Pathogenesis of simultaneous esophageal contractions in patients with motility disorders

GASTROENTEROLOGY

1993;105:111-118

Pathogenesis of Simultaneous Esophageal Contractions in Patients With Motility Disorders JOSE

BEHAR

Department

and

PIER0

BIANCANI

of Medicine, Rhode island Hospital; and Brown University School of Medicine, Providence, Rhode Island

Background: Simultaneous and spontaneous contractions are frequently recorded in patients with esophageal motility disorders. The aim was to investigate the pathogenesis of swallow-induced simultaneous and spontaneous contractions. Methods: The pathogenesis was studied in patients with normal peristaltic contractions (control group) and in patients with functional dysphagla with either simultaneous contractions (group A), with peristaltic but prolonged contractions (group B), and with frequent spontaneous contractions (group C). Results: Simultaneous contractions had iatencies of 2.9 + 0.2 seconds compared with 6.4 + 0.2 seconds for normal peristaltic contractions and 5.8 + 0.4 seconds for prolonged peristaltic contractions. Paired swallows at intervals of 5 seconds generated one peristaltic sequence after the second swallow in subjects with normal peristalsis and two sets of contractions in patients with simultaneous contractions. Ten consecutive swallows taken at 5-second intervals inhibited the spontaneous contractions evoked by bethanechol In control subjects but had no significant effect on the spontaneous contractions of subjects with simultaneous contractions. Atropine reduced the frequency, force, and duration of the spontaneously generated contractions in group C. Conclusions: The shorter latency of simultaneous contractions may be caused by a defective deglutitive inhibitory reflex, and spontaneous contractions appear to be generated by swallow independent discharges of acetylcholine.

N

ormal esophageal motor function is characterized by a quiescent esophagus at rest, which is

stimulated by swallows that evoke peristaltic or sequential contractions able to propel food boluses from

the pharynx dysphagia

to the stomach. caused

by motility

Patients disorders

with

functional

of the esopha-

gus, such as achalasia, diffuse esophageal spasm (DES), and related motor disorders, reveal the presence of nonpropulsive or simultaneous contractions, Two types of simultaneous contractions are observed in the esophagi of patients with DES and related motor disorders depending on whether they are evoked by swallows or are spontaneous. Iv2 Most swallow-induced simultaneous contractions have only an identical onset; few of them are completely simultaneous with identi-

cal

configuration

with

endsL5;

spontaneous

pletely

simultaneous

similar

contractions with

identical

they may also have different be simultaneous

onsets,

peaks,

are frequently shape

although

configurations

only because

and com-

and may

of an identical

onset.6’7

There are also spontaneous and completely simultaneous waves characterized by a rise in pressure and are frequently dilated waves evoked

observed

esophagus result

from

in patients that creates pressure

by respiratory

complete contractions. The present motility tigate

the pathogenesis

that were swallow sence of a common

with

achalasia

a common

fluctuations

cavity;

a

these

of fluid waves

or probe

movements

studies

were designed

of simultaneous

induced

with

or spontaneous

or by into inves-

contractions in the ab-

cavity.

Materials and Methods Twenty consecutive patients with noncardiac chest pain, a normal esophageal motility and negative provocative tests were used as controls. The LES pressures were between 15 and 30 mmHg, and peristaltic contractions had normal pressures and duration, which were not different from our historical controls (n = 60 subjects); this control group had pressures between 50 and 150 mmHg (98 + 22 mmHg [mean ?z SD]) and a duration between 4 and 8 seconds (5 + 0.6 seconds). The esophagus was ruled out as the cause of the chest pain by two negative provocative tests. None of the patients experienced their chest pain during an acid infusion of the esophagus (Bernstein test) or after the subcutaneous administration of bethanechol (7 pg/kg of body weight). Patients with functional dysphagia were recruited from 86 consecutive patients studied within a 4-year period. Most patients had moderate dysphagia (at least one episode a day), and few had severe dysphagia (at least one episode of dysphagia with every meal). Thirty-six patients were excluded because (1) 5 had motility studies of very poor quality because they were unable to refrain from frequent swallows for at least 30 seconds; (2) twelve had typical motor changes of diffuse esophageal spasm; and (3) nineteen patients had Abbreviations used in this paper: DES, dlffuse esophageal spasm. 0 1993 by the American Gastroenteroiogical Assoclatlon 0016-5085/93/.$3.00

112

BEHAR AND BIANCANI

Table 1. Parameters

GASTROENTEROLOGY Vol. 105, No. 1

of Esophageal

Contractions No. of

Latency

Duration

Force

patients

(s)

(s)

(mm Hg)

20

6.4 + 0.2

5.0 f 0.2

100.5 + 5

(group A) Prolonged contractions

26

2.9 f 0.2

7.1 + 0.7=

148.1 + 19

(group 6) Spontaneous

12

5.8 I!Z0.4

11.3 f 0.9.Q

Groups Control Simultaneous

contractions

(grow Cl

12

6.2 ?I 0.7

NOTE. Values are mean k SE. ‘Values are significantly different from controls. %alues are significantly different between simultaneous

nonspecific

motility abnormalities

with intermittent

simul-

or intermittent

spon-

or occasional

taneous contractions.

None of the patients had history of

heartburn or odynophagia,

cerebrovascular

accidents, neu-

collagen disorders, or Raynaud’s phenomenon.

None of these patients had radiological

or motility abnor-

malities consistent with achalasia or scleroderma. The remaining patients with functional divided into three groups determined manometric

abnormality

109.6 f 18

and prolonged contractions.

taneous contractions

ropathies,

212.5 k 2Wr’

contractions

eluded patients in whom all the swallow-induced

contrac-

tions were simultaneous in the distal 10 cm of the esophagus (smooth

muscle segment)

with peristaltic

contractions

in

the upper third of the esophagus (striated muscle); group B (n = 12) included patients that had peristaltic contractions but were of an abnormal

duration

(9

seconds);

and in

group C (n = 12) patients had frequent spontaneous contrac-

dysphagia were

by the predominant

(Table 1): group A (n = 26) in-

tions mixed with swallow-induced

peristaltic

contractions

in the distal 7-12 cm of the esophagus. Motility studies were performed using a triple lumen tube with side openings 5 cm apart that was constantly perfused with water by a low compliance

TIME

The probe was connected

(Seconds)

pump (Arndorfer’s

pump).

to pressure transducers

that in

turn were plugged to a 6-channel

Beckman polygraph. The

chart speed was 1 or 2.5 mm/set.

Swallows were recorded

by placing a skin electrode over the region of the mylohioid muscle; the accuracy of recording

of swallows was con-

firmed by checking the timing of the swallows with respect to the pharyngeal contractions

at two different sites.

The motility of the esophagus of each patient was studied using two different protocols;

all patients had a complete

motility study, which was performed probe in l-cm

by withdrawing

the

steps from the lower esophageal sphincter

(LES) to the pharynx. At each point, patients were asked to take three dry swallows at intervals of 30 seconds or longer. Swallows

taken at shorter

intervals

were discarded.

Dry

swallows were used because of the need to accurately measure latencies; wet swallows can create an initial hump that makes impossible After completion ‘\

--

to define the onset of the contraction.* of the first protocol,

10 patients with nor-

mal peristaltic contractions and 10 patients with simultaneous contractions had a second study with the side openings of the motility probe placed at 2,7, and 12 cm above the LES; it consisted of (1) ten sets of paired wet swallows taken

Figure 1. Esophageal latency gradient of patients with normal peristalsis (0) and patients with simultaneous contractions (0). Values are mean latencies at esophageal levels that increase by 2 cm. Peristaltic contractions show a gradient with latencies that increased aborally and are progressively of longer duration; in contrast, in patients with simultaneous contractions, the latencies increased only in the upper half of the esophagus and had identical latencies in the lower half.

at 5-second intervals and (2) two sets of 10 consecutive wet swallows at 5-second intervals taken 15 minutes before and 15 minutes after the administration of subcutaneous bethanechol(7 pg/kg). Wet swallows were induced by introducing a 5-mL water bolus in the oral cavity. Furthermore, 10 patients from group C also underwent an additional study to examine the effect of 10 pg/kg of intravenous atropine on the frequency of spontaneously generated contractions in a

PATHOGENESIS

July 1993

A

PERISTALTIC

.:

OF SIMULTANEOUS

CONTRACTIONS

113

lo-minute period 15 minutes before and 15 minutes after the administration of atropine. Swallow-induced simultaneous contractions were defined by the simultaneous onset of the contractions recorded in at least two consecutive pressure sensors (5 cm); frequently, these contractions also peaked simultaneously, but they did not have the same configuration or duration. Spontaneous contractions were defined as contractions unrelated to swallows. Latency was measured from the onset of the swallow to the onset of the contraction in each step (or centimeter) of the esophagus during a complete station pull through. Force and duration of the contractions were measured at 2 cm above the LES. Each measurement was a mean of 9 dry swallows. Values are expressed as mean f SE, and statistical differences of the means were determined by applying the unpaired Student’s t test.

Results Table duration,

1 shows

the mean

and pressures

2 cm above the LES in patients contractions gia and with

abnormal

ing duration (Figure

esophageal

duration

of the latency

when

the

until

gradient

the LES

with simultaneous

A) also had a gradual

latency

Subjects of increas-

approached

patients

(group

dyspha-

contractions. had a latency

as the contraction

1); in contrast,

peristaltic

with functional

contractions

tractions

contractions

with normal

and three groups

peristaltic

+- SE of the latency,

of the esophageal

9-10 became

con-

increase

in the

cm above

the LES

flat

signifi-

and

cantly shorter than the latency of the control group. The differences in the duration of the latencies between came

peristaltic clearer

the latency

and

simultaneous

contractions

close to the LES; the mean in the control

group

be-

duration

of

was 6.4 f 0.2 seconds

(SE of mean) compared with only 2.9 +- 0.2 seconds in patients with simultaneous contractions (P < 0.001; Table

1); the latency

prolonged

and

5.8 f 0.4, which jects with peristaltic of group

5ieiz

of patients

forceful

with

contractions

peristaltic (group

was not different

from

contractions

but longer

A (P < 0.01).

The latency

control

in group

but

B) was than

subthat

C could

Figure 2. (A) Motility tracing showing the esophageal responses to paired wet swallows in patients with peristaltic contractions. As shown on the left, the esophagus of most patients with normal peristaltic contractions responded only after the second swallow; as shown on the right, the esophagus of three patients responded with one contraction after each swallow but only at 12 and 7 cm above the LES and with one contraction after the second swallow at 2 cm above the LES. (6) Motility tracing that illustrates the response of the esophagus of patients with simultaneous contractions (group A) to paired wet swallows at intervals of 5 seconds. The esophagus responded with a contraction after each swallow in all three levels of the distal 12 cm of the esophagus even though the intervals were 5 seconds.

114

BEHAR

AND

BIANCANI

not be measured

GASTROENTEROLOGY

because

of the frequent

spontaneous contractions. The mean pressures of normal tions

was 100.5 k 5 mmHg

mmHg

in group

A with

212.5 f 20 mmHg

peristaltic

compared

with

normal

peristaltic

7.1

0.7

k

The mean

contractions

was 5 f

seconds

for

simultaneous

for prolonged The

contractions

significantly

was

(P < 0.05); however,

duration

above

the LES in most

group

of 10 patients

one

after

duration

the distribution

(Figure

contractions,

mean number of esophageal contractions evoked by the first swallow of 10 paired swallows was lower in

in the lo-cm

at 30-second of

contractions, contrac-

for spontanecontrols

of the individual

subjects

intervals

with

segment was

peristaltic

after single swallows

2.8 t- 0.3 seconds.

contractions

than

above

the LES (P < 0.05; Figure

Bethanechol esophagus

produced

motility

changes

of subjects with peristaltic (Figure

Paired wet swallows taken at 5-second intervals by 10 patients with peristaltic contractions generated one peristaltic sequence that occurred after the second swallow in 7 patients (Figure 24); in the remaining 3 subjects, paired swallows elicited contractions after

unchanged. tions from

each swallow at 12 and 7 cm above the LES but only one contraction after the second swallow at 2 cm from the LES (Figure 2/l). In this group of three subjects, the mean latency was 2.9 f 0.2 seconds at 12 cm and 4.0 + 0.1 seconds at 7 cm above the LES compared with 5.4 f 0.7 seconds at 2 cm above the LES. In contrast, in patients with simultaneous contractions (group A), paired wet swallows evoked two sets of

tions

0.001)

in subjects

(56% increase)

with peristaltic

142.1

f

in patients

(P < 0.001);

contractions 0.05)

the

by swal-

whether peristaltic period, remained

in patients

and from

with

(P <

?z 10.4 mmHg

simultaneous

it also increased

from

contractions

8 to 222.1

contrac-

the duration

of the

5 f 0.2 to 6.8 4 0.4 seconds with peristaltic

(36%

contractions

(P <

6.3 + 0.4 to 8.8 + 0.5 seconds

increase) in patients with simultaneous (P < 0.01). Bethanechol also increased

(35%

contractions the frequency

of the spontaneous contractions in both groups, but they were significantly more frequent in the group with

simultaneous

contractions

Only 6 subjects with peristaltic regular tions

and sufficient

number

at 2 and 7 cm above

this study; they generated neous I

evoked

It increased the pressure of the contrac105.1 + 6.7 to 167.6 ? 10.1 mmHg (59%

and from

increase)

the

4A and B). It increased

lows, but their temporal sequence, or simultaneous in the pretreatment

increase)

in

and with simulta-

of the contractions

15

in patients

3).

neous contractions

? ?Peristaltic ??Simultaneous

The

with simultaneous contractions in all three esophageal levels and was significantly different at 2 and 7 cm

force and duration

5

2B). In this

simultaneous

values reveal that only half of the patients had longer duration (>8 seconds) whereas the other half had values that were within normal limits.

20

2

C

0.2 seconds,

than

swallow

the latency

of the simultaneous longer

patients

with

each

and at 7 and 12 cm

to

contrac-

peristaltic

tions (P < O.OOl), and 6.2 + 0.7 seconds ous contractions.

contractions

contrac-

for the group

contractions.

11.3 + 0.9 seconds

simultaneous

148 ? 19

contractions

B with prolonged

tions (P < 00.1) and 109.6 k 18 mmHg with spontaneous

of

cm above the LES in all 10 patients

simultaneous

in group

incidence

Vol. 105, No. 1

contractions

riods within

of spontaneous

developed contrac-

the LES to be included a mean

before

in

of 3.7 ? 0.4 sponta-

per 50 seconds

10 minutes

5; P < 0.01).

(Figure contractions

in two control

taking

pe-

10 consecutive

wet swallows 5 seconds apart. When 10 swallows were taken at 5-second intervals during two periods of 50

”

Distance

12

7

2 from

the

LES

(cm)

Figure 3. Number of esophageal contractions in response to the first swallows of 10 paired wet swallows taken 5 seconds apart by control subjects with peristaltic contractions (n = 6) and patients with simultaneous contractions (n = 6). The number of contractions in patients with simultaneous after the first swallow was greater than in subjects with peristaltic contractions. Normal subjects had no contractions after the first swallows 2 cm above the LES. Values are mean f SE.

seconds, the mean frequency of spontaneous contractions was reduced from 3.7 + 0.4 to 1 -t 0.4 in the esophagus with peristaltic contractions (Figure 5) or an 82% reduction from the control period (P < 0.01); it decreased from 6.7 f 0.7 to 5.9 + 0.5 in patients with simultaneous contractions or 12% reduction, which was not significantly different from the control period. Atropine was administered to patients with spontaneously generated contractions of Group C that were unrelated to swallows and were either single or repetitive in the baseline motility. This anticholinergic drug

PATHOGENESIS

July 1993

’

, SWALLOWS ;,,jjji\/;/; : ! ) : ! j I.:,/,$

produced

115

Figure 4. (A) Manometric tracings showing frequent spontaneous contractions generated by cholinergic stimulation with bethanechol in a subject with normal peristaltic contractions during a control period without swallows (upper tracing) and during a period of 10 wet swallows taken at Intervals of 5 seconds (lower tracing). Wet swallows cause a decrease in the frequency of spontaneous contractions. (6) Motility tracing showing frequent spontaneous contractions at 2 and 7 cm above the LES evoked by cholinergic stimulation with bethanechol in a patient with simultaneous contractions (group A). It shows control periods without swallows and periods during which 10 wet swallows were taken at intervals of 5 seconds. Swallows did not seem to have any inhibitory effect on the frequency of the spontaneous contractions.

SWALLOWS

a significant

swallow-induced

CONTRACTIONS

CONTROL

A

: :

OF SIMULTANEOUS

:

S

decrease in the force of both

and spontaneous esophageal contrac-

tions. It decreased the force of the spontaneous

con-

tractions from 65 + 12 to 22 +- 11 mmHg (P < 0.05). It also resulted in a significant decrease in the number of spontaneous contractions (Figure 6) from 12 + 5 contractions to 4 -t 1 contractions per 10 minutes (P <

0.01).

Discudon The results of these studies suggest possible mechanisms that may contribute to the genesis of

S

SWALLOWS

swallow-induced and spontaneous simultaneous contractions in patients with DES and related motility disorders. Swallow-evoked simultaneous contractions had latencies of 4 seconds or less 2 cm above the LES shorter than the latencies of 5 seconds or longer that precede peristaltic contractions of normal or prolonged duration. Paired swallows taken at 5-second intervals evoked a single contraction after the second swallow in subjects with peristaltic contractions but induced one contraction after each swallow in patients with simultaneous contractions. Ten consecutive swallows taken at 5-second intervals inhibited the

116

BEHAR AND RIANCANI

GASTROENTEROLOGY Vol. 105, No. 1

spontaneous contractions induced by cholinergic stimulation in subjects with peristaltic contractions, but they failed to decrease significantly these contractions in patients with simultaneous contractions. These findings could be explained by a defective inhibition with an intact excitation and, in some instances, the defective inhibition could also be associated with increased net excitation suggested by the increased pressure and duration of the contractions. In contrast, spontaneous contractions could be caused by an abnormal spontaneous release of acetylcholine or to a hypersensitive circular smooth muscle responding to normal and spontaneous acetylcholine discharges because they were abolished or significantly reduced by atropine. Swallow evoked peristaltic sequences are mediated by stimuli that originate in the swallowing center and are transmitted

A

Y

via the vagal efferent nerves. They se-

.

PERISTALTIC

SIMULTANEOUS

Figure 5. Effect of ten consecutive wet SWallOWStaken at 5-second intervals on the number of spontaneous contractions induced by bethanechol in patients with normal peristaltic (control group) and simultaneous contractions (group A). A shows the mean + SE of the number of spontaneous contractions in the no swallow period and during the period when ten swallows were taken (0, no swallows; ?? , 10 swallows). f3 shows the percent inhibition induced by 10 wet SWallows in subjects with peristaltic contractions (82% inhibition) and in group A, which included patients with simultaneous contractions (12% inhibition). *Indicates that the difference in the inhibition between these two groups was significant (P < 0.05) (0, peristaltic; W, simultaneous).

quentially activate the esophageal circular striated muscle directly, and by synapsing with intramural neurons they stimulate the circular smooth muscle.’ Vagal impulses travel at the speed of 6 m/set, reaching the entire length of the esophagus about the same time and activate intramural neuromuscular units within the smooth muscle segment. lo These neurons seem to modify the stimulus to ultimately determine the esophageal gradients, which are characterized by latencies of increasing duration as the contraction approaches the LES. Stimulation of the peripheral end of the cervical vagus nerves in the opossum causes simultaneous contractions in the striated muscle segment that last as long as the stimulus; however, it evokes peristaltic contractions in the smooth muscle segment, which are not qualitatively different from the peristaltic contractions induced by swallows. ” Vagal stimulation, like deglutition, induces an initial inhibition or hyperpolarization of the smooth muscle whose duration increases aborally, followed by a depolarization and contraction that is generated after the stimulus is discontinued.12 Changes in the frequency of vagal stimulation shortens the latency period and may even change the polarity of the contractile response that can cause antiperistaltic contractions. l3 Further increases in the stimulus frequency even generates simultaneous contractions.i4 A period of inhibition preceding the peristaltic wave has also been shown in humans by creating an artificial high pressure zone in the midesophagus by inflating a balloon; swallows evoke an LES-like relaxation of this high-pressure zone followed by a peristaltic contraction. l5 Patients with DES and related motor disorders had simultaneous contractions confined mostly to the distal 1O-cm of the esophagus and peristaltic contractions in the proximal striated esophagus. Although it is conceivable that an abnormal vagal drive is the mechanism of these simultaneous contractions, this hypothesis is difficult to reconcile with the presence of simultaneous contractions only in the smooth muscle segment of esophagus. An abnormal vagal drive should alter the peristaltic sequence in the entire esophagus unless the abnormality is only confined to the dorsal motor nucleus of the vagus that controls peristalsis of the smooth muscle segment. They are more likely to result from an inappropriate response to vagal stimuli by the intramural neural units that innervate the smooth muscle segment of the esophagus. The latency period between the stimulus and the onset of contractions may be determined by the interaction of inhibitory and excitatory influences. Thus

PATHOGENESIS OF SIMULTANEOUS CONTRACTIONS

July 1993

117

Figure 6. Manometric tracing of a patient with spontaneous contractions before (control period) and 15 minutes after the administration of atropine. Atropine decreased the frequency of the spontaneous contractions.

short latencies associated with simultaneous tions could be caused by defective inhibition, or premature

discharge

ters, or both. tractions

Increased

of higher

of excitatory excitation

force

gus of subjects

contracincreased

with

should

lead to con-

and duration.

only

However,

in

peristaltic

sequence

at intervals

of 5 seconds

sequences

taken at intervals have been

interpreted

inhibition

evoked

in patients of group B the contractions were peristaltic despite of being prolonged and forceful. These find-

supported

ings

second

of the patients

contractions

of group

had normal

are not consistent

creased

excitation

pressures

with

simultaneous

and duration,

the hypothesis

that

in-

is the major or only cause of prema-

ture simultaneous by the motor

A, their

contractions.

effects

induced

It is also not supported by cholinergic

stimula-

tions

swallow;

inhibitory where

phase is shorter

they do not occur

with

fluences

evoked

the speed of peristalsis

shortening

by swallows

contractions.

of the latency

without

Bethanechol

with

but without

in-

abolishing

the

gradient (Behar J, Unpublished observations). Atropine seems to elicit the opposite effect but without erasing however, caused shorter

the

latency

show forceful latencies

gradient.

in the

Gidda

opossum

that

and

Buyninski,

physostigmine

and prolonged contractions with that even became simultaneous.16

always

and

take place after the

ond swallow. tions,

after each swallow

to the first swallow

the esophagus

after each swallow 5-second intervals. Moreover,

with

of

at inter-

responds

with

of the contracprecedes

simultaneous

the seccontrac-

seems to be the most likely cause responded

when paired

consistent

reason responded

taken

that the onset

In patients

short latencies

of why

peristalsis

and (3) the esophagus

provided

tion in response

than at 2 cm above the LES (this is the likely

with swallows

with previous

a contraction were taken at human

These discrepancies could be the result of species differences or differences in the doses and modes of ac-

10 consecutive swallows taken at 5-second elicit one forceful and prolonged peristaltic

tion between physostigmine and bethanechol. Although our findings do not support an abnormal excitation as the cause of simultaneous contractions,

tion only after the last swallow.

they cannot completely exclude it. This hypothesis would imply that hypersensitive intramural neurons respond to vagal stimulation with a premature and simultaneous discharge of acetylcholine throughout the smooth muscle segment. In agreement with previous studies,“-‘” the esopha-

is being contrac-

after the first swal-

with normal

a contraction

vals of 5 seconds); a contraction

a corresponding

by a persistent

low are more likely to occur in normal subjects at 12 and 7 cm above the LES where the latency period or

of peristaltic

contractions

caused

if they are

These results

that (1) esophageal

swallows

why 3 of 10 subjects

simultaneous

as being

swal-

and two sets of

or longer.

(2) contractions

tion of patients with peristaltic contractions. Bethanechol caused an increase in the pressures and duration becoming

after paired

by the first swallow

by the findings

after paired

responded

one after each swallow

of 10 seconds

and

half

contractions

one peristaltic

lows taken

neurotransmit-

with peristaltic

*’In subjects

studies, intervals contracwith nor-

mal peristalsis, cholinergic stimulation generated frequent spontaneous contractions inhibited during the period of 10 deglutitions taken at 5-second intervals. Cholinergic stimulation caused more frequent spontaneous contractions in patients with simultaneous contractions and were not significantly inhibited by repeated swallows. Decreased neural inhibitory influences in the simultaneous contraction group could ex-

BEHAR AND BIANCANI

118

GASTROENTEROLOGY Vol. 105, No. 1

plain the failure of repeated tractions

evoked

sponsible

for the increased

stimulation.

However,

or increased

sensitivity

plain

swallows

by bethanechol

the greater

excitability

decreased

frequency

the failure

swallow

but cannot

inhibitory

As previously and duration

shown,

atropine

reduced

into peristaltic

contractions

pathogenesis.

frequency their

suggesting

that an excess

Atropine,

however, contractions

the present

study

the

as well as

suggests

mechanisms

in the genesis of swallow-induced

neous

spontaneous

and

simultaneous

of 4 seconds

to

decreased

and force.

In summary,

duced

induced

simultaneous

does not seem to contribute

of the spontaneous

duration

ex-

to the

the force

contractions

but it did not transform

their

adequately

reflex.

of the esophageal

stimulation

also excontrac-

to respond

by swallows,20 cholinergic

refractoriness could

in spontaneous

of the esophagus

induced

to cholinergic

muscle

to acetylcholine

tions caused by bethanechol plain

to block the con-

and may also be re-

contractions.

contractions

or less probably

geal inhibition

elicited

different simulta-

Swallow-in-

have short

latencies

due to ineffectual

esopha-

by the deglutition

reflex; spon-

taneous contractions are blocked by atropine suggesting a dysfunction of the cholinergic neurons with a possible dent

abnormal

release

of the deglutition

the esophageal acetylcholine sponse

from

muscle that

indepen-

reflex or a hypersensitivity to small

are not

a normal

of acetylcholine or normal

sufficient

smooth

of

releases

to trigger

of

a re-

muscle.

References Bennet JR, Hen&ix TR. Diffuse esophageal spasm: a disorder with more than one cause. Gastroenterology 1970;59:273279. Creamer B, Donoghue FE, Code CF. Pattern of esophageal motility in diffuse spasm. Gastroenterology 1958;34:782-796. Vantrappen G, Janssens HO, Hellemans J, Coremans G. Achalasia, diffuse esophageal spasm and related motility disorders. Gastroenterology 1979;76:450-457.

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