Human upper esophageal sphincter

0016-5085/78/7662-0268$02.00/O GASTROENTJWMGY X5268-214, 1978 Copyright 0 1978by theAmerican Gastroentemlogical Association

HUMAN UPPER ESOPHAGEAL

Vol. 75,No.2

Printed in U.SA.

SPHINCTER

Response to volume, osmotic, and acid stimuli DONALD C. GERHARDT, M.D., TIMOTHY J. SHUCK, B.S., RONALD A. BORDEAUX, M.D., AND DANIEL H. WINSHIP, M.D. Department of Medicine, The Harry S. Truman Memorial Medical Center, Columbia, Missouri

Veterans Hospital and the University of Missouri

Upper esophageal sphincter responses to stimuli of intraesophageal infusion were studied in 9 normal human subjects. Upper esophageal sphincter pressures were measured utilizing a water-perfused multilumen catheter with radially oriented pressure-recording orifices. The central core of the catheter opened distally for infusion of test solutions. The six test solutions (distilled water, 0.9% NaCl, 1.8% NaCl, 3.6% NaCl, 0.1 N HCl, 0.2 N HCl) and sham infusion were administered in a randomized double blind manner on 3 to 9 different days in each subject. Tracings were read and data calculated before the code was broken. Infusion with all solutions increased upper esophageal sphincter resting pressure above sham. The upper esophageal sphincter thus responds to the presence of intraesophageal fluid, a volume response. Pressures during 0.1 N HCl infusion were greater than those during 0.9% NaCl infusion, which demonstrates that the upper esophageal sphincter responds to an acid stimulus. Any pressure response to solutions of varying osmolalities was indistinguishable from the volume effect alone in 6 subjects studied. Upper esophageal sphincter pressures were increased further by increases in the rate of infusion of 0.1 N HCl in the upper esophagus in 7 subjects studied. In addition, the closer to the upper esophageal sphincter the infusion was administered, the greater was the pressure response. The onset of the upper esophageal sphincter response to the presence of intraluminal fluid occurred at a mean time of 2.7 set after the initiation of a bolus injection into the esophagus in 4 subjects studied. The mean duration of the upper esophageal sphincter pressure elevation, after cessation of the bolus injection, was 33.5 sec. We suggest that the human upper esophageal sphincter functions as a dynamic barrier to esophagealpharyngeal reflux and possil_le subsequent tracheobronchial aspiration. The upper esophageal sphincter (UES) consists of the cricopharyngeus muscle and possibly a small portion of the circular muscle fibers of the esophagus immediately distal to it.lm5 The UES may serve several important physiological functions. Among those which have been suggested are the prevention of esophageal distention during respiration,2 and the protection against esophageal-pharyngeal reflux and aspiration.6 Hunt et al., for example, reported that UES resting pressures in patients with reflux esophagitis were higher than in normal persons. They suggested that this increase in resting pressure was a response to the presence of ReceivedSeptember12, 1977.AcceptedFebruary22, 1978. Address requests for reprints to: Daniel H. Winship, M.D., Departmentof Medicine,Universityof MissouriMedicalCenter,807 StadiumRoad, Columbia,Missouri 65201. The authors thank John E. Hewett, Ph.D., and Melvin L. Moeschberger, Ph.D., for help with statistical analysis, and Ms. Judy Wilson, Ms. DebbieWilson, Ms. LeeAnnMoore,and Ms. Linda Hucker for assistancewith the manuscript. 268

irritant material in the lower esophagus and prevented reflux into the pharynx.6 Stanciu and Bennett,’ however, found no difference in UES pressures between normal persons and patients with gastroesophageal reflux. Further, they reported that the UES did not respond with increased resting pressure to the stimulus of acid within the esophagus. Creamer and Schlegel* reported that the UES did respond with increased pressure to intraluminal distention by balloon or by rapid injections of boluses of water, although this response was inconstant. Our study was designed to answer the question whether the UES responds with increased resting pressure to a variety of intraesophageal stimuli; that is, is the response such that the UES might function as a dynamic barrier to esophageal-pharyngeal reflux? Is the only response one to intraesophageal volume, or distention, or does the UES respond to acid stimuli or changes in osmolality as well? Does the location of the fluid stimulus within the esophagus influence the response?

August

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Methods Subjects. Nine normal volunteers were studied. None had any history or symptoms of prior esophageal disease. Six were female and 3 were male, ages 21 to 28 (mean 24) years. All subjects gave voluntary informed consent. This study was approved by the combined Human Experimentation Committee of the Truman Veterans Administration Hospital and the University of Missouri Medical Center. Recording catheters. Two six-lumen catheters, oval in cross section (catheter diameter, 4.5 by 6.6 mm; internal diameter of each lumen, 0.8 mm; fig. 1) and a round nine-lumen catheter (catheter diameter, 6.0 mm; internal diameter of central core, 1.6 mm; internal diameter of each of eight lumens, 0.8 mm; fig. 2) were constructed with polyvinyl tubing (Pharmaseal, Glendale, Calif.) fused longitudinally with tetrahydrofuran. For the six-lumen catheters, the four side opening orifices for manometric recording were radially oriented at 90” angles, all at the same cross sectional level (fig. 1). The two central tubes were used as the core for construction of the oval shape and they opened distal to the recording orifices. The test solutions were infused through these central tubes. On one catheter, the central tubes opened 10 cm distal, and on the second catheter, they opened at 5 and at 15 cm distal to the recording orifices. The oval shape of the catheter conformed to the anatomical configuration of the esophageal lumen at the UES which is, at rest, a somewhat curved transverse slit, longer in the transverse diameter than in the anterior-posterior dimension.’ The catheter’s cross sectional shape therefore facilitated maintenance of the catheter orientation, such that the orifices would lie posteriorly, anteriorly, and laterally throughout the pullthrough studies. The posterior tube of the catheter was colorcoded black so that the position could be frequently monitored visually. The nine-lumen catheter (fig. 2) with the larger central core was used for injections of fluid boIuses into the esophagus. Three orifices were at the same cross sectional level 90” apart for UES measurement, directed posteriorly, anteriorly, and laterally. One orifice was 3 cm above this level for recording pharyngeal pressures, and the other orifices opened 5, 10, and 20 cm distally. The central tube opened 15 cm distal to the three radial UES orifices. The posterior tube of the catheter was color-coded. Instruments. A pneumohydraulic capillary infusion system (Arndorfer Medical Specialties, Greenfield, Wis.) was used for continuous infusion through the manometric lumens. Water, twice boiled to remove dissolved gases, was infused at 0.5 ml per min through each of the lumens. Each pressure catheter 1 P

L

L

R

A FIG. 1. Cross section of the six-lumen polyvinyl catheter at the level of the manometric orifices. P, posterior; A, anterior; R, right; and L, left (manometric orifices). I,internal core tubes (for infusion of test solutions).

1

L

3cm

5cm

I---

5cm

-I

5cm

r

5cm

FIG. 2.Round, nine-lumen polyvinyl catheter. Three lumens are at the same cross sectional level for upper esophageal sphincter (UES) pressure recordings; P, posterior; A, anterior; R, right. The other recording orifices are located at 5,10, and 20cm distal to UES orifices. The infusion orifice (I)is located 15 cm distal to the UESrecording orifices. The pharyngeal pressure-recording orifice is 3 cm proximal to UES orifices. TABLE 1. Test

solution

Distilled water 0.9% NaCl 1.8% NaCl 3.6% NaCl 0.1 N HCl 0.2 N HCl

Osmolalitv and pH of test solutions Osmolality PH milli0smoleslkg <24 5.60 287 5.62 563 5.73 1105 5.75 242 1.00 497 0.73 I

was connected to a Hewlett-Packard Transducer model 1280C (Hewlett-Packard Midwest Region, Maryland Heights, MO.); an eight-channel Hewlett-Packard recorder model 7788A, calibrated in mm Hg before each use, was used for pressure recording. The compliance of our recording system, including the manometric catheter,was sufficiently low to record high and rapidly changing pressures in the UES CAP/AT > 400 mm Hg per set). *I1 Intraesophageal infusions of the test solutions were performed with a Harvard compact infusion pump model 975 (Harvard Apparatus Co., Inc., Millis, Mass.). Respiration and swallowing were monitored with two belt pneumographs (Hewlett-Packard model 108) placed around the chest and neck, respectively. The pneumographs were connected by a Ytube to a Hewlett-Packard air transducer model 270, which in turn was connected to the recorder. Test solutions. Six solutions were prepared and coded. The osmolality and pH of each solution were measured by osmometry (Advanced Instruments osmometer model 3L, Advanced Instruments, Inc., Newton Highlands, Mass.) and by glass electrode (Beckman Expandomatic SS-2 pH meter, Beckman Instruments, Inc., Fullerton, Calif.), respectively. The data are shown in table 1. Study plan-phase I, ZZ, and 111. The subjects were fasted for at least 6 hr before the study. No topical anesthesia or other medications were used. Each subject was intubated by mouth with one of the oval tubes. The subject was then placed in a supine position, and the manometric transducers were adjusted to the midaxillary line. The color-coded tube of the catheter was positioned posteriorly and was frequently monitored visually. The other UES manometric orifices thus were positioned to the subject’s left, anterior, and right. They were observed to be maintained in those positions throughout the studies. The coded solutions and a sham (control) were administered in a randomized sequence in a double blind fashion. One of the investigators changed the coded test solutions. Neither the other investigator (operator) nor the subject was told which solution was being infused. The sham was handled precisely the same as the test solutions with the exception that, unknown to the operator or patient, the infusion catheter was disconnected from the syringe and pump.

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GERHARDT

A base-line pull-through to locate the position of the sphincter was done on each study day in each subject. After this preliminary pull-through, the tube was positioned such that the recording orifices were at the distal margin of the UES. The first test solution (or sham) was then infused into the esophagus distal to the manometric orifices for 3 min before the next pull-through and was continued throughout the pullthrough. The 5 cm pull-through of the UES was performed in 0.5-cm increments, with a swallow at each station and with a 10 to 15-set pause after each swallow complex to obtain a resting pressure. Ten pressure measurements were thus recorded from each orifice per pull-through. After the pullthrough, the catheter was advanced to its original location and the next infusion was carried out in precisely the same fashion. Phase I. This portion of the study was designed to determine the effects of intraluminal volume and acid stimuli on the UES resting pressure. Nine subjects received sham, 0.9% NaCl, and 0.1 N HCl infusions. Six of the subjects also received an infusion with 0.2 N HCl. Each subject had six pull-throughs of the UES per day on 3 to 9 different days. The order of administration of the test solutions and sham was rotated every day such that each occupied a different position in the infusion sequence on the separate study days. The infusion rate of the test solutions was 11.0 ml per minute, and approximately 55 ml of each solution was administered per pull-through. The location of infusion was 10 cm distal to the UES at the start and was 5 cm distal at the end of the pull-through. Phase ZZ. The purpose of this portion of the study was to investigate the effects of changes in osmolality of the infusion fluids on upper esophageal sphincter resting pressure. Six of the subjects received sham, distilled water, 0.9% NaCl, 1.8% NaCl, and .3.6% NaCl. Each of the subjects received five infusions per day for 3 days. The order of administration of test solutions and sham was again rotated every day. Each test solution occupied a different position in the infusion sequence on separate study days. The location and the rate of the infusion were the same as in phase I. Phase ZZZ.The purpose of this portion of the study was to ascertain whether rate of fluid infusion or the location at which it was infused into the esophagus were important determinants of UES resting pressure. Seven of the subjects received infusions of 0.1 N HCl on 3 separate days. These infusions were initiated at 5 or 15 cm distal to the UES; the rates used in addition to sham (0 ml per minute) were 5.5, 11.0, and 22.0 ml per min. The pull-throughs of the UES were otherwise performed in the same manner as in phases I and II. Study plan-phase IV. This portion of the study was designed to determine the temporal characteristics of the UES pressure response to intraluminal fluid infusion. Four subjects were studied, 2 of them on 2 days each, and 2 on 1 day each. In all, 25 bolus injections were performed on the 6 days. The preparation of the subjects, intubation, positioning, and transducer adjustments were carried out as described for phases I through III, except that the round, nine-lumen catheter was used in this part of the study rather than the oval catheter. The color-coded tube was positioned posteriorly. After a preliminary pull-through for location of the UES, the three UES manometric orifices were placed at the level of the peak UES pressure and held in place for the subsequent bolus injection studies. The 0.9% NaCl solution was infused as a bolus of 50 ml over 5 to 10 sec. It was infused through the large central core tube of the catheter into the esophagus, 15 cm distal to the UES. The start and completion of the injection of the fluid was

ET AL.

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recorded on the tracings so that the onset and duration of UES response could be calculated. The catheter utilized in this phase of the study had openings proximal and distal to the UES-recording level. These pressure orifices permitted the monitoring of pressure changes in the pharynx and body of the esophagus.

Analysis of Records Phases I, ZZ, and ZZZ. The manometric records were read and the data were calculated by the blinded investigator before the code was broken. A mean of the highest resting pressures, taken at approximately the middle of the rhythmic respiratory fluctuations, and excluding the swallowing complex, was tabulated for each 0.5-cm increment of the UES pull-through. This tabulation was made for each of the radially oriented orifices. Atmospheric pressure was taken as zero. Phase IV. Simple analyses were made. These consisted of (1) the determination of a UES pressure response, (2) the recording of the time lapsed from onset of bolus injection to the point at which a sustained increase in UES pressure above resting pressure occurred, and (3) the calculation of the time lapsed from cessation of bolus injection to the return of the UES pressure to the preinjection level. Statistical analysis. Nonparametric methods were used for the statistical analysis. A mean peak pressure for each subject was obtained for a given type of infusion carried out during each phase. The Wilcoxon signed rank test was used to determine the significance of differences between these mean peak pressures for each paired treatment.” A P value of 0.05 or less was accepted as denoting statistical significance.

Results The length of the UES high pressure from 3 to 4 cm in our subjects. The distal UES was located between 16 and 20 proximal margin was 12 to 16 cm from the

zone ranged margin of the cm, and the

incisor teeth. The relationship of the pressures registered at each recording orifice to that of the other orifices was analyzed (table 2). The mean peak posterior pressure was higher than the anterior for all infusions (P < 0.002). Both the posterior and anterior mean peak pressures were substantially higher than the peak pressures at the lateral orifices (posterior, P < 0.001; anterior, P -=c

O.OOl), but the pressures recorded at the lateral orifices were not significantly different from each other (P > 0.1). Further analysis was carried out to assess the influence of position in the sequence of infusions of the test solutions on the amplitude of the UES resting pressures for a given infusion. No significant influence of position in the sequence of infusion on the UES resting pressure TABLE 2. Peak upper esophageal sphincter CUES) pressure

response

to sham, saline, and acid infusions Solution Sham

0.9% NaCl 0.1 N HCl

Recording orifice orientation Po&rior

109 L 4” 127 r 5 138 ? 6

Anterior

Left

Right

88 5 4

48 f 2

98 2 4 108 r 5

60 2 2 65 2 3

45 ‘- 2 54 t 2 61 2 3

u Mean pressure (mm Hg 2 SEM) for 9 subjects on 3 to 9 study days. These values were derived from the mean peak pressure from each subject for each orifice for each solution.

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ESOPHAGEAL

SPHINCTER

RESI ‘ONSE

was identified for any solution or for any position in the sequence. Effects of intraluminal volume and acid stimuli: phase I. The mean peak UES resting pressure after 0.9% NaCl infusion was significantly higher than the value for sham infusion, regardless of recording orifice orientation (tables 2 and 3-posterior, P < 0.01; anterior, P < 0.025; left, P < 0.01; right, P < 0.005). Similarly, the mean peak pressure recorded during 0.1 N HCl infusion was greater than that observed during 0.9% NaCl infusion (posterior, P < 0.010; anterior, P < 0.010; left, P < 0.025; right, P < 0.005). Figure 3 depicts an actual series of pressure tracings from 1 subject during 1 study day. The differences between the UES resting pressures in this sequence, acid > saline > sham. may be clearly appreciated. In the 6 subjects studied with 0.2 N HCl infusion, the stronger acid did not further increase the resting UES pressure above that observed with 0.1 N HCl (P > 0.3). TABLE 3. Peak upper esophageal

sphincter CUES) pressure response

to sham, saline, and acid infuscons (posterior orientation) ._ Subject

Study days

J. B.

9

TO INTRALUMINAL

Effects of infusion fluid osmolality: phase II. Analysis of the mean peak UES pressures, from all four orifice orientations, in the 6 subjects who received sham, distilled water, 0.9% NaCl, 1.8% NaCl, and 3.6% NaCl revealed the following (table 4): (1) All fluid infusions resulted in peak UES pressures greater than those observed with sham infusion (P < 0.05, combining all oriented pressure recordings). (2) No difference was appreciated between the UES pressures registered during infusions of the distilled water or saline solutions (P > 0.1). Effects of infu%on rate and intraesophageal location of infusion: phase IZZ. Figure 4 depicts the mean peak UES pressures registered from the posteriorly oriented orifice during studies in the 7 subjects in whom the investigations of infusion rate and location were carried out. The solid line represents a response for the set of infusion rates of 0.1 N HCl (sham or 0, 5.5, 11.0, 22.0 ml per minute) at the more proximal study location within the esophagus (5 cm distal to the UES). Each increase in the infusion rate resulted in an increase in the UES resting pressure through all rates tested. This dose

Solution

Sham

93

k

-

8”

0.9% N&l

0.1 N HCl

119 + 9

118 t 12

T. K.

9

135 2 12

149 k 17

170 2 15

J. R.

9

98 t 5

114 2 14

123 -c 16

TABLE 4. Peak upper esophageal

sphincter CUES/ pressure response to changes in osmolality

Solution

C. T.

9

106 k 6

118 f 5

127 t 7

J. H.

9

137 I 5

156 + 10

164 -t 11

Sham

T. H.

6

142 t 21

143 ? 21

180 i 30

K. C.

3 3 3

67 t 6

86 2 4

93 2 5

Water 0.9% NaCl 1.8% NaCl 3.6% NaCl

W. B. C. F. Mean

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PERFUSION

121 i

10

124 k 17

134 IT 22

91 -t 3

87 2 3

83 2 4

109 2 4

127 lr 5

138 i- 6

fl Mean pressure (mm Hg ?

SEM)

for all study days.

Recording orifice orientation Posterior 96 -t 10”

106 106 109 105

-c t +f

14 12 10 11

Anterior

Left

Right

76 -t 13

43 t 4

41 ‘- 5

83 83 91 84

48 51 49 46

45 47 46 46

t + -t 2

13 12 12 10

? t r I

5 3 4 4

-c 2 -t -t

--

5 5 6 6

u Mean pressure (mm Hg t SEMI for 6 subjects on 3 study days. These values were derived from the mean peak pressure from each subject for each orifice for each solution.

FIG. 3. Actual series of upper esophageal sphincter CUES) pressure recordings from 1 subject on 1 study day. A represents the sham infusion; B, the infusion with 0.9% NaCl, and C, the infusion with 0.1 N HCl (all at a rate of 11 ml per min, infused 10 cm distal to UES). Intraluminal pressures are recorded in mm Hg with a six-lumen oval catheter. All manometric orifices are at the same cross sectional level. The distance of the recording orifices from the incisors is listed, in cm, at the bottom of the tracing. S, swallow; P, posterior; L, left; A, anterior, and R, right (recording orifice orientation). Resp, respirations, are recorded at the bottom of each tracing. The paper speed is 2.5 mm per sec.

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response is demonstrated by the significant differences between pressures at rates of 0 and 11.0 ml per min (P < 0.05) and 0 and 22.0 ml per min (P > 0.01). With regard to the distal infusion position (fig. 4, dushed line, 15 cm distal to the UES), a significant difference in pressure response to changes in rate was appreciated only when the infusion rate reached 22.0 ml per min (P < 0.05). Analysis of the values from the other recording orifice orientations yielded similar results. Furthermore, the closer the acid was infused to the UES, the greater was the response (P < 0.05) for the ll.O-ml per min rate.

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ET AL.

A series of UES pressure tracings from 1 subject on 1 study day is shown in figure 5. The increased pressure response to increasing infusion rates is clearly demonstrated. Effects of bolus injection: phase IV. Bolus injection of 0.9% NaCl (50 ml over 5 to 10 set) into the esophagus 15 cm distal to the UES resulted in a sudden marked increase in UES pressure in 24 of 25 injections (96%). The time from the beginning of the bolus injection to the onset of the sharp intraluminal pressure increase of the UES was 2.7 + 0.3 sec. The time interval from cessation of injection to return of the pressure to the preinjection level was 33.5 & 5.7 sec. This pattern of response in the UES was observed in all directionally oriented manometric orifices. Pressures monitored in the pharynx and body of the esophagus during bolus injection contirmed that the UES pressure increase soon after injection was not related to a swallow nor was it a part of a secondary peristaltic wave. Discussion

100

”

If 1

0

(SHAM)

6.

lb

1;

RATE

(ml/min)

io

;5

FIG. 4. Response of the upper esophageal sphincter (UES) (posterior recording orifice) to changes in rate and location of intraesophageal infusion of 0.1 N HCl. The solid line represents infusion 5 cm distal to the UES. The dashed line represents infusion 15 cm distal to the UES. The points on the graph represent the mean + SEM for 7 subjects tested.

An important obstacle to the investigation of the UES has been the marked variation and apparent lack of reproducibility of the recorded intraluminal pressures. Rinaldo and Levy’” noted this marked variation. Winans4 correlated the anatomy of the pharyngeal-esophageal junction to the observed pressure profile. He showed that the pressure recorded from within the pharyngeal-esophageal high pressure zone depended upon the directional orientation of the recording orifice within the lumen. The fact that this orientation of the pressure-detecting orifice was not monitored in other previous studiesw adds to the confusion brought about by attempting to interpret the data from these studies. Another factor which contributes to the lack of consistency in UES studies has been the lack of satisfactory recording systems. It is now known that high amplitude and rapidly changing pressures are underestimated by the standard high compliance infusion systems, but

FIG. 5. Actual series of upper esophageal sphincter (UES) pressure recordings from 1 subject on infusion; B, the infusion of 0.1 N HCl at 5.5 ml per min; C, the infusion of 0.1 N HCl at 22.0 ml per min Intraluminal pressures are recorded in mm Hg with a six-lumen oval catheter. All manometric orifices The distance of the recording orifices from the incisors is listed, in cm, at the bottom of the tracings. anterior; and R, right (recording orifice orientation). Paper speed is 2.5 mm per sec.

1 study day. A (all are infused are at the same S, swallow; P,

represents the sham 5 cm distal to UES). cross sectional level. posterior; L, left; A,

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UPPER ESOPHAGEAL SPHINCTER RESPONSE TO INTRALUMINAL PERFUSION

that the compliance of a system can be greatly reduced by a hydraulic infusion pump.+” A small lumen catheter such as ours (0.8 mm internal diameter) also decreases compliance because compliance is inversely related to lumen size.‘O, I1To ensure recording accuracy of pressures occurring in the cervical esophagus, the pressure rate rise, APIAT, should be z 300 mm Hg per sec.“’ The performance charactristics of our system yield APl AT > 400 mm Hg per set which is well above this accepted range. Our interest in carrying out these investigations of UES function was stimulated by the conflicting reports in the literature concerning the UES, as well as by the technological advances which have made high fidelity recording systems available to record UES pressures accurately. We therefore utilized the oval catheter in order to control the directional recording of the UES intraluminal pressures. By monitoring the catheter orientation we determined that the oval catheter did not rotate during the studies. We also employed a high fidelity manometric recording system to register these pressures accurately. With these techniques, we have shown that the UES responds with increased resting pressure to the intraesophageal infusion of fluid. Our results are similar to those of Winans4 in that pressures in the posterior-anterior direction were always higher than lateral pressures from the UES. Results in our study differ from those of Winans, however, in that we found posterior pressures to be significantly higher than anterior pressures. We recognize several possible reasons for this posterior-anterior pressure differential. It is conceivable, for example, that the pressure difference is related to the performance of the manometry with the subjects supine, inasmuch as the posterior orifice would be more dependent than the anterior one. This explanation seems unlikely, however, because perusal of our tracings of pressures recorded from the body of the esophagus (unpublished obserzlations) revealed no such differences in posterior and anterior orifice orientation pressures. It is also possible that posterior pressures were higher than anterior because the contracting cricopharyngeus muscle might cause the posterior orifice to be sealed more effectively than the more rigid anterior cartilage-supported surface. The lateral pressures in our study were higher than those recorded by Winans.l This difference may be related to our use of the oval-shaped catheter. It has been shown for the lower esophageal sphincter14* I5 and the UES’” that catheter diameter influences resting yield pressures. We postulate that our oval catheter permits a better sealing of lateral recording orifices than a round catheter in the UES, thus giving rise to higher recorded yield pressures. We have identified several characteristics of the perfusing fluid important to the UES response. First, the UES responds to the stimulus of intraesophageal volume, as was recognized by other investigators who utilized bolus injection@ and balloon distentions.x, ItiWe have demonstrated that this response of the UES also occurred with a continuous infusion of 0.9% NaCl at a

273

low rate of 11.0 ml per min in the midesophagus (10 cm distal to UES), but not with sham infusion. Second, the UES responds to an intraluminal acid stimulus to a degree greater than can be explained by its volume effect alone. Thus, a greater UES pressure response occurred to 0.1 N HCl than to 0.9% NaCl. By increasing the acid concentration to 0.2 N HCl, we observed no further increase in UES pressures. These results, however, are at variance with those of Stanciu and Bennett,7 who were unable to show increased UES pressure in human subjects upon perfusion of the esophagus with acid. Frieman and Diamant17 showed that intraesophageal perfusion of acid increased UES pressure in dogs, but these investigators did not separate this acid response from a volume response, which they might have done by using a solution such as 0.9% NaCl as a control. Third, UES pressures were not altered by changes in osmolality of the infusing fluid during short term infusions. Any response to solutions of varying osmolalities was indistinguishable from the volume effect alone. Fourth, the UES pressure response to intraesophageal infusions of 0.1 N HCl was dose dependent. Acid delivered at increasing rates into the esophagus evoked incremental increases in the UES resting pressure. The decreasing slope of the curve above 11.0 ml per min rate (at 5 cm from the UES) suggested a saturable response rather than an all-or-none response. Further, we have confirmed in human beings a finding previously demonstrated in dogs,” that the closer to the UES the infusion was administered, the greater was the response . We cannot exclude the possible contribution of the presence of acid in the stomach to UES pressures. We did not specifically examine this possibility, but our data show that the further from the UES that the fluid was infused (i.e., 15 compared to 5 cm), the less was the response. This observation suggests that any possible effect of the presence of acid in the stomach on UES pressures is far outweighed by the effects arising from the esophagus. We have demonstrated that the UES responds to an amount of 0.1 N HCl as small as 5.5 ml per min, provided it is infused in the upper one-third of the esophagus. Fifth, the onset of the UES response to the presence of intraluminal fluid was very rapid, at least as demonstrated during bolus injections. The mean time lapse of 2.7 set between onset of bolus injection and UES response observed in our study compares favorably with the 2.4-set lapse from injection to peak response reported in prior bolus studies.H The mean duration of the increase of UES pressure over its resting base line, after stopping bolus injection, was 33.5 sec. The UES responded with an increase in pressure in 96%’ of the instances of bolus injection. This was a higher incidence of response than the 42% incidence reported by others.# In all instances the pressure returned to preinjection levels within ll/z min of stopping the fluid injection. These results support our belief that in our study the 3min infusion of the test solution before the pull-through is sufficient to allow the UES response to occur as well

274

GERHARDT ET AL.

as to permit resolution of the response which has been developed to the infusion of the preceding test solution. The fact that this response is very rapid suggests that the mediator of the response is either neural or a local reaction. Hormonal control appears unlikely. It has been suggested that the response of the UES to acid infusion in dogs is mediated by way of the vagosympathetic trunks, because bilateral nerve blockade caused a reduction in the maximum response to acid.” We believe that the UES response with increased resting pressure to intraesophageal fluid, especially acid, is probably of physiological importance. That is, the UES in man probably serves as a dynamic barrier to esophageal-pharyngeal reflux, and thereby protects against trachea-bronchial aspiration. REFERENCES 1. Ingelfinger FJ: Esophageal motility. Physiol Rev 38:533-584, 1958 2. Palmer ED: Disorders of the cricopharyngeus muscle: a review. Gastroenterology 71:510-519, 1976 3. Ellis FH: Upper esophageal sphincter in health and disease. Surg Clin North Am 51:553-565, 1971 4. Winans CS: The pharyngoesophageal closure mechanism: a manometric study. Gastroenterology 63:768-777, 1972 5. Code CF, Schlegel JF: Motor action of the esophagus and its sphincters. In Handbook of Physiology, sect 6: Alimentary Canal, vol 4. Edited by CF Code. Washington DC, American Physiological Society, 1968, p 1821-1839

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6. Hunt PS, Connell AM, Smiley TB: The cricopharyngeal sphincter in gastric reflux. Gut 11:303-306, 1970 7. Stanciu C, Bennett JR: Upper esophageal sphincter yield pressure in normal subjects and in patients with gastroesophageal reflux. Thorax 29:459-462, 1974 8. Creamer B, Schlegel J: Motor responses of the esophagus to distention. J Appl Physiol 10:498-504, 1957 9. Dodds WJ, Stef JJ, Hogan WJ: Factors determining pressure measurement accuracy by intraluminal esophageal manometry. Gastroenterology 70:117-123, 1976 10. Dodds WJ: Instrumentation and methods for intraluminal esophageal manometry. Arch Intern Med 136:515-523, 1976 11. Arndorfer RC, Stef JJ, Dodds WJ, et al: Improved infusion system for intraluminal esophageal manometry. Gastroenterology 73123-27, 1977 12. Conover WJ: Practical non-parametric statistics. First edition. New York, John Wiley & Sons, Inc. 1971, 206-216 13. Rinaldo JA, Levy JF: Correlation of several methods for recording esophageal sphincteral pressures. Am J Dig Dis 13:882-890, 1968 14. Kay MD, Showalter JP: Measurement of pressure in the lower esophageal sphincter: the influence of catheter diameter. Am J Dig Dis 19:860-863, 1974 15. Lydon SB, Dodds WJ, Hogan WJ, et al: The effect of manometric assembly diameter on intraluminal esophageal pressure recording. Am J Dig Dis 20:968-970, 1975 16. Enzman DR, Harrell GS, Zboralske FF: Upper esophageal responses to intraluminal distention in man. Gastroenterology 72:1292-1298, 1977 17. Frieman JM, Diamant NE: Upper esophageal sphincter response to esophageal distention and acid, and its alteration with nerve blockade (abstr). Gastroenterology 70:970, 1976