Hypertrophy of the muscularis propria of the lower esophageal sphincter and the body of the esophagus in patients with primary motility disorders of the esophagus

OBJECTIVES: Patients with diffuse esophageal spasm (DES) and nutcracker esophagus/high amplitude esophageal contraction (HAEC) have a thicker esophageal muscularis propria than do healthy subjects. The goals of this study were to determine the esophageal muscle cross-sectional area (MCSA), a measure of muscle mass, in patients with achalasia of the esophagus; and to compare it with that in patients with DES, patients with HAEC, and normal subjects. METHODS: Using a high-frequency ultrasound probe catheter, concurrent manometry and ultrasound images of the esophagus were recorded in four subject groups: normal volunteers, patients with HAEC, patients with DES, and patients with achalasia of the esophagus. Recordings were obtained from the lower esophageal sphincter (LES) and multiple sites in the esophagus 2, 4, 6, 8, and 10 cm above the LES. RESULTS: The LES and esophageal muscle thickness as well as esophageal MCSA were greater in all three patient groups than in the normal subject group. Muscle thickness and MCSA were observed to be greatest in patients with achalasia, which were greater than in patients with DES, which were greater than in those with HAEC, which in turn were greater than in normal subjects. CONCLUSIONS: We propose that an increase in the MCSA is an important feature of patients with primary motility disorders of the esophagus. The degree of increase in muscle mass may be an important determinant of the type and the severity of esophageal motor dysfunction.     

Manometry and impedance characteristics of achalasia. Facts and myths

BACKGROUND: Achalasia is defined manometrically by an aperistaltic esophagus. Variations in the manometric findings occur in achalasia suggesting that all manometric features should not be required to diagnose achalasia. Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) allows both a functional and a manometric evaluation of esophageal motility and identifies chronic fluid retention. AIM: To compare manometric and MII characteristics in patients with achalasia. METHODS: Retrospective review of 73 MII-EM tracings from patients with achalasia done in our laboratory between October 2001 and December 2004 (38 females; mean age=53.5 y). Patients with previous esophageal interventions were excluded. Manometric and MII characteristics were identified and compared during 10 liquid and 10 viscous swallows. Patients were also divided into 2 groups: vigorous achalasia (VA) and achalasia. RESULTS: Twenty-two of the seventy-one (31%) achalasia patients had a hypertensive lower esophageal sphincter (LES). The mean lower esophageal sphincter pressure (LESP) for the 71 patients with achalasia was 37.9+/-21.2 mm Hg compared with 27.3+/-9.3 mm Hg (P<0.05) in the 73 patients with normal motility. The mean LESP in patients with achalasia was 36+/-20.3 mm Hg compared with 47+/-23.2 mm Hg (P<0.05) in patients with VA. Elevated intraesophageal pressure (IEP) was noted in 45/73 (61.6%). The mean LESP in this group was 41.1+/-22.9 mm Hg compared with 32.5+/-17 mm Hg (P<0.05) with normal IEP. The mean baseline impedance for achalasia was 801+/-732 compared with 1265.2+/-829.5 Omega (P<0.05) for the VA patients. CONCLUSIONS: Most patients with achalasia have elevated IEP, elevated LES residual pressure, normal LES pressure, and low baseline impedance. All manometric features should not be required to diagnose achalasia. Patients with an elevated IEP are likely to have an elevated LES pressure and LES residual pressure. Low MII values identify chronic fluid retention and helps confirm the diagnosis.     

Esophageal manometry: a comparison of findings in younger and older patients

Objective: We sought to determine the utility of esophageal manometry in an older patient population.
Methods: Consecutively performed manometry studies (470) were reviewed and two groups were chosen for the study, those ≥ 75 yr of age (66 patients) and those ≤ 50 years (122 patients). Symptoms, manometric findings (lower esophageal sphincter [LES], esophageal body, upper esophageal sphincter [UES]) and diagnoses were compared between the groups.
Results: Dysphagia was more common (60.6% vs 25.4%), and chest pain was less common (17.9 vs 26.2%) in older patients. In the entire group, there were no differences in LES parameters. Older patients with achalasia had lower LES residual pressures after deglutition (2.7 vs 12.0 mm Hg), but had similar resting pressures (31.4 vs 35.2 mm Hg) compared with younger achalasia patients. Duration and amplitude of peristalsis were similar in both groups, whereas peristaltic sequences were more likely to be simultaneous in the older group (15% vs 4%). The UES had a lower resting pressure in the older patients (49.6 vs 77.6 mm Hg) and a higher residual pressure (2.0 vs −2.7 mm Hg). The older patients were less likely to have normal motility (30.3% vs 44.3%) and were more likely to have achalasia (15.2% vs 4.1%) or diffuse esophageal spasm (16.6% vs 5.0%). When only patients with dysphagia were analyzed, achalasia was still more likely in the older group (20.0% vs 12.9%).
Conclusions: When older patients present with dysphagia, esophageal manometry frequently yields a diagnosis to help explain their symptoms.     

High vasoactive intestinal polypeptide plasma levels in patients with Barrett's esophagus

We have evaluated the correlation between vasoactive intestinal polypeptide (VIP) plasma concentration and severity of gastroesophageal reflux in patients with Barrett's esophagus and the possible differences in the VIP values of these patients compared with healthy volunteers. We also evaluated the relation between VIP plasma concentration and lower esophageal sphincter (LES) pressure in 24 patients with Barrett's esophagus. The mean VIP plasma concentration in 14 patients with severe gastroesophageal reflux was 25.6 +/- 0.75 pg/ml, significantly higher than the mean value observed in 10 patients with moderate reflux (18.9 +/- 0.67 pg/ml) (p less than 0.01). The mean LES resting pressure was significantly lower in the group of patients with severe gastroesophageal reflux than that observed in patients with moderate reflux (3 +/- 0.64 and 10.3 +/- 0.69 mm Hg, respectively; p less than 0.01). The mean VIP plasma concentration in 11 healthy volunteers (20.6 +/- 0.65 pg/ml) was significantly lower than the mean value observed in the subgroup of patients with severe gastroesophageal reflux (p less than 0.01). VIP values in patients with moderate reflux were not significantly different from those observed in our volunteers. There was a significant correlation between LES pressure and VIP plasma level (r = -0.9253; p less than 0.01). In conclusion, it is possible that the decreased LES resting pressure observed in patients with Barrett's esophagus and severe gastroesophageal reflux may be due to impairment of the VIPergic innervation, resulting in an increased local VIP release with possible overflow to peripheral plasma.     

The effect of erythromycin on human esophageal motility is mediated by serotonin receptors

OBJECTIVE: Erythromycin exhibits prokinetic properties. The drug enhances esophageal and gastric motility by acting as a motilin agonist and promoting acetylocholine release. 5-HT3 receptors are involved in the spontaneously occurring migrating motor complex and the effect of erythromycin on antral motility in dogs. The aim of the study was to investigate the hypothesis that 5-HT3 receptors are also involved in the action of erythromycin on the human esophagus. METHODS: A total of 18 healthy volunteers underwent standard esophageal manometry on three different occasions in a double-blind, placebo-controlled, randomized manner, as follows: 1) after placebo, 2) after 200 mg of erythromycin i.v., and 3) after 200 mg of i.v. erythromycin subsequent to pretreatment with either 4 mg of i. v. ondansetron (serotonin receptor antagonist) (10 subjects) or 12 microg/kg of i.v. atropine (8 subjects). RESULTS: Erythromycin significantly increased a) the amplitude of peristalsis at 5 cm (from 87 +/- 19 mm Hg to 108 +/- 26 mm Hg; p = 0.0007), 10 cm (from 72 +/- 24 mm Hg to 81 +/- 26 mm Hg; p = 0.016), and 15 cm (from 47 +/- 15 mm Hg to 55 +/- 17 mm Hg; p = 0.014) proximal to LES, b) the duration of peristalsis at 5 cm (from 4.5 +/- 0.9 s to 5.7 +/- 1.2 s; p < 0.0001) and 10 cm (from 4.1 +/- 1 s to 4.9 +/- 1 s; p < 0.0001) proximal to the LES and c) the strength of peristalsis at 5 cm proximal to the LES (from 180 +/- 49 mm Hg x s to 276 +/- 100 mm Hg x s; p < 0.0001), and decreased the velocity of peristalsis at distal esophagus (from 4.1 +/- 1 cm/s to 3.8 +/- 0.9 cm/s; p = 0.03). In addition, erythromycin significantly increased the resting pressure of the LES (from 36 +/- 10 mm Hg to 44 +/- 12 mm Hg; p = 0.002). Pretreatment with ondansetron totally reversed all of the effects of erythromycin to the placebo state. Pretreatment with atropine not only prevented the effects of erythromycin, but it reduced the amplitude and strength of peristalsis at the distal esophagus at significantly lower levels than after placebo. CONCLUSIONS: Erythromycin exerts its prokinetic action on the lower esophagus by stimulating cholinergic pathways. This action includes not only an increase in LES pressure, but significant increases in the amplitude and duration of esophageal peristalsis, as well. 5-HT3 receptors are also involved in this process.     

Transcutaneous electrical nerve stimulation decreases lower esophageal sphincter pressure in patients with achalasia

Vasoactive intestinal peptide (VIP) is believed to be an inhibitory neurotransmitter responsible for lower esophageal sphincter (LES) relaxation. In patients with achalasia the concentration of VIP and the number of VIP-containing nerve fibers are reduced or absent. It has been suggested that the response to low-frequency transcutaneous electrical nerve stimulation (TENS) may be mediated by a nonadrenergic noncholinergic pathway in which the release of VIP is responsible for the smooth muscle relaxation. The present study was designed to evaluate the effect of TENS on LES pressure and on VIP plasma concentrations in six patients with achalasia (five female, one male). TENS was performed daily during one week for 45-min sessions with a pocket stimulator that delivered low-frequency pulses (6.5 Hz), at 10 pulses/sec of 0.1-msec duration at intensities of 10-20 mA until rhythmic flexion of the fingers was obtained without producing pain. LES pressure and VIP levels were obtained before TENS, after the first 45-min session, and after a week of daily stimulation. After 45-min, TENS produced a significant reduction (P less than 0.01) in LES resting pressure from the mean value 56 +/- 6.4 mm Hg to 42.3 +/- 6.4 mm Hg; with LES relaxation improvement from 50.6 +/- 3% to 63.1 +/- 3.2% (P less than 0.01). After one week of daily TENS, an additional reduction in LES resting pressure (40.3 +/- 4 mm Hg) was observed (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of vasoactive intestinal polypeptide on the lower esophageal sphincter in achalasia.

Vasoactive intestinal polypeptide (VIP) is one of the main neurotransmitters implicated in the relaxation of the lower esophageal sphincter (LES). The effect of exogenous VIP on LES motor activity was determined by esophageal manometry. LES pressure (LESP) and LES relaxation were compared in four healthy volunteers and in six patients with achalasia. The effects of intravenous doses of 1.5, 3, and 5 pmol.kg-1.min-1 of VIP were compared with placebo. Neither placebo nor 3 and 5 pmol.kg-1.min-1 of VIP produced any effect on esophageal motility in healthy volunteers. In achalasia the three doses of VIP caused a dose-dependent decrease in LESP with a significant improvement in LES relaxation. A dose of 5 pmol.kg-1.min-1 produced a maximal decrease of 51% in LESP. A beta-adrenergic agonist, isoproterenol, caused a decrease in LESP both in healthy volunteers and in patients with achalasia without improving LES relaxation. In summary, intravenous VIP improved LES relaxation and caused a decrease in LESP in patients with achalasia without affecting LESP in healthy volunteers, indicating that the LES muscle in achalasia is supersensitive to VIP. The current study suggests that a selective damage in the noncholinergic nonadrenergic innervation of the esophagus is in part responsible for the motor alteration seen in these patients. The findings and the inability of isoproterenol to improve LES relaxation despite decreasing LESP support a role in VIP as a indicator of LES relaxation.     

Cisapride effects on canine lower esophageal sphincter under various pharmacological pretreatments.

Cisapride (Ci) stimulates lower esophageal sphincter pressure (LESP). This study aims to test whether the effect of Ci on LES in vivo is still present if LES is relaxed by atropine (Atr) and nifedipine (Nife) prior to the administration of Ci. LESP was continuously recorded by manometry in 6 mongrel dogs with esophageal fistulae. Ci was given as an intravenous bolus following either Atr (40 micrograms/kg i.v.) or Nife (20 mg subl.) at the time of maximal LESP decrease (5/15 min later). Basal LES values ranged between 24.5 +/- 2.5 mm Hg (Atr group) and 23.8 +/- 3.9 mm Hg (Nife group). Following Atr, LESP decreased to a minimal value of 7.0 +/- 0.5 mm Hg; after Nife LESP decreased to a minimal value of 12.3 +/- 2.0 mm Hg. Additional administration of Ci was not able to reincrease LESP. We conclude that the action of Ci on LES cannot take place if (1) muscarinergic receptors are blocked by Atr and (2) the Ca2+ activation system is blocked by Nife. Our results suggest that the action of cisapride on LES, as its action on gastrointestinal smooth muscle cells, is mediated by postsynaptic enhancement of acetylcholine release.     

Drug effects on esophageal smooth muscle

To assess which manometric parameters should be evaluated to discriminate health and esophageal motility disorders, we established normal values for lower esophageal sphincter pressure (LESP), LES residual pressure, percentage and duration of LES relaxation, contraction amplitude in the esophageal body, duration of the contractile waves, mode of wave propagation, and shape of contraction amplitudes as well as upper esophageal sphincter pressure (UESP) in 40 healthy volunteers. The values obtained were compared to values in 25 patients with achalasia, 48 patients with nonspecific motility disorders, and 28 patients with reflux esophagitis. Although significant differences of mean values could be found between health and diseased states of esophageal motility, it was impossible to establish clear cutoff points in individuals due to a large overlap of manometric parameters in healthy volunteers and patients. Further prospective studies are necessary to determine sensitivity, specificity, and predictive values of cutoff lines of manometric data. In addition to the inability to define esophageal motility disorders on the basis of motility parameters alone, there is a lack of correlation between the severity of esophageal symptoms and manometric findings. For example, in diffuse esophageal spasm and related disorders, amplitude, duration, configuration, and propagation of esophageal body contractions are not closely related to the severity of symptoms. In reflux esophagitis, mean LESP does not reflect the extent of symptoms or mucosal damage. Only in achalasia, do LESP and resting pressure of the esophageal body seem to be correlated to dysphagia. It is concluded that drug effects on esophageal motility should be evaluated not primarily by manometric data but by clinical effects.     

Lower esophageal sphincter relaxation characteristics using a sleeve sensor in clinical manometry

Objective: We undertook this study to determine the characteristics of swallow-induced lower esophageal sphincter (LES) relaxation in the setting of clinical manometry using a standardized methodology.
Methods: We reviewed 170 manometric recordings performed using a perfused manometric assembly with a sleeve sensor and a computer polygraph. Patients were categorized as patient controls, gastroesophageal reflux disease (GERD), diffuse esophageal spasm (DES), or achalasia. Tracing were semiautomatically analyzed for basal LES pressure, LES pressure during deglutitive relaxation (relaxation LES pressure), duration of LES relaxation, timing of LES relaxation, and the success rate of primary peristalsis.
Results: Forty-six patient controls, 93 with GERD, five with DES, and 26 with achalasia were identified. GERD and achalasia patients had lower or higher basal LES pressures than patient controls, respectively. Compared with patient controls, achalasia patients had higher relaxation LES pressures, lower percent LES relaxation, and shorter durations of LES relaxation. The best single measure for distinguishing achalasia was the relaxation LES pressure; using the 95th percentile value of patient controls (12 mm Hg) as the upper limit of normal, its sensitivity and positive predictive value for the diagnosis of achalasia were 92% and 88%, respectively. Coupled with the finding of aperistalsis, a relaxation LES pressure ≥10 mm Hg achieved 100% sensitivity and positive predictive value among these patients.
Conclusion: Sleeve sensor recording is a practical method for clinical manometry that reliably records LES relaxation characteristics and is amenable to both a standardized manometry protocol and a semiautomated analysis routine. Relaxation LES pressure has a high diagnostic value for achalasia.     

The effects of an inhaled beta(2)-adrenergic agonist on lower esophageal function: a dose-response study

STUDY OBJECTIVES: Albuterol, a beta(2)-adrenergic agonist that is commonly used to treat asthma, reduces bronchial smooth muscle tone. The pharmacodynamics of inhaled albuterol on esophageal function were studied in healthy volunteers. DESIGN: A prospective, randomized, placebo-controlled, double-blind crossover design. SETTING: An academic medical center. PATIENTS: Nine healthy volunteers (five men, four women; age, 22 to 30 years). INTERVENTIONS: Albuterol (2.5 to 10 mg) or placebo was given via nebulizer. Volunteers were studied at two sessions, 1 week apart, using a 6-cm manometry assembly and a low-compliance pneumohydraulic pump. The percentage of lower esophageal sphincter (LES) relaxation, the frequency of transient LES relaxations (TLESRs), and the amplitude, duration, and propagation velocity of esophageal contractions were measured at 5 and 10 cm above the LES. Dependent measures were evaluated using two-way, repeated-measures analysis of variance. MEASUREMENTS AND RESULTS: Albuterol therapy reduced LES basal tone in a dose-dependent manner (baseline, 17.0 +/- 2.6 mm Hg; at 10 mg, 8.9 +/- 2.1 mm Hg; p = 0.01). The frequency of TLESRs was not different from placebo (not significant). Albuterol reduced the amplitude of esophageal contractions at 5 cm above the LES (baseline, 72.5 +/- 18.6 mm Hg; at 10 mg, 48.8 +/- 10.0 mm Hg; p<0.05). A significant reduction in esophageal body contractile amplitudes was noted at 10 cm (F[1,6] = 7.05; p<0.05). CONCLUSIONS: Inhaled albuterol reduced LES basal tone and contractile amplitudes in the smooth muscle esophageal body in a dose-dependent manner. Inhaled beta(2)-agonists may increase the likelihood of acid reflux in a subset of patients who receive cumulative dosing.     

胆碱能神经对反流性食管炎食管动力的影响

目的研究内源性胆碱能神经在反流性食管炎食管动力机制异常中的作用.方法经下食管括约肌切开制备反流性食管炎的猫模型,用连续水灌注测压系统检测正常猫及反流性食管炎的猫食管体部动力;用分光光度法分别测定正常猫及反流性食管炎的猫食管中段、远段肌组织中的乙酰胆碱转移酶和乙酰胆碱酯酶活力.结果反流性食管炎组食管远段平均收缩波幅度明显低于正常对照组(P＜0.0001),食管远段传导速度低于正常对照组(P＜0.05);反流性食管炎时食管中段及远段肌组织中乙酰胆碱转移酶活力均低于正常对照组的中段及远段(P＜0.05及P＜0.0001),以远段更明显(P＜0.0001).反流性食管炎组食管中段及远段肌组织中的乙酰胆碱酯酶活力与对照组比较差异均无显著性(P＞0.05).结论反流性食管炎可导致食管远段动力低下,内源性胆碱能神经功能异常是其重要机制之一.     

Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia

The human lower esophageal sphincter (LES) is believed to be innervated by nonadrenergic, noncholinergic inhibitory nerves, and cholinergic excitatory nerves. In idiopathic achalasia, LES relaxation is abnormal because the inhibitory nerves to the sphincter are either absent or functionally impaired. The integrity of cholinergic excitatory nerves to the LES, however, has not been thoroughly evaluated. In 27 patients with untreated idiopathic achalasia, and 21 healthy volunteers, we investigated the hypothesis that postganglionic cholinergic nerves to the LES are functionally intact in achalasia. The LES responses to atropine, edrophonium, methacholine, amyl nitrite, and pentagastrin were assessed. In 2 achalasia patients, patterns of fasting motor activity in the LES were investigated during overnight manometric studies. Resting LES pressure was significantly greater in the achalasia patients, 41 +/- 4 mmHg (mean +/- SE), than in the normal subjects, 20 +/- 2 mmHg. Atropine significantly reduced LES pressure in both groups by 30%-75%. Edrophonium increased LES pressure in the achalasia patients but had negligible effect on the normal subjects. The LES in achalasia patients exhibited an increased sensitivity to both methacholine and pentagastrin compared with the normal subjects. In both patients who underwent an overnight manometric study, the LES exhibited cyclic phasic contractile activity synchronous with gastric contractions during the migrating motor complex. We conclude that the study findings support the hypothesis that postganglionic cholinergic LES innervation in achalasia patients is either normal or only minimally impaired, in contrast to the marked impairment of the inhibitory nerves governing LES relaxation.     

Medical treatment of esophageal achalasia

Calcium channel blockers have been previously shown to decrease lower esophageal sphincter (LES) pressure and improve symptoms in achalasia. We performed a placebocontrolled, double-blind, crossover study to assess the effects of oral nifedipine and verapamil on LES pressure, amplitude of esophageal body contraction, and clinical symptomatology in eight patients with symptomatic achalasia diagnosed by endoscopy, barium swallow, and manometry. Patients were randomized to receive up to 20 mg nifedipine, 160 mg verapamil, or placebo and underwent esophageal manometry before (baseline) and after four weeks on each drug. Diary cards were kept to record and grade symptoms and drug plasma level determinations were correlated with manometric and clinical findings. Both nifedipine and verapamil caused a statistically significant decrease in mean LES pressure, but only nifedipine caused a significant decrease in the amplitude of contractions of the smooth muscle portion of the esophagus. No statistically significant differences in the overall clinical symptomatology were noted with any of the drugs, although some individual improvements in dysphagia and chest pain were noted. We conclude that, despite the reduction in LES pressure and contraction amplitude of the distal esophageal body, oral nifedipine and verapamil do not significantly alter the clinical symptomatology of patients with achalasia.This work was presented in part at the 50th Annual Meeting of the American College of Gastroenterology, Miami Beach, Florida, October 1985, and published in abstract form in theAmerican Journal of Gastroenterology 80:833, 1985.     

Prevalence of increased esophageal muscle thickness in patients with esophageal symptoms

BACKGROUND: Patients with achalasia, diffuse esophageal spasm (DES), and nutcracker esophagus have a thicker muscularis propria than normal subjects. The goal of our study was to determine the prevalence of increased muscle thickness in a group of unselected patients referred to the esophageal function laboratory for evaluation of the symptoms. METHODS: We studied 40 normal subjects and 94 consecutive patients. Manometry and ultrasound images were recorded concurrently, using a special custom-built catheter. Esophageal muscle thickness and muscle cross-sectional area were measured at 2 and 10 cm above the lower esophageal sphincter (LES). Patients were assigned manometric diagnosis and determination was made if they had increased muscle thickness and muscle cross-sectional area. RESULTS: Nearly all patients with well-defined spastic motor disorders, i.e., achalasia, DES, and nutcracker esophagus, revealed (a) an increase in the muscle thickness/cross-sectional area, (b) increase in esophageal muscle thickness/cross-sectional area was also seen, albeit at a lower prevalence rate, in patients with less well-characterized manometric abnormalities, i.e., hypertensive LES, impaired LES relaxation, and ineffective esophageal motility, and (c) 24% of patients with esophageal symptoms but normal manometry were also found to have an increase in muscle thickness/cross-sectional area. Dysphagia was more likely, and heartburn less likely in patients with increased muscle thickness, but there were no differences in chest pain and regurgitation symptoms between the groups. CONCLUSION: We describe, for the first time, increased muscle thickness in patients with esophageal symptoms and normal manometry. We suggest that increased esophageal muscle thickness is likely to be an important marker of esophageal motor dysfunction.     

The Effect of Verapamil on the Lower Esophageal Sphincter Pressure in Normal Subjects and in Achalasia

Verapamil hydrochloride is an organic calcium antagonist that is known to decrease the contraction of smooth muscle. The purpose of our study was to determine if verapamil has a similar effect on the resting lower esophageal sphincter pressure in normal subjects and in patients with achalasia. Esophageal manometry was performed using a continuously perfused catheter assembly. Infusion of verapamil (0.15 mg/kg) over a 2-min period resulted in a statistically significant decrease in resting lower esophageal sphincter pressure in both normal subjects (n = 8) and patients with achalasia (n = 7) within 10 min postinfusion. This study suggests that verapamil may have potential as a drug therapy in treating the clinical symptoms of achalasia and diffuse esophageal spasm.     

Alteration of esophageal peristalsis by pentagastrin in patients with diffuse esophageal spasm.

Although it has been shown that gastrin and gastric alkalinization affect the lower esophageal sphincter, in vivo studies have not demonstrated a measurable effect of pentagastrin on esophageal peristalsis. In 9 patients with diffuse esophageal spam and in 10 control subjects esophageal peristalsis was recorded before and after pentagastrin infections. Subcutaneous pentagastrin increased peak amplitude significantly more in patients, 31.2 +/- 8.1 mm Hg (mean +/- S.E.M.), than in controls, 12.1 +/- 5.1 mm Hg (P less than 0.02). Max. duration of contraction waves in patients showed a rise of 11.3 +/- 2.7 sec as compared to controls, 1.9 +/- 0.9 sec (P less than 0.01). The effect of pentagastrin on esophageal peristalsis in patients with diffuse esophageal spasm may be explained as denervation supersensitivity.     

Effect of an oral beta2-adrenergic agonist on lower esophageal sphincter pressure in normals and in patients with achalasia

The effect of the beta₂-adrenergic agonist, carbuterol, was studied on the lower esophageal sphincter (LES) pressure in normals and in patients with achalasia. In normals, the mean LES pressure decreased from 23.1±6.2 mm Hg (mean±sem) to 16.0±5.0 mm Hg at a 4.0-mg dose of carbuterol (P<0.05). In patients with achalasia, the mean LES pressure decreased from 50.1±5.1 mm Hg to 22.7±2.4 mm Hg after a 4.0-mg dose of carbuterol (P<0.01). The duration of action following oral administration exceeded 90 min. These studies indicate that the LES in man has beta₂-adrenergic receptors that mediate a reduction in pressure. The magnitude of LES pressure reduction in patients with achalasia suggests that this drug may be of therapeutic benefit.     

Endoscopic injection therapy for achalasia and other esophageal motilitydisorders

Botulinum toxin (BT) injections have been proposed to treat achalasia and hypertensive esophageal motility disorders. They affect lower esophageal sphincter (LES) and esophageal muscle function by inhibiting acetylcholine release and thus preventing neuromuscular conduction. BT injection in the LES is effective to treat achalasia but the improvement is limited to few months. As a consequence, recent guidelines recommend BT in achalasia patients who are not good candidates for more definitive therapy with pneumatic dilation or myotomy. BT might be a good option for patients with esophago-gastric junction obstruction without a firm diagnosis of achalasia. However, response to BT injection is not predictive of response to a more invasive therapy. BT injection in both the LES and the esophageal body might have a short-term efficacy to relieve dysphagia in patients with diffuse esophageal spasm or nutcracker esophagus. Usually BT is administrated as 1 cc aliquots with 20 units of toxin per milliliter into the LES and/or the esophageal body for a total dose of 100 unit international. BT injections are usually safe. Moderate chest pain might be reported following the injection. Three cases of death were reported due to acute mediastinitis and pseudoaneurysm. Finally, there is a theoretical risk of increased difficulty to perform esophageal myotomy in patients who previously received BT therapy due to the potential risk of fibrosis.     

Characterization of Esophageal Striated Muscle in Patients with Achalasia

Many studies have been conducted analyzing the manometric properties of patients with achalasia, but the striated portion of the esophagus has never been analyzed and is often overlooked. We retrospectively reviewed 120 manometric tracings (20 achalasia, 100 controls) performed between 1994 and 1997 and excluded tracings from patients with chronic cough and nutcracker esophagus. The data were assessed for age, sex, symptoms, duration of symptoms, lower esophageal sphincter pressure, gastroesophageal gradient, upper esophageal sphincter pressure, smooth muscle contraction amplitude and duration, striated muscle contraction amplitude and duration, length from upper esophageal sphincter to maximal striated muscle contraction, and esophageal length. The maximum striated muscle contraction amplitude was significantly decreased in achalasia patients with a median amplitude of 45 mm Hg (range 12–95) vs 76 mm Hg (range 30–210) in the control group (P = 0.002). Although the wave forms were similar, the maximum striated muscle contraction duration and the distance from the upper esophageal sphincter in achalasia patients was not significantly different from controls. The length of the esophagus was significantly longer in achalasia patients with a median value of 25 cm (range 21–30) vs 21 cm (range 17–26) in the control group (P < 0.001). Patients with achalasia have significantly lower maximum striated muscle contraction amplitudes and longer esophagi, but the duration of the contractions and the configuration of the wave forms are not different.