanically stimulated (3T at 30 Hz, 3× α motorneuron, 35 ± 1°C). To determine transient aspects of FE, the period immediately following stretching was fit with an exponential decay function (R2 > 0.95). Statistical analyses revealed that total steady-state FE (FESS) increased with stretching amplitude and applied mechanical work. A positive relationship was observed between the active FESS and rate of force decay (k), indicating that a kinetic mechanism may explain active FE. However, for all muscles and stretch conditions, there was no correlation between the total amount of FESS and rate of decay. Therefore, FE cannot be explained solely by an active FE mechanism involving the interaction of actin and myosin. Rather, these findings suggest a combination of underlying mechanisms, including a kinetic mechanism for active FE, contributions of a passive elastic element, and possibly an activatable passive component operating outside of actin–myosin cross-bridging. Moreover, this transient analysis identifies that FE is not simply the opposite of FD, and its underlying mechanism(s) cannot simply be the opposite in nature.