Videoradiographic, manometric, and electromyographic analysis of canine upper esophageal sphincter IVAN M. LANG, ROBERTO 0. DANTAS, IAN J. COOK, AND WYLIE J. DODDS Departments of Surgery, Medicine, and Radiology, Medical College of Wisconsin, Milwaukee 53226; and Zablocki Veterans Administration Medical Center, Milwaukee, Wisconsin 53295

IVAN M., ROBERTO 0. DANTAS, IAN J. COOK, AND J. DODDS. Videoradiographic, manometric, and electromyographic analysis of canine upper esophageal sphincter. Am. J. Physiol. 260 (Gastrointest. Liver Physiol. 23): G911-G919, 1991.-We assessed upper esophageal sphincter (UES) function in dogs by concurrent recording of cricopharyngeal electromyographic (EMG) activity, intraluminal pressure, and dimensional changes of the pharyngoesophageal junction at rest and during swallowing. Radial and axial pressure profiles of the UES were determined by continuous pull-through manometry. EMG activity of the cricopharyngeus and thyropharyngeus muscles were correlated with UES pressure under static conditions. We also quantified the temporal relationships among EMG activity of the cricopharyngeus, UES pressure, and pharyngoesophageal junction dimensional changes during swallowing of 2,4, and 6 ml of barium. When the dogs were prone, the anterior and posterior UES pressures were about twice the lateral pressures and the axial length of the UES was -4 cm. All radial pressures equalized to -20 mmHg when the dogs lay on their sides. The peak pressure zone of the UES corresponded closely with the level of the cricopharyngeal electrode, and resting UES pressure correlated closely with cricopharyngeal but not thyropharyngeal EMG activity. During swallowing, the cricopharyngeus relaxed -200 ms before UES opening and 100 ms before UES relaxation. Superior movement of the hyoid and the larynx was associated temporally with UES relaxation, while anterior movement was associated with UES opening. Increases in bolus volume significantly increased maximal sagittal UES diameter during UES opening but did not alter temporal changes in UES function. We concluded that 1) the cricopharyngeus is the main muscle of the UES during static conditions, 2) cricopharyngeal tone is continuous but not constant and is dependent on posture, 3) the magnitude of UES pressure correlates closely with the underlying EMG activity of the cricopharyngeus muscle, and 4) the thyrohyoideus may be the main muscle that retracts the UES anteriorly during swallowing. LANG, WYLIE

swallowing;

cricopharyngeus;

thyropharyngeus;

thyrohyoideus

UPPER ESOPHAGEAL SPHINCTER (UES) serves as a gateway between the pharynx and esophagus. This sphincter normally remains closed to prevent aspiration of esophageal contents, but it opens briefly to allow the passageof gas, liquids, or solids during swallowing, belching, regurgitation, or vomiting. UES function has been investigated using three different techniques: electromyography of the cricopharyngeus muscle (8, 11, 18, 21, 24, 26, 28), intraluminal manometry (6, 12, 14, 17, 23, 29), and dimensional analysis of pharyngeal structures THE

using cineradiography or videofluoroscopy (6,12,14, 17). Each technique, however, measures a different aspect of sphincteric function. Electromyography provides a good measure of the timing and magnitude of sphincteric muscle activation, but electromyography does not determine the resultant effects of muscle activity on intraluminal pressure or sphincter patency. Videoradiography determines the patency of the sphincter and the position of structures, such as the hyoid and larynx, but does not determine the forces that regulate UES function. Intraluminal manometry records the resultant force vector generated by various muscles and other factors (e.g., bolus pressure) but does not determine the sources of such forces, nor sphincter patency. In addition, temporal resolution of events recorded by videoradiography and manometry is limited compared with electromyography. Therefore, at present, a complete understanding of UES function cannot be obtained without using all three techniques. Prior studies, however, have not evaluated UES function by all three techniques in the same subjects. Electromyography of the pharyngeal constrictors has been used extensively in animals (3, 8, 18, 21), but human studies have been limited (11, 26, 28, 29) because it is difficult to record from the pharyngeal constrictors during dynamic events like swallowing. Videofluoroscopy (6, 12, 14, 17) and manometry (6, 12, 14, 17, 29) have been used extensively in humans but not in awake animals, because it is difficult to train most animal species to accept a pharyngeal catheter or to remain stationary for video studies. Differences in recording techniques have contributed to different conclusions among investigators regarding the central mechanisms that control UES function during swallowing. From animal electromyograpic studies, researchers (6, 7, 20) have concluded that the timing of pharyngeal muscle activity during swallowing occurs in a stereotypic fashion, controlled by a central pattern generator that is not affected by reflex feedback regulation. On the other hand, in human studies using videofluoroscopy and intraluminal pressure recordings, investigators (7, 8, 23) have observed that the timing of the movement of anatomical structures and UES relaxation is related to bolus size and consistency (6, 14, 17). From this evidence, they have concluded that the brain stem central pattern generator of swallowing is modulated by sensory input. It is difficult to know whether this difference in conclusions is due to species variation, technical G911

Downloaded from www.physiology.org/journal/ajpgi at Glasgow Univ Lib (130.209.006.061) on February 14, 2019.

G912

ANALYSIS

OF

differences, or both, because such studies employed different recording techniques for different species. Our primary objective in this study, therefore, was to record simultaneously electromyographic activity, intraluminal pressure, and dimensional changes of the UES concurrently in dogs. By using these three techniques to assess UES function in the same subjects, we expected to gain a better understanding of 1) the forces that govern UES function, 2) the specific muscle activity that causes the changes in UES function observed by videoradiography and manometry, and 3) the central mechanisms controlling UES function. METHODS

Surgical Preparation

of the Animals

The dog was selected as the animal model because dogs can be trained to lie quietly on a fluoroscopy table and to accept a transoral pharyngeal manometric catheter. Also, the canine cricopharyngeus is a relatively large and well-defined structure suitable for electromyographic recording. We studied 17 animals, 7 of which had electrodes chronically implanted on their cricopharyngeus and thyropharyngeus muscles. Surgery was done during pentobarbital sodium (30 mg/ kg iv) anesthesia using aseptic techniques. After a midline incision on the ventral surface of the neck, the sternohyoid muscle was bluntly dissected along the midline to expose the trachea. Muscles of the lateral wall of the neck were retracted and the pharyngeal constrictors were gently separated from surrounding muscles, taking special care not to disturb their innervation. The cricopharyngeus muscle was identified by its circular fibers that inserted onto the cricoid cartilage and by its lack of median raphe. The slitlike space separating the thyropharyngeus and the cricopharyngeus muscles was identified, and electrode assemblies were sewn onto these muscles (Fig. 1). Wires from the electrodes, connected to a plug, were tunneled subcutaneously to the intrascapu-

FIG. 1. Radiograph and line drawing of pharyngoesophageal junction during a continuous pull-through ma&metric-recording of-peak radial and axial unner esonhaaeal snhincter KJES) nressure. Side holes of the manometric catheter were located just above radiopaque markers. At this frame, the catheter recorded peak posterior UES pressure, and the pressure ports were at the level of cricopharyngeal electrodes.

UES

FUNCTION

lar region, and the plug was brought through the skin. A subcutaneous flange held the plug in place. Experiments were begun a minimum of 10 days after surgery. Electromyography

Implanted bipolar electrodes, consisting of N-gauge silver wires, were embedded in a Silastic rubber backing, spaced 5 mm apart, and exposed for a length of 3 mm. The electrodes were sutured to the muscle oriented along the long axis of the muscle fibers. The electrodes were connected to an Amphenol plug by Teflon-coated wires. The plugs were embedded in a dental acrylic base. For electromyographic recordings, electrical activity was first band-pass filtered (0.1-l kHz) then amplified through Grass AC preamplifiers (model 7P3) and stored on polygraph paper (Grass model 7D polygraph) and tape (Hewlett-Packard instrumentation recorder). Electromyographic activity was later integrated and quantified by playing the taped electromyographic activity through preamplifiers with a time constant of 0.2 s and a highfrequency filter at 3 Hz. Threshold level was set to record zero activity during sphincteric relaxations that occurred during dry swallows. Integrated electromyographic activity provided an overall index of muscle activity that reflected all changes in electrical activity whether due to spatial or temporal summation. Manometry

Two types of manometric catheters were used. The first type was designed for recording radial and axial UES pressures during a continuous pull-through. Six polyvinyl catheters of 0.9 mm in diameter were fused together to form an oval assembly measuring 4 x 7 mm. Four radial recording orifices were cut at the same level separated by a 90” angle. The shape of the manometric assembly, which conformed to the overall oval slope of the pharyngoesophageal region, helped to maintain the position of the assembly in the lumen during the pullthrough and when the animal was moved. Radiopaque markers of different lengths located just distal to each side hole allowed fluoroscopic determination of side-hole orientation. This allowed us to check the proper orientation of the side holes during the experiments. A recording site was also located 5 cm proximal and 5 cm distal to the four radial recording sites. A second manometric assembly was designed to obtain continuous recording of UES pressure during resting conditions and swallows. This assembly was composed of fused Silastic catheters (0.6-1.0 mm in diameter) and incorporated a Dent sleeve device 6 cm in length as described previously (16). The sleeve device allowed continuous recording of UES pressure even when the UES moved axially during swallowing. The sleeve assembly incorporated five sidehole recording sites so that the orifices were located 2 and 0 cm above the proximal sleeve margin and 0, 7.5, and 15 cm below the distal sleeve margin. During recording sessions, each manometric device was perfused with water at a rate of 0.2-0.5 ml/min by a hydraulic-capillary pump (2). Pressure activity was recorded on both the polygraph and on a FM tape recorder (Hewlett-Packard model 3968A).

Downloaded from www.physiology.org/journal/ajpgi at Glasgow Univ Lib (130.209.006.061) on February 14, 2019.

ANALYSIS

OF

Videofluoroscopy Videofluoroscopic imaging was done at 60 keV using an X-ray tube with a focal spot of 0.3 mm in the 6-in. image magnification mode. Video sequences were recorded at 30 frames/s on 0.5-in. videotape using a Beta video recorder (Sony SLHF 900). The videofluoroscopic, manometric, and electromyographic recordings were synchronized using a modified clock timer (Thalner Electronics, Ann Arbor, MI) that showed digital time in hundredths of a second on each video frame and marked time in l-s intervals on the polygraph and tape recorder. Video images were quantified by playing back the videotapes frame by frame on a monitor and measuring dimensions from the video screen. Distance measurements were corrected for magnification (6). Experimental

Protocols

Three sets of animal experiments were done to 1) determine resting radial pressures of the UES, 2) correlate UES pressure with cricopharyngeal and thyropharyngeal electromyographic activity during static conditions, and 3) determine the temporal and dimensional changes in UES function during swallowing as measured by manometry, videofluoroscopy, and electromyography. Radial pressure of the UES at rest. During continuous pull-throughs at 0.5 cm/s, radial pressures within the UES high-pressure zone were recorded in four directions (anterior, right, posterior, and left) using the catheter with four radial side holes. Radial peak pressures were measured in 12 dogs without electrodes and in 7 dogs with electrodes. In two dogs, recordings were made before and after electrode implantation. Recordings were obtained while the animals lay prone with their head in the same rest position. Pull-throughs were duplicated three times in each dog and the peak pressures in each radial direction were averaged. Videofluoroscopic recordings were done during continuous (0.5 cm/s) pull-throughs with the dogs on their right side to determine the spatial relationship of the anterior and posterior pressures of the UES high-pressure zone at the levels of the vocal cords and the implanted cricopharyngeus electrodes. Such recordings were obtained from six dogs without electrodes and four dogs with electrodes. Correlation of cricopharyngeal electromyography and UES pressure at rest. Using the sleeve device, oriented posteriorly, resting UES pressure was recorded simultaneously with cricopharyngeus electromyographic activity while the dogs lay quietly on their right side. To obtain a wide range of sphincter pressures, we distended the midesophagus by injecting 20-50 ml of air or excited the animal by whistling or clapping. UES function during swallowing: effect of electrodes and bolus volume. UES pressure recorded with the sleeve assembly was monitored during fluoroscopic imaging of the UES zone during swallowing in 12 animals without and in 7 animals with cricopharyngeal electrodes. Three to five spontaneous dry swallows and wet swallows of 2, 4, and 6 ml of barium (30% wt/vol) were recorded in each dog. Wet swallows were initiated by injecting meas-

UES

G913

FUNCTION

ured amounts of barium through a catheter positioned in the hypopharynx. Only swallows in which the entire bolus was transported into the esophagus in a single pharyngeal swallow were accepted for quantitative analysis. The onset, duration, and magnitude of UES opening and movement of the hyoid bone and larynx were quantified from videofluoroscopic images of the pharyngoesophageal region. UES relaxation was quantified from manometric recordings using the sleeve assembly, and cricopharyngeal relaxation was quantified from electromyographic recordings obtained from the bipolar electrodes sewn onto the cricopharyngeus muscle. Statistics Averaged values are given as means t SE. Differences among group means were tested using Tukey’s HSD multiple comparison test. Two-way analysis of variance was used to determine whether electrodes or bolus volume affected the measured variables. Relationships between variables were quantified using Pearson’s product coefficient and were tested using the regression coefficients and covariant analysis of variance (27). A P value of 0.05 or less was considered statistically significant. RESULTS

Radial and Axial

UES Pressure

With the dogs prone, the UES peak pressures in the anterior (50 -t 6 mmHg) and posterior (40 t 5 mmHg) directions were significantly higher than pressures recorded from the left (23 t 3 mmHg) or right (18 t 3 mmHg). When the animals lay on their right side, the anterior (20 -t 4 mmHg) and posterior (23 t 5 mmHg) pressures fell to the level of the pressures in the lateral directions at -20 mmHg (Fig. 2). Implantation of electrodes on the thyropharyngeus and cricopharyngeus muscles did not significantly alter these peak radial pressures (Table 1). From the pull-through tracings, axial UES pressures above atmosphere were recorded posteriorly from 2.6 cm below to 1.0 cm above the vocal cord level and anteriorly from 3.6 cm below to 1.0 cm above the vocal cords as observed on fluoroscopy. The midpoint of the peak UES

T

1 * .:

‘.:

.

12i’s

;

~

P s Anterior

Left

Posterior

PS Right

FIG. 2. Peak pressures recorded in 4 radial directions during continuous manometric pull-through across the UES. Recordings were made with dogs in a prone position (P) or on their right side (S). Numbers in bars indicate number of animals per group. * P < 0.05 for a difference in pressures between prone and side positions.

Downloaded from www.physiology.org/journal/ajpgi at Glasgow Univ Lib (130.209.006.061) on February 14, 2019.

G914

ANALYSIS OF UES FUNCTION

TABLE 1. Comparison

of peak radial effects

UES pressures

recorded in prone position: of pharyngeal electrodes

Peak Radial Pressure, mmHg

Animal

Group

Anterior

TP-EMG

200/A/ [

CP-EMG

2OOpV [

J’(F) Left Posterior Right Direction E/NE

No electrodes (n = 12) 50+6 23+3 4025 189~2 0.05). Anterior

Posterior

UES Pressure (mm Hg)

$ o E-

30Electrod

-No

-Aborad

t--l--l-

0

50

Pressure

25-

--~Electrodes 100

100

50

0

g

20-

5

15-

z e

lo-

(% of Maximal)

FIG. 3. Axial pressure profile across pharyngoesophageal junction relative to the position of implanted cricopharyngeal electrodes and relative to vocal cords. Anterior and posterior peak UES pressures corresponded closely with mean axial position of cricopharyngeal electrodes. Shaded area around mean electrode position line depicts SE. Implantation of electrodes on the cricopharyngeus and thyropharyngeus had negligible effect on axial pressure profile of the UES.

pressure zone (~70% of maximal pressure) was 1.2 and 1.1 cm below the vocal cords in the anterior and posterior directions, respectively. Implantation of electrodes on the thyropharyngeus and cricopharyngeus did not significantly alter this axial pressure profile. The midpoint of the peak UES high-pressure zone was close to the location of the implanted cricopharyngeal electrodes at 1.5 + 0.1 cm (n = 7) below the vocal cords. This position corresponded to a zone where the pressure was 55 and 72% of maximum in the posterior and anterior planes, respectively (Fig. 3). The video frame in Fig. 1 is an example of the results of this experiment. This video frame corresponded to the time at which peak axial pressure was recorded in the posterior plane. At this time, the axial position of the manometric recording orifices (located just orad to the parallel marker bars) corresponded closely with the level of the implanted cricopharyngeal electromyographic electrodes. Correlation of Cricopharyngeal With Basal Pressure

Electromyography

Electromyographic activity of the cricopharyngeus, but not the thyropharyngeus, closely reflected the UES pressure when the dog lay on its side without swallowing (Fig. 4A). When the integrated electromyographic activity of the cricopharyngeus and thyropharyngeus was

0

lb

i0

i0

4b

5b

$0

i’0

d0

60

160

UES Pressure (mm Hg) FIG. 4. Relationship of electrical activity of cricopharyngeus (CP) and thyropharyngeus (TP) muscles to UES pressure during resting conditions. A: representative chart recordings of cricopharyngeal and thyropharyngeal electromyographic (EMG) activity and UES pressure recorded simultaneously. Note the close correspondence of cricopharyngeal EMG activity, integrated cricopharyngeal EMG activity (JCPEMG), and UES pressure. B: plot of randomly selected UES pressures with corresponding integrated EMG activity of the cricopharyngeus (JCP-EMG)and thyropharyngeus (JTP-EMG). In this animal, slope of regression lines of UES pressure vs. integrated cricopharyngeal electromyography, but not integrated thyropharyngeal electromyography, was significantly (P < 0.05) different from zero. Comparable results were obtained in each of the 6 animals studied.

plotted against the UES pressure at randomly selected points in time, only integrated cricopharyngeal electromyographic activity correlated significantly (r = 0.87 of: 0.02; P < 0.01) with UES pressure in each animal (Fig. 4B and Table 2). Also, analysis of covariance indicated that integrated cricopharyngeal, but not thyropharyngeal, electromyographic activity significantly contributed to the basal UES pressure (Table 2). Manometric, Videofluoroscopic, and Electromyographic Assessment of UES Function during Swallowing Temporal relationships of UES function during swallowing, as measured by manometry, videofluoroscopy,

Downloaded from www.physiology.org/journal/ajpgi at Glasgow Univ Lib (130.209.006.061) on February 14, 2019.

ANALYSIS

OF

2. Comparison of relationships between basal UES pressure and integrated cricopharyngeal and thyropharyngeal electromyography TABLE

Muscle

scp f TP

Regression

Correlation (4

Coefficients I’(F)

Slope

0.87-iO.OtL” 0.28tO. 11

Intercept

0.44tO.07* 0.0~t0.01

1.4MO.87 0.71it0.26

co.01 NS

Values are means k SE for 6 animals. Y(F), probability that the cricopharyngeal (CP) or thyropharyngeal (TP) electrical activit,y contributed to UES pressure based on covariate ANOVA; NS, no significant contribution (P > 0.05); * 1’ c 0.01 for a difference between CP and TP EMG using St,udent’s t test. TP-EMG

*-

CP-EMG

6%

FIG. 5. Simultaneous recording of cricopharyngeal (CP) and thyropharyngeal (TP) EMG activity, manometric pressure within the I!ES, and flow across the UES during a 4-ml barium bolus swallow. IJESP, upper esophageal sphincter pressure. Hatched horizontal bar indicates duration of barium flow across sphincter. Note temporal relationships among cricopharyngeal relaxation, i.e., cessation of cricopharyngeal EMG activity; manometric UES relaxation, i.e., period of’decreased pressure within UES high-pressure zone; and UES opening time, i.e., duration of barium flow across the UES.

Start

I

-.lO

0

Time(s)

End

I

I

I

.lO

.20

.30

Relative

to Hyoid

.40

50

Movement

FIG. 6. Temporal relationships among EMG cricopharyngeal (CP) relaxation, manometric LJES relaxation, and LJES opening during swallowing @-ml bolus) relat,ive to onset of hyoid movement. Start and end of hyoid movement are indicated by vertical lines (shaded areas depict SE). Horizontal bars depict mean t SE onset and offset of measured variable relative to start of hyoid movement. Clear bars and solid lines depict data from noninstrument,ed dogs (n = 8), and hatched bars and dotted lines depict data from instrumentled (n = 6) dogs. Note that electrode implantation significantly delayed time of UES closure (“I’ < 0.05 using Student’s t t,est).

and cricopharyngeal electromyographic activity, are illustrated in Fig. 5. The swallow was initiated by a 4-ml barium bolus. The initial event during the swallow was relaxation of the cricopharyngeus muscle on electromyography, which was followed by manometric relaxation of the UES and then opening of the sphincter. Sphincter closure began when the pharyngeal peristaltic contraction reached the UES and cricopharyngeal electromyographic activity reappeared. To quantify these temporal relationships and determine the effects of the electrodes on this response, the timing of these events was referenced to the beginning of hyoid movement (Fig. 6). We found that the relaxation of the cricopharyngeus began just before the onset of hyoid movement, -100 ms

UES

G915

FUNCTION

before the beginning of manometric relaxation of the UES and -200 ms before the UES opened. Manometric relaxation of the UES or UES opening was not altered by implantation of the electrodes. Although electromyographic relaxation of the cricopharyngeus occurred significantly earlier than manometric relaxation of the UES or UES opening, the end of electromyographic relaxation of the cricopharyngeus coincided with the end of manometric relaxation. Closure of the UES also occurred coincident with the end of manometric relaxation when electrodes were not on the thyropharyngeus and cricopharyngeus. The implantation of these electrodes, however, lengthened the opening time of the sphincter by -0.1 s. Studies in humans (6) and in oppossums (3) suggested that anterior retraction forces may contribute to manometric relaxation of the UES or UES opening; therefore, we further quantified the video images to correlate movement of the larynx and hyoid relative to cricopharyngeal relaxation (Fig. 7). We found that superior movement onset of the larynx or hyoid was closely related to manometric UES relaxation and that onset of anterior movement of the larynx or hyoid was closely related to the onset of UES opening. To determine whether onset of hyoid or laryngeal movement preceded and therefore perhaps caused either manometric relaxation of the UES or UES opening, histograms of these temporal differences during individual swallows were constructed. Analyses revealed 1) onset of superior laryngeal or hyoid movement did not occur consistently before or after manometric UES relaxation (Fig. 8), 2) onset of hyoid or laryngeal superior movement always preceded UES opening with a median interval of 0.1 s (Fig. 9), and 3) anterior movement of the larynx, but not the hyoid, almost always preceded UES opening, and the median interval of anterior laryngeal movement was 67 ms (Fig. 8). For the 4 of 164 swallows in which anterior laryngeal movement followed UES opening, this interval was one video frame. Bolus size or the implantation of thyropharyngeal and cricopharyngeal electrodes did not affect any of the temporal measures of UES function except closure of UES. The presence of electrodes on the cricopharyngeus sigEvd

Start

)%g%iJ&

~zg%jip

I .I0

0 Time

I I I I I .30 .40 .50 .60 .20 (s) Relative to CP Relaxation

FIG. 7. Temporal relationships of anterior and superior laryngeal hyoid movement, LJES opening, and manometric UES relaxation relative to start and end of EMG cricopharyngeal (CP) relaxation. Note that onsets of’ superior laryngeal and hyoid movement correspond closely with onset of manometric UES relaxation, whereas onsets of anterior movement, of t,he larynx and hyoid correspond closely with UES opening.

Downloaded from www.physiology.org/journal/ajpgi at Glasgow Univ Lib (130.209.006.061) on February 14, 2019.

G916

ANALYSIS 24 20

OF

FUNCTION

3. Effect of bolus volume and pharyngeal electrodes on temporal measurements of UES function during swallowing TABLE

Superior Hyoid Movement

16 12 m834-

UES

“7

2 0

2 5 24 z 20

2 4

Superior

6

2

CP EMG Offset Onset Duration UES pressure Offset

Laryngeal

Onset

n 6

4

2

0 2 4 6 81012

Before

Duration

After

Time (Video of Onset Relative

Frame,’ 1/3Os) to UES Relaxation

FIG. 8. Relationships of onset of superior hyoid (top) and superior laryngeal (bottom) movement relative to the beginning of manometric UES relaxation during swallowing. Time is shown as number of video frames (l/30 s each). Note similar distributions of onset time of superior movements for hyoid and larynx relative to that of UES relaxation. Onsets of superior hyoid and superior laryngeal movement do not occur preferentially either before or after beginning of manometric UES relaxation.

Volume,

ml

P(F)

Group

81012

16 12 8 4

”

Bolus

UES Function

m

UES patency Open Closed Duration

E E E

4

E/NE

6

Volume

-0.12kO.02 -0.08kO.01 -0.08kO.01 0.28kO.02 0.31t0.02 0.31kO.02 0.40t0.02 0.39t0.02 0.3720.02

NS NS NS

E NE E NE E NE

0.02~0.02 0.00~0.04 0.30t0.01 0.26t0.04 0.31t0.03 0.25kO.06

0.00~0.03 0.01~0.04 0.33t0.02 0.29kO.05 0.33t0.02 0.28t0.05

O.OOt0.02 NS 0.06kO.01 0.32t0.02 NS 0.32kO.06 0.32kO.02 NS 0.26kO.08

NS

E NE E NE E NE

0.11t0.02 0.14~0.01 0.41t0.03 0.34kO.02 0.29kO.03 0.19t0.02

O.lltO.O1 0.12*0.01 0.44kO.04 0.32t0.01 0.32t0.02 0.20~0.01

O.lOt0.01

NS

NS NS

NS

0.11~0.01 0.45&0.06O.l5 s. These relatively long delays cannot be attributed to the delay between muscle activation and relaxation, because such delays of slow twitch muscles like the cricopharyngeus are ~0.05 s (4). The relatively long delays between cricopharyngeal electro-

Downloaded from www.physiology.org/journal/ajpgi at Glasgow Univ Lib (130.209.006.061) on February 14, 2019.

G918

ANALYSIS

OF LJES FIJNCTION

myographic and manometric UES relaxation may have been due to pressure generated from some other source, e.g., the thyropharyngeus, or may indicate that the entire cricopharyngeus muscle may not relax simultaneously. Some investigators have assumed that manometric UES relaxation occurs simultaneously with cricopharyngeal relaxation (3, 6), but this may not be true. In the only other study in which cricopharyngeal electromyographic activity was recorded concurrent with UES pressure during swallowing (29), this relationship was not quantified. Although we did not record directly from the suprahyoid muscles, we monitored the effects of h.yoid muscle activity by recording movement of the hyoid bone and larynx using videofluoroscopy (6). Superior movement of the hyoid and larynx occurred in close temporal association with UES relaxation, while’the anterior movement nearly always occurred just before UES opening. These findings are consistent with results obtained in humans (6). Further temporal analysis revealed that even though the mean onset of superior hyoid or laryngeal movement preceded UES relaxation onset, no consistent temporal relationship existed in this regard. Therefore, although on average the superior movement of the hyoid and larynx occurred concomitantly with UES relaxation, the superior movement of these structures probably did not cause UES relaxation. Movement of the hyoid and larynx, however, may have a function in UES opening. Superior movement of the hyoid and larynx occurred before UES opening during every swallow, but the average difference was -0.1 s before sphincter opening. Superior movement of these structures probably did not cause UES opening directly but may have been a prerequisite for normal opening of the sphincter. On the other hand, the average onset of anterior laryngeal movement occurred immediately before UES opening and averaged 0.03 s. During all but four swallows (160 of 164), the larynx moved anteriorly concurrent with or just before the UES opened. In each of these four swallows, the anterior laryngeal movement occurred one video frame after UES opening. The inherent recording system error was t 1 video frame (i.e., to.03 s); therefore, these four measurements may not reflect physiological function. The results, therefore, are consistent with data obtained from humans (6,14) and suggest that anterior movement of the larynx may initiate UES opening by traction (6, 14). UES opening is also controlled by cricopharyngeal relaxation, UES compliance, and intrabolus pressure (6, l4), and these factors may have accounted for the remainder of the variation in delay between anterior laryngeal movement and UES opening. The average onset of anterior hyoid movement also corresponded closely to the onset of UES opening, but during many swallows the sphincter opened before the hyoid moved anteriorly. Therefore, anterior hyoid movement does not appear to contribute directly to UES opening in dogs. The fact that anterior laryngeal movement, but not anterior hyoid movement, nearly always occurred just before or concurrent with UES opening suggeststhat the thyrohyoideus contributes significantly to opening of the UES in dogs. The temporal relationship of hyoid and laryngeal movement to UES relaxation and

opening in dogs is similar and consistent with recent findings in human subjects (6, 14). Studies of UES function in humans using concurrent manometry and videofluoroscopy have shown that some measures of UES function depend on bolus volume, i.e., UES relaxation duration, UES opening time, and superior and anterior movement of the larynx and hyoid (6, 14, 17). Onset time of these events occurred earlier in the swallow sequence as bolus volume was increased (6). Such relationships were not found in dogs, although increasing bolus volume did increase sagittal UES diameter. Three possible explanations for these differences between the findings of human studies and the dog studies are 1) the bolus volumes we used in dogs were too small to cause changes in UES function, 2) the difference in oral swallowing mechanisms between dogs and humans may indirectly affect measures of the pharyngeal swallowing mechanisms, or 3) the mechanisms by which UES function responds to bolus size do not exist in dogs. In the human studies, bolus volumes up to 30 ml were used, but many measures showed very little change up to a 5-ml bolus (6, 14, 17). In our studies, we were not able to get the dogs to consistently swallow >6 ml in a single bolus. Although increasing volume significantly increased sagittal diameter of the canine UES, we may not have stressed the swallowing mechanisms sufficiently to elicit the same temporal changes as those observed in humans. The oral phase in swallowing differs between animals and humans. Humans form a bolus with their tongue and swallow it in a single coordinated motion from tongue to esophagus. In contrast, dogs and cats use their tongue to repetitively pump small amounts of food into the pharynx, where it collects until a pharyngeal phase of swallowing is initiated and the oropharyngeal bolus is transported into the esophagus. It is possible that the voluntary adjustments to bolus size during the oral phase of swallowing in humans may indirectly alter the function of the UES by altering the action of the hyoid muscles in preparation for the pharyngeal phase of swallowing. Nevertheless, the most direct method of recording muscle function during swallowing is by electromyographic activity. The fact that we did not observe a relationship between bolus size and cricopharyngeal activity suggests that the central mechanisms controlling canine cricopharyngeal function during swallowing were not altered by reflex mechanisms. Although some videofluoroscopic and manometric measures of UES function change with bolus volume in humans (6, 14, 17), it is not known which muscles are responsible for these changes. Until cricopharyngeal electromyographic activity is recorded during swallowing in humans, the effect of varying bolus volume on human cricopharyngeal function and the mechanisms by which UES function responds to bolus size will remain unknown. The presence of electrodes on the thyropharyngeus and cricopharyngeus had little effect on the manometric and videofluoroscopic measures of UES function at rest or during swallowing. Only two electrode effects were observed: 1) prolongation of UES opening during bolus swallows and 2) restriction of the maximal superior movement of the hyoid or larynx. Both effects were

Downloaded from www.physiology.org/journal/ajpgi at Glasgow Univ Lib (130.209.006.061) on February 14, 2019.

ANALYSIS

OF

probably because of mechanical factors. We speculate that the Silastic backing of the electrodes may have prevented normal UES closure when a manometric catheter was placed in the lumen, and thereby allowed the sphincter to remain open longer than normal during a bolus swallow. In addition, adhesions resulting from surgical implantation of the electrodes on the muscles may have restricted superior deglutitive movement of the hyoid and larynx. We conclude that 1) the cricopharyngeus muscle is the primary pharyngeal constrictor responsible for basal pressure of the canine UES, 2) basal tone of the UES and cricopharyngeus is continuous but not constant, 3) cricopharyngeal relaxation is a prerequisite for UES opening and occurs -0.2 s before sphincter opening, 4) traction by anterior laryngeal movement is probably the main force that initiates UES opening during swallowing, and 5) the central swallowing program that controls the canine cricopharyngeus is not reflexly altered by changes in bolus volume. The secretarial assistance of Jan Staedler was greatly appreciated. This project was supported by National Institutes of Health Grant ROl-DC-00669-01 (W. J. Dodds) and VA Merit Review Grant 512002P (I. M. Lang). Address for reprint requests: I. M. Lang, Surgical Research 151, Zablocki VA Medical Ctr., Milwaukee, WI 53295. Received

20 August

1990; accepted

in final

form

26 January

1991.

REFERENCES

UES

11.

12.

13.

14.

15.

16.

17.

18.

19. 20.

21.

1. ANDREW, B. L. The nervous control of the cervical oesophagus of the rat during swallowing. J. Physiol. Lond. 134: 729-740, 1956. 2. ARNDORFER, R. C., J. J. STEF, W. ?J. Dorms, J. H. LINEHAN, AND W. J. HOGAN. Improved infusion system for intraluminal esophageal manometry. Gastroenterology 73: 23-27, 1977. 3. ASOH, R., AND R. K. GOYAL. Manometry and electromyography of the upper esophageal sphincter in the opossum. Gastroenterology 74: 514-520, 1978. 4. BASMAJIAN, J. V., AND C. J. DELUCA. Muscles Alive: Their Functions Revealed by Electromyography (5th ed.). Baltimore, MD: Williams & Wilkins, 1985. 5. CAR, A., AND C. ROMAN. L’activite spontanee du sphincters oesophagien superieur chez le mouton. J. Physiol Paris 62: 505511,197o. 6. COOK, I. ,J., W. ,J. DODDS, R. 0. DANTAS, B. MASSEY, M. K. KERN, I. M. LANC;, J. G. BRASSEUR, AND W. ?J. HOGAN. Opening mechanisms of the human upper esophageal sphincter. Am. J. Physiol. 257 (Gastrointest. Liver Physiol. 20): G748-G759, 1989. 7. DOTY, R. W. Neural organization of deglutition. In: Handbook of Physiology. Alimentary Canal. Motility. Washington, DC: Am. Physiol. Sot., 1968, sect. 6, vol. IV, p. 1861-1902. 8. DOTY, R. W., ANI) ,J. F. BOSMA. An electromyographic analysis of reflex deglutition. J. Neurophysiol. 19: 44-60, 1956. 9. EKRERC;, O., ANI) C. L~JNDSTR~M. The upper esophageal sphincter area. Acta Radiol. 28: 173-176, 1987. 10. GERHARDT, D., J. HEWETT, M. MOESCHRERGER, T. SCHUCK, AND

22. 23. 24.

25.

26.

27. 28. 29.

30.

FUNCTION

G919

D. WINSHIP. Human upper esophageal sphincter pressure profile. Am. J. Physiol. 239 (Gastrointest. Liver Physiol. 2): G49-G52, 1980. HELLEMANS, ,T., G. VANTRAPPEN, AND J. JANSSEN. Electromyography of the esophagus. In: Diseases of the Esophagus, edited by G. Vantrappen and ?J. Hellemans. New York: Springer-Verlag, 1974, p. 270-285. ISBERG, A., M. E. NILSON, AND H. SCHIRATZKI. The upper esophageal sphincter during normal deglutition. Acta Radiol. Diag. 26: 563-568, 1985. JACOB, P., P. ,J. KAHRILAS, G. HERZON, T. HA, AND B. McLAUGHLIN. Upper esophageal sphincter tone is augmented by a manometric device and diminished by anesthesia in the dog (Abstract). Clin. Res. 37: 936A, 1989. JACOB, P., P. J. KAHRILAS, J. A. LOGEMANN, V. SHAH, AND T. HA. Upper esophageal sphincter opening and modulation during swallowing. Gastroenterology 97: 1469-1478, 1989. KAHRILAS, P. J., W. (J. DODDS, J. DENT, B. HAEBERLE, W. J. HOGAN, AND R. C. ARNDORFER. Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers. Gastroenterology 92: 466471, 1987. KAHRILAS, P. J., W. J. DODDS, J. DENT, W. J. HOGAN, AND R. C. ARNDORFER. A method for continuous monitoring of upper esophageal sphincter pressure. Dig. Dis. Sci. 32: 121-128, 1987. KAHRILAS, P. ?J., W. J. DODDS, J. DENT, J. A. LOGEMANN, AND R. SHAKER. Upper esophageal sphincter function during deglutition. Gastroenterology 95: 52-62, 1988. KAWASAKI, M., J. H. OGURA, AND S. TAKENOUCHI. Neurophysiologic observations of normal deglutition. II. Its relationship to allied phenomena. Laryngoscope 74: 1766-1780, 1964. KIRCHNER, J. A. The motor activity of the cricopharyngeus muscle. Laryngoscope 68: 1119- 1159, 1958. LANG, I. M., J. MARVIN;, ANI) S. K. SARNA. Electromyography (EMG) of the pharyngoesophageal junction (PEJ) during various physiologic states (Abstract). Gastroenterology 94: A249, 1988. LEVITT, M. N., H. H. DEDO, AND J. H. OGURA. The cricopharyngeus muscle, an electromyographic study in the dog. Laryngoscope 75: 122-136, 1965. LUND, W. S. The function of the cricopharyngeal sphincter during swallowing. Acta Otolaryngol. 59: 497-510, 1965. MILI,ER, A. ,J. Deglutition. Physiol. Rev. 62: 129-184, 1982. MURAKAMI, Y., H. FUKUDA, ANI) J. A. KIRCHNER. The cricopharyngeus muscle. An electrophysiological and neuropharmacological study. Acta Otolaryngol., Suppl. 311: l-19, 1972. REYNOLDS, R. P., G. W. EFFER, AND M. P. BENDECK. The upper esophageal sphincter in the cat: the role of central innervation assessed by transient vagal blockade. Can. J. Ph-ysiol. Pharmacol. 65: 96-99, 1987. %IPP, T., W. W. DEATSCH, AND K. ROBERTSON. Pharyngoesophageal muscle activity during swallowing in man. Laryngoscope 80: 1-16, 1970. SNEDECOR, G. W., AND W. G. COCHRAN. Statistical Methods (6th ed.). Ames: Iowa State Univ. Press, 1967. TANAKA, E., J. PALMER, AND A. SIEBENS. Bipolar suction electrodes for pharyngeal electromyography. Dysphagia 1: 39-40, 1986. VAN OVERBEEK, J. J., H. P. WIT, R. H. PAPING, AND H. M. SEGENHOUT. Simultaneous manometry and electromyography in the pharyngoesophageal segment. Laryngoscope 95: 582-584, 1985. WELCH, R. W., K. LUCKMANN, P. M. RICKS, S. T. DRAKE, AND G. A. GATES. Manometry of the normal upper esophageal sphincter and its alterations in laryngectomy. J. Clin. Invest. 63: 1036-1041, 1979.

Downloaded from www.physiology.org/journal/ajpgi at Glasgow Univ Lib (130.209.006.061) on February 14, 2019.