Vol. 282, Issue 5, G785-G793, May 2002
A novel ultrasound technique to study the biomechanics of the
human esophagus in vivo
Torahiko
Takeda1,
Ghassan
Kassab2,
Jianmin
Liu1,
James L.
Puckett1,
Rishi R.
Mittal1, and
Ravinder K.
Mittal1
1 Division of Gastroenterology, Veterans Affairs
Medical Center, University of California, San Diego, 92161; and
2 Center for Biomedical Engineering, University of
California, Irvine, California 92697
 |
ABSTRACT |
The objectives of
this study were to validate a novel ultrasound technique and to use it
to study the circumferential stress-strain properties of the human
esophagus in vivo. A manometric catheter equipped with a
high-compliance bag and a high-frequency intraluminal ultrasonography
probe was used to record esophageal pressure and images. Validation
studies were performed in vitro followed by in vivo studies in healthy
human subjects. Esophageal distensions were performed with either an
isovolumic (5-20 ml of water) or with an isobaric (10-60
mmHg) technique. Sustained distension was also performed for 3 min in
each subject. The circumferential wall stress and strain were
calculated. In vitro studies indicate that the ultrasound technique can
make measurements of the esophageal wall with an accuracy of 0.01 mm.
The in vivo studies provide the necessary data to compute the
Kirchhoff's stress, Green's strain, and Young's elastic modulus
during esophageal distensions. The stress-strain relationship revealed
a linear shape, the slope of which corresponds to the Young's modulus.
During sustained distensions, we found dynamic changes of stress and
strain during the period of distension. We describe and validate a
novel ultrasound technique that allows measurement of biomechanical
properties of the esophagus in vivo in humans.
Kirchhoff's stress; Green's strain; Young's modulus
| |
INTRODUCTION |
THE BIOMECHANICAL
PROPERTIES of the wall of the esophagus are an important
determinant of the motor and sensory function of the esophagus. Both
active (muscle contractions) and passive (elastic and visco-elastic
properties) properties of the esophageal wall contribute to these
biomechanical properties. The biomechanical properties of a tissue are
expressed through its stress-strain relationship. A number of
investigators have attempted to determine the circumferential
tension-strain or stress-strain relationship of the esophagus by using
various in vivo and in vitro techniques (1, 2, 4, 5, 8).
To determine such a relationship, one must measure both the loading
(pressure) and the deformation [changes in cross-sectional area (CSA)
and wall thickness] simultaneously. To date, there has been no method
to measure these parameters simultaneously in the human esophagus in
the in vivo state. Gregersen et al. (5) developed the
technique of impedance planimetry for measurement of pressure and CSA
of the gastrointestinal tract. Their technique, however, does not
measure the wall thickness and therefore allows computation of wall
tension (pressure × radius) but not wall stress (pressure × radius/wall thickness). Jorgensen et al. (8) combined the
impedance planimetry method with A-mode ultrasound to measure the wall
thickness during distension. However, wall thickness was measured in
only one direction and CSA was calculated indirectly on the basis of
the impedance of the saline solution inside the balloon.
The purpose of the present study is to introduce a rather simple, novel
technique that combines manometry with B-mode ultrasonography to
measure pressure, radius, and wall thickness of the esophagus directly,
simultaneously, and continuously. This novel technique allows
calculations of the circumferential stress, strain, and elastic modulus
on a continuous-time basis. We performed in vitro studies to validate
the accuracy of the technique and then studied the stress-strain
relationship of the esophageal wall in healthy normal subjects.
| |
MATERIALS AND METHODS |
In vitro studies.
An in vitro validation study was performed using a 20-MHz,
high-frequency intraluminal ultrasonography (HFIUS) probe (UM-3R; Olympus, Tokyo, Japan) positioned in water in the agar tubes. Three
tubes of different wall thickness and lumen size were constructed from
3% agarose. Measurements of the wall thickness and inner radius were
made using a caliper and the ultrasonographic method to determine the
accuracy of the latter technique. A slide caliper with an accuracy of
0.01 mm was used. The mean wall thickness and inner radius were
measured at four quadrants along the circumference of the tube in
ultrasonographic measurement. The measurements were made in three
different configurations, with the probe positioned in the center of
the tube, off center, and center of the tube with a 15° angle between
the transducer and the wall of the tube. A composite tube with an inner
layer of 1% agarose and an outer layer of 3% agarose was also
constructed to simulate a multilayered esophagus. For these
measurements, the HFIUS probe was placed vertically in the center of
the tube.
In vivo studies.
The study was performed in 18 healthy volunteers, 13 men and 5 women.
The age of the volunteers ranged from 18 to 62 years (median 32.7 years). Volunteers with a history of upper gastrointestinal surgery or
systemic diseases known to influence gastrointestinal motility and
volunteers that were taking medications that can affect the esophagus
were excluded from the study. The study was approved by The Human
Subjects Committee of the University of California, San Diego.
Measurement system.
An esophageal catheter assembly consisting of a 6.2-Fr catheter
equipped with a HFIUS probe, a manometry catheter, and a
high-compliance polyvinyl bag was used for the in vivo studies, as
shown in Fig. 1.
View larger version (20K):
[in this window]
[in a new window]
|
Fig. 1.
A schematic diagram of the catheter assembly. Note that
soft vinyl support is used to place the high-frequency intraluminal
ultrasonography probe at the central axis of the bag.
|
|
The length and maximum diameter of the bag were 5 cm and 3.5 cm,
respectively. The distensibility of the bag was measured in
vitro, before its use in each subject, to determine the
range of bag volume used for in vivo studies. We were able to inflate this 0.03-mm-thick bag to a volume of 25 ml without stretching the bag
wall. This maximal volume was never exceeded in the in vivo studies,
which ensures that the elastic properties of the bag itself do not
contribute to the intrabag pressure in the in vivo situation. The
ultrasound probe catheter was anchored at the proximal and distal ends
of the bag, which ensured that the ultrasound transducer stayed in the
center of the bag.
The manometric catheter assembly had four side holes, with openings
located inside the bag and at 2, 7, and 12 cm proximal to the bag. The
2, 7, and 12 cm holes were perfused with distilled water at a rate of
0.5 ml/min using a low-compliance pneumohydraulic perfusion system
(Arndorfer Medical Specialties, Greendale, WI). The pressure recordings
from the four ports of the manometric catheter were input into a
personal computer via a polygraph (Medtronic Synectics Medical,
Stockholm, Sweden). The ultrasound and manometric recordings were
synchronized using a video timer.
Study protocol.
After a >5-h fast, the volunteer's throat was sprayed with lidocaine
HCl (Xylocaine Astra, Westborough, MA). With the subject sitting in the
upright position, the lubricated assembly was passed transnasally or
transorally until the tip was 60 cm from the nostril or 55 cm from the
incisors. The subject was then placed in the semirecumbent position.
After an adjustment period of 5-10 min, the assembly was pulled
back in 1-cm steps while the manometric pressure recordings were
observed on the computer monitor. The lower esophageal sphincter (LES)
was identified as a high-pressure zone that relaxed in response to a
swallow, and its location was noted in relation to the nostril or
incisors. The center of the bag was then positioned at 7.5 cm above the
LES, and the catheter assembly was anchored at the nostril or at the
angle of the mouth with adhesive tape.
After a rest period of 10 min, the bag was inflated with various
volumes of water for at least 20 s by injecting water into the bag
via a manually held syringe (isovolumic study). The rate of injection
was ~2 ml/min. This constituted the short-period distension study.
The infused volume was set at 7.5, 12.5, 5, 10, 15, 20, and 17.5 ml, in
that order. The steady point was defined as the time at which intrabag
pressure had been constant and the lowest. Each distension was followed
by a 30-s rest period. Each volume was tested three times. After this
short-period distension protocol, 15 ml distension for 3 min was also
performed and repeated two times in each subject. This constituted the
sustained esophageal distension study. Esophageal distensions were also
performed by using a constant-pressure technique (isobaric study). The
bag was distended with water at 20, 40, 60, 10, 30, and 50 mmHg, in that order, via a water reservoir (sterile water bag) placed at the
appropriate vertical height. It took ~20-30 s to reach the maximum distension, and the distension was sustained for another 20 s. The steady-state point was defined as that at which the CSA
of the lumen reached a maximum. Each distension was followed by a 30-s
rest period. Each pressure was tested two times. After this
short-period distension protocol, 40 mmHg distension was performed for
3 min and repeated two times in each subject. Ten subjects participated
in the isovolumic study and 8 subjects in the isobaric study. During
bag distension, the subjects were asked to keep still, to make no
attempt to speak, and to refrain from swallowing. To determine the
esophageal dimensions of a relaxed esophagus, we injected atropine (15 µg/kg) through an antecubital vein. An image of the esophagus was
captured, at zero bag pressure, ~10 min after the injection.
Data measurements.
The ultrasound images were recorded in real time using a
high-resolution ultrasound unit and a videotape recorder (Sony, Tokyo, Japan). The ultrasound images were digitized on a personal computer equipped with a high-definition video card (Targa+; Truevision, Indianapolis, IN) and analyzed by using a commercially available image
analysis software package (Mocha; Jandel Scientific, San Rafael, CA).
Images were displayed on a 17-inch high-resolution monitor with pixel
size of 640 × 480. This corresponds to an image magnification of
approximately ×12 (10 pixels = 1 mm). The ultrasound image was
captured at a steady state point as mentioned previously. The intrabag
pressure was also measured at the same time. The perimeters of the bag
and outer esophageal wall were traced for each image by using a
computer program. The former corresponds to the inner circumference,
and the latter corresponds to the outer circumference of the esophageal
wall. Once outlined, the software program automatically calculated the
luminal CSA and circumferential length of the esophagus
(l
). The wall thickness of the esophagus was
measured at four different quadrants around the esophagus, and a mean
wall thickness (h) was calculated (Fig. 2). The circular radius of the lumen of
the esophagus (r) was calculated as r = (CSA/
)1/2.
View larger version (56K):
[in this window]
[in a new window]
|
Fig. 2.
A: ultrasound (US) image at 15 ml distension.
B: schematic of the measurement of luminal cross-sectional
area (CSA), the circumferential length of the esophagus
(l), and mean wall thickness (average over
the length of the four arrows).
|
|
Biomechanical analysis.
The circumferential deformation of the esophagus may be described by
the Green's strain (
), which is defined as follows
|
(1)
|
where 
is the circumferential stretch ratio
given by =
l/L, where
l is the circumferential length of the
esophagus at a given distension and L is the circumferential length at zero pressure after the injection of atropine
(15 µg/kg iv). Because the outer muscle wall was the most prominent
and easily recognized on the ultrasound images, the outer wall strain
was computed during distensions.
At an equilibrium condition, the average circumferential Kirchhoff's
stress in the esophageal wall at a given distension can be computed
according to the following equation, with an assumption that the shape
of the esophagus is cylindrical
|
(2)
|
where P is the luminal pressure and r and
h are the radius and wall thickness of the esophagus,
respectively. Ideally, one should relate the mean stress to the midwall
strain. However, because the data on the outer circumference is more
accurate, we calculated the mean stress and strain at the outer wall.
Hence, the depicted data correspond to the biomechanical properties of the outer layer of the esophagus.
Statistical analysis.
Some of the data were normally distributed and others were not;
therefore, we used the Mann-Whitney rank-sum test for statistical comparisons. The results are shown as means ± SE.
| |
RESULTS |
In vitro studies.
There was excellent agreement between the measurements made by the
calipers and the ones made by analysis of the ultrasound images. The
most accurate measurements of radius of the tube and wall thickness
were made when the HFIUS probe and the transducer were located in the
center and parallel to the wall of the tube. When the transducer was
located at an off-center position or at an angle, the entire
circumference of the tube was not well visualized. However,
measurements at four quadrants could be performed from the portions of
the tube that were visualized adequately even during such off-center
and angled positions, and it showed that the error was <4.0%. The
composite tube was also well visualized with a measurement accuracy of
>98% (Table 1).
In vivo studies.
One subject completed the preatropine portion of the isovolumic study
but refused the injection of atropine. Nine subjects completed the
entire isovolumic study, and eight subjects completed the entire
isobaric study (before and after atropine). One subject felt severe
chest pain at 17.5 and 20 ml distension, so second and third
distensions were not performed. Because of difficulty in refraining
from swallowing for long period, some sustained esophageal distensions
were not performed adequately. Nine subjects in the isovolumic study
and six subjects in the isobaric study completed the sustained
esophageal distension study at least one time. The sustained esophageal
distension with the longest swallow-holding period was analyzed for
each of these subjects. The image quality was excellent with adequate
visualization. The border between the bag lumen and esophageal
wall was clear during distensions. The lining of the bag and mucosa
could not be distinguished from each other in the ultrasound images.
However, esophageal muscle wall could still be seen as a hypoechoic
band, so the outer border of the esophagus could be outlined
successfully even during deflation. The relationships between
intrabag pressure, bag volume, and esophageal luminal CSA are
shown in Fig. 3. Both relationships
exhibit a linear tendency.
View larger version (18K):
[in this window]
[in a new window]
|
Fig. 3.
Relationship between intrabag pressure (P) and bag volume
(V) ( ) and between luminal CSA and bag volume
( ) (n = 10). The data are fitted by a
linear least-squares fit. P = 2.36V + 22.9 (r2 = 0.98) and CSA = 30.9V  48.0 (r2 = 0.99).
|
|
Figure 4 shows that a linear relationship
also exists between the esophageal luminal CSA and bag pressure during
isovolumic and isobaric distensions. The esophageal compliance in the
circumferential direction, determined from the slope of the
CSA-pressure relationship, tended to be higher for isovolumic
distensions compared with isobaric distensions (P = 0.066; 8.18 ± 1.17 and 4.97 ± 0.97 mm2/mmHg in
isovolumic and isobaric studies, respectively). It should be noted that
during isovolumic distensions of 17.5 and 20 ml, the generated pressure
exceeded 60 mmHg.
View larger version (19K):
[in this window]
[in a new window]
|
Fig. 4.
Luminal CSA-pressure relationships in isovolumic
(; n = 10) and isobaric
(; n = 8) distension studies. The
linear least-squares fit of the average data for the isovolumic and
isobaric distensions are CSA = 12.6P 322 (r2 = 0.938) and CSA = 4.68P + 92.7 (r2 = 0.996), respectively.
|
|
Effect of atropine.
After administration of atropine, swallow-induced contraction amplitude
was decreased by 72%, as determined from the pressure at 2 cm above
the bag (82.9 ± 7.5 vs. 22.0 ± 2.2 mmHg). Also, L increased significantly, from 43.5 ± 1.5 to 49.8 ± 2.3 mm (P = 0.021), after atropine injection.
Circumferential stress-strain relationship during distension.
In the isovolumic study, there was a linear increase in the strain,
which ranged from 0.26 ± 0.09 to 1.77 ± 0.24 and a
linear increase in the stress, which ranged from 7.54 ± 0.70 to
15.28 ± 1.97 kPa (Fig.
5A). In the isobaric study,
there are linear increases in the strain and the stress, which range
from 0.17 ± 0.05 to 0.95 ± 0.12 and from 2.73 ± 0.48 to 12.58 ± 1.45 kPa, respectively (Fig. 5B).
View larger version (19K):
[in this window]
[in a new window]
|
Fig. 5.
A: relationship between Kirchhoff's stress
( ) and bag volume (V) () and between Green's strain
() and bag volume () in the isovolumic distension
study (n = 9). The data are fitted by a least-squares
fit: = 0.50V + 6.4 (r2 = 0.93) and = 0.10V 0.25 (r2 = 0.99). B: relationship between esophageal wall stress and
intrabag pressure () and between strain and intrabag
pressure () in the isobaric distension study
(n = 8). The data are fitted by a least-squares fit:
= 0.21P + 1.01 (r2 = 0.96)
and = 0.016V + 0.005(r2 = 0.99).
|
|
The stress-strain relationship shows a nonlinear trend that can be
fitted by a polynomial (Fig. 6). The
relationship is fairly linear if the zero point is neglected. The slope
of the curve was 4.9 kPa (r2 = 0.94) for
the isovolumic study and 13.6 kPa (r2 = 0.95) for the isobaric study.
View larger version (20K):
[in this window]
[in a new window]
|
Fig. 6.
Relationship between Kirchhoff's stress and Green's
strain for the isovolumic () and isobaric
() studies. The data are fitted to a polynomial
equation in the isovolumic and isobaric distensions; = 7.233 23.582 + 27.56 + 0.46 (r2 = 0.99) and = 19.023 + 20.082 + 11.35 + 0.11 (r2 = 0.97),
respectively.
|
|
Dynamic changes of stress and strain.
The long period of esophageal distension with 15 ml volume or 40 mmHg
pressure reveals that there are dynamic changes in the intrabag
pressure, wall thickness, and esophageal luminal CSA during distension.
We observed two characteristic patterns. Pattern 1 is
characterized by a phasic increase in the bag pressure with an increase
in the esophageal luminal CSA without any significant change in the
wall thickness. During these instances, the wall stress and strain
increase with the increase in the pressure and CSA (Fig.
7A).
Pattern 2 consists of phasic changes in intrabag pressure
with a decrease in the CSA and an increase in the wall thickness,
suggesting contraction at the level of ultrasound probe. The esophageal
strain decreases with the reduction in the CSA. The wall stress,
however, either decreases or increases, depending on the degree of the
increase in wall thickness. If the increase in wall thickness is small,
the wall stress tends to increase while the strain decreases
(pattern 2a). On the other hand, if the increase in wall
thickness is large, the wall stress changes in parallel with the change
in the strain, as shown in Fig. 7B (pattern 2b).
View larger version (28K):
[in this window]
[in a new window]
|
Fig. 7.
A: an example of pattern 1. Top: dynamic change of the intrabag pressure by 15 ml during
a long period of distension. Middle: CSA ( )
increases and decreases in the same direction as the intrabag pressure.
The change in the wall thickness ( ) is unclear.
Bottom: stress () and strain
() are also changing dynamically in this distension
period and in the same direction. B: an example of
pattern 2b. Top: dynamic change in the intrabag
pressure during a 15-ml, long-period distension. Middle:
increase in the thickness () and the decrease in the
CSA () imply a contraction at the site of the bag
distension. Bottom: stress () is changing in
parallel with the change in the strain () in this
distension period.
|
|
The distribution of the different patterns in nine subjects with
sustained distension of 15 ml is as follows: pattern 1,
three subjects; pattern 2a, two subjects; pattern
2b, one subject; mixture of patterns 1 and
2a, two subjects (converting from 2a to
1). In one subject, no pattern could be identified. The
distribution of the different patterns in six subjects at 40 mmHg
isobaric sustained distension is as follows: pattern 1, no
subjects; pattern 2a, no subjects; pattern 2b,
five subjects; no pattern, one subject.
| |
DISCUSSION |
In vitro validation.
The in vitro studies confirm the accuracy of the measurements made by
the ultrasound technique. The position of the ultrasound probe inside
the bag and the angle between the probe and esophageal wall are
important variables to ensure adequate ultrasound images. The design of
our system for in vivo studies is such that it allows the placement of
the probe in the center of the bag. Because the esophagus is a
relatively straight tube, the angle between the transducer and the
esophageal wall is unlikely to be large. The accuracy of the
measurement is not compromised if the probe is slightly angled
(<15°). This is especially true because the measurements of the wall
thickness are made at four different positions around the circumference
and then a mean thickness is obtained. We often observed that the
esophageal wall was compressed by the aorta in one direction, resulting
in an asymmetrical wall thickness along the circumference.
In vivo studies.
The in vivo human studies show that the validated technique of
manometry and bag ultrasonography allows measurement of pressure, visualization of the CSA of the esophagus, and the measurement of wall
thickness. Our data show a linear relationship between esophageal
pressure, CSA, wall stress, strain, and elastic modulus (parameter of
wall rigidity) during esophageal distension. The magnitude of stress,
strain, and elastic modulus vary depending on the degree and method of
distension (isovolumic or isobaric). The reason for the difference
between isovolumic and isobaric distensions is most likely related to
the rate of the distension. Isovolumic distensions were performed by
manual injection with an approximate speed of injection of 2 ml/s. On
the other hand, isobaric distensions lasted until the CSA reached the
maximum size, which usually required 20-30 s. Rapid and slow
distensions caused different sensory and motor responses in human
rectum (22, 25, 27). Sun et al. (27) reported
that increasing the rate of inflation produced a graded increase in
pressure at each volume and suggested that time-dependent relaxation of
the smooth muscle is overcome at higher flow rates. Plourde et al.
(22) also reported that pressure-volume curves for slow
and rapid distensions are significantly different. It appears that
different mechanoreceptors are activated during rapid and slow rectal
distensions (17, 25). Ours is the first study in the
esophagus that shows the dependence of stress and strain on the method
of distension.
Phasic changes during distension.
One of the strengths of our technique is that it provides measurements
of the pressure, CSA, and wall thickness on a continuous-time basis.
The data shown in Figs. 3-6 correspond to the point of maximum relaxation following distension when the pressure is stable. During sustained esophageal distension, however, there are dynamic changes in
the intrabag pressure, CSA, and wall thickness, which result in dynamic
changes in the wall stress and strain. Distension-induced contraction at the site of bag is consistent with Orvar's study in
humans (18) that measured the luminal CSA and the
intraballoon pressure. Paterson et al. (20) also reported
phasic changes in the intraballoon pressure during distension in the
opossum esophagus; they described that the secondary contraction above the balloon squeezes the balloon and results in the fluctuation of the
intraballoon pressure. In our study, during some of the long
distensions, these pressure changes were associated with the changes in
the luminal CSA and the wall thickness of the esophagus and others were
not. The changes in wall thickness and luminal CSA as a result of
contraction around the balloon have never been described before. These
changes in the wall thickness resulted in different patterns of stress
and strain, although the distending stimulus was the same. The dynamic
nature of he stress-strain relationship in response to distension has
not been described before. The significance of such dynamic
relationships in normal healthy subjects is not known but must be
important to maintain the homeostasis of the esophageal wall during
various physiological functions. According to our classification,
pattern 1 shows no contraction but pattern 2 shows active contraction. Furthermore, within pattern
2, pattern 2b reveals stronger contraction than pattern 2a. A notable point is that the esophagus can
contract around a bag in the presence or absence of contraction above
the bag (pressure change at 2, 7, and 12 cm above the bag were
monitored in our study). This contraction appears to be phasic. In
future studies, analytical methods should be used to quantitatively
characterize these waveforms during distension.
Comparison with the other works.
Biancani et al. (2, 4) studied the biomechanics of the LES
and esophagus in animals and humans. They measured pressure by using
manometry, and the wall thickness was measured after killing the
animals or at the time of autopsy. One of the assumptions made by this
group was that there is no difference in the wall thickness in vitro
compared with the in vivo state. However, ultrasound recordings of the
esophagus show that the wall thickness in vivo strongly depends on the
tone of the muscle (9, 14, 21). Furthermore, during LES
and esophageal contraction there is an increase in the thickness of the
esophageal wall. Mayrand and Diamant (12) studied the
compliance of the esophagus by using a barostat technique. Although
compliance is an important parameter of the wall biomechanics, it does
not provide a measure of stress and elastic modulus (wall rigidity),
which are two important variables that may directly relate to motor and
sensory functions of the esophagus. The impedance planimetry, used by
Gregersen and his colleagues (5), provides information on
pressure and CSA of the esophagus but does not measure the wall
thickness. The combined high-frequency A-mode ultrasound-impedance
planimetry designed by Jorgensen et al. (8) addressed this
limitation and offers the measurement of wall thickness in vivo.
Jorgensen et al. formulated a uniaxial constitutive relationship in
terms of Cauchy's definition of stress and strain in the strain range
of ~0-200%. Cauchy's strain, however, should only be used in
small deformation (strain < 10%). Hence, their use of the small
strain measure is inappropriate. In the present study, we used Green's
strain and Kirchhoff's stress, which are the appropriate and
complementary pair for large deformation. Hence, we have further
improved Jorgensen's methodology by the use of B-mode ultrasonography
and improved the theoretical formulation to yield novel data on the
phasic deformation of the human esophagus during distension.
Model assumptions.
A number of assumptions were invoked in the computations of mean stress
and strain in the wall of the esophagus that deserve mention. The hoop
stress computed in Eq. 2 is defined as the force/area in the
circumferential direction. The underlying assumption is that there
exists an equilibrium of forces, i.e., the esophagus is either in a
static condition or, if it is in motion, the motion occurs with
constant velocity (the inertial forces due to acceleration are
considered negligible). It is obvious that the esophagus undergoes considerable geometric changes during contraction. The most reliable computations of stress are either at the point of complete relaxation or contraction at which the pressure is most stable. The values of
stress shown in Fig. 6 were made at the point of minimum
contraction at which the assumption of static equilibrium, i.e.,
no motion, is justified. It should be noted that the wall stress given
by Eq. 2 consists of the passive (due to the elastic and
viscoelastic properties of the tissue) and active (due to the muscle
contraction) stress. One of our future goals is to separate the passive
and active components.
Mechanical strain describes the deformation of a material. Any measure
of deformation or strain must be made in reference to the zero-stress
state of the tissue (3). It is impossible to determine the
zero-stress in vivo because even if the muscles are fully relaxed, the
tissue bears residual strain and stress (7). To reveal the
zero-stress state of the esophagus, a sufficient number of cuts must be
made to remove all of the internal stresses and strains. Because this
is not possible in human in vivo experiments, an estimation of the
zero-stress state has to be made. Some investigators have used small
distension at small pressure as the zero reference (23,
26). Recently, Patel et al. (19) calculated the
esophageal strain based on zero pressure in vivo. This unloaded (zero
pressure) state of the esophagus, however, still contains stress and
strain due to muscle tone. Mayrand et al. (12) show, in
human studies using the barostat technique, that smooth muscle tone has
an active component that can be reduced by a smooth muscle relaxant
such as amyl nitrate. In the present study, we used atropine to reduce the majority of tone. Atropine increased resting esophageal
circumference by ~15% and decreased the amplitude of swallow-induced
esophageal contraction by ~70% in the smooth muscle esophagus. This
implies a decrease in tone and diminished contractility, suggesting
that there is tonic cholinergic input to the esophageal body. The use of atropine more closely approximates the zero state. Even in the
complete absence of tone, however, some residual strain still exists in
the esophagus. Gregersen et al. (7) have previously shown
that the residual strains in the guinea pig are approximately 0.3 and
0.1 at the inner and outer surfaces of the esophagus, respectively.
Hence, the submucosa and muscle experience residual compression and
tension, respectively. The calculation of strain in the present study
must take into account the residual strain in the human esophagus when
those data become available.
Elasticity parameters.
A number of elasticity parameters have been previously defined to
characterize the mechanical properties of the esophagus. Compliance is
defined as the change in luminal dimension divided by the corresponding
change in pressure. This parameter merely expresses the differences in
luminal dimensions between pressure steps. Hence, it does not take into
account the actual degree of stretch or the wall thickness. Pressure
elastic modulus, a parameter for the wall stiffness, has been
calculated using the equation r × dP/dr, where r is the radius and
dP/dr is the changes in balloon pressure and
radius between two consecutive steps. Clearly, this is more
advantageous than compliance because it considers the degree of
stretch. However, its limitation is that it does not account for the
changes in wall thickness. The slope of the stress-strain relationship
(tangent modulus) takes into account the degree of stretch and the wall
thickness (3). Hence, it is a preferable measure of wall
rigidity. For a material with a linear stress-strain relationship
(i.e., Hookean material), the tangent modulus is called Young's
modulus. Our results show a linear stress-strain relationship in the
range of pressure (0-60 mmHg) and volume (5-20 ml) of the
distensions used. The relationship may become nonlinear in the low and
high regimes of stress and strain.
Critique of methods.
Our bag accommodates a maximum volume of 25 ml before the bag itself
contributed to the intrabag pressure. We found that with this size bag,
during volume distension of <5 ml, the bag was somewhat folded and
prevented complete visualization of the luminal CSA. For this reason,
we chose the outer esophageal circumference for calculations of strain
rather than inner esophageal circumference or midesophageal
circumference, which would theoretically be more appropriate.
During constant-volume distension, the manual injections were completed
in shorter time than during isobaric distension. The former may result
in a stronger secondary peristaltic contraction above the bag than in
the constant-pressure distension study. We computed a time for
calculation of the esophageal stress and strain when the pressure was
at the lowest value. There remains the possibility, however, that this
point did not reach a true minimum pressure.
Significance of study.
How does measurement of stress, strain, and wall rigidity help in our
understanding of the esophageal function? Mechanical properties of the
esophagus are an important determinant of tone, peristaltic reflexes,
bolus transport, mechanoreceptor responses, and sensory perception
(6). The stress-strain relationship is an expression of
the mechanical properties of the tissue. The roles of stress and strain
in the cardiovascular system have a firm foundation. It is well known
that stress and strain regulates the growth and remodeling of blood
vessels. For example, chronic exposure of the vessel wall to tensile
stress and strain (hypertension) leads to growth and "vascular
remodeling." In large-conduit arteries of the systemic circulation,
increased pressure and tensile stress is associated with smooth muscle
hypertrophy, increased media deposition of collagen, and destruction of
elastin fibers that leads to arterial stiffness, decreased compliance,
and increased flow impedance (11, 16). According to
Laplace's equation, the mean circumferential stress in the vessel wall
is directly proportional to the blood pressure and inversely
proportional to the vessel radius and thickness ratio. It appears that
the vessel wall thickness-to-radius ratio increases in proportion to
the increase in blood pressure so that the stress remains constant. We
recently found that, during esophageal contraction, as the esophageal
pressure increases so does the muscle thickness, which would indicate
that the wall stress remains relatively constant during contraction
(21). Furthermore, the remodeling of the esophagus in
various diseases [e.g., increase in the thickness of muscularis
propria in nutcracker esophagus and diffuse esophageal spasm (10,
15)] may well be in accordance with the "uniform stress"
hypothesis. A homeostatic state of stress must exist in an organ that
is closely regulated, and when homeostasis can no longer be maintained
the organ may fail. Congestive heart failure, aneurysm, and achalasia
of the esophagus are examples of the failure of the heart, blood
vessels, and esophagus, respectively. The mechanical characterization
of the esophagus in the normal subjects is thus crucial to the
understanding of the normal function of the esophagus and will serve as
a reference for understanding various pathological states. Furthermore,
distension of the esophagus and other viscera is a known stimulus that
induces esophageal and visceral sensation (13, 24). The
relationship between stress, strain, and esophageal sensation is not known.
| |
FOOTNOTES |
Address for reprint requests and other correspondence: R. K Mittal, Division of Gastroenterology 111D, VA Medical Center, Univ.
of California, San Diego, 3350 La Jolla Village Drive, San Diego, CA
92161 (E-mail: rmittal{at}ucsd.edu).
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/ajpgi.00394.2001
Received 7 September 2001; accepted in final form 26 November 2001.
| |
REFERENCES |
1.
Assentoft, JE,
Gregersen H,
and
O'Brien WD, Jr.
Determination of biomechanical properties in guinea pig esophagus by means of high frequency ultrasound and impedance planimetry.
Dig Dis Sci
45:
1260-1266,
2000[ISI][Medline].
2.
Biancani, P,
Goyal RK,
Phillips A,
and
Spiro HM.
Mechanics of sphincter action.
J Clin Invest
52:
2973-2978,
1973.
3.
Fung, YC.
Elasticity of soft tissues in simple elongation.
Am J Physiol
213:
1532-1544,
1967.
4.
Goyal, RK,
Biancani P,
Phillips A,
and
Spiro HM.
Mechanical properties of the esophageal wall.
J Clin Invest
50:
1456-1465,
1971.
5.
Gregersen, H,
and
Andersen MB.
Impedance measuring system for quantification of cross-sectional area in the gastrointestinal tract.
Med Biol Eng Comput
29:
108-110,
1991[ISI][Medline].
6.
Gregersen, H,
and
Kassab G.
Biomechanics of the gastrointestinal tract.
Neurogastroenterol Motil
8:
277-297,
1996[ISI][Medline].
7.
Gregersen, H,
Lee TC,
Chien S,
Skalak R,
and
Fung YC.
Strain distribution in the layered wall of the esophagus.
J Biomech Eng
121:
442-448,
1999[ISI][Medline].
8.
Jorgensen, CS,
Dall FH,
Jensen SL,
and
Gregersen H.
A new combined high-frequency ultrasound-impedance planimetry measuring system for the quantification of organ wall biomechanics in vivo.
J Biomech
28:
863-867,
1995[ISI][Medline].
9.
Liu, J,
Parashar VK,
and
Mittal RK.
Asymmetry of lower esophageal sphincter pressure: is it related to the muscle thickness or its shape?
Am J Physiol Gastrointest Liver Physiol
272:
G1509-G1517,
1997[Abstract/Free Full Text].
10.
Liu, J,
Pehlivanov N,
and
Mittal RK.
Correlation between esophageal muscle thickness and intraluminal pressures in DES: An ultrasonographic study (Abstract).
Gastroenterology
118:
1431,
2000.
11.
London, GM,
and
Safar ME.
Arterial wall remodeling and stiffness in hypertension: heterogeneous aspects.
Clin Exp Pharmacol Physiol
23, Suppl1:
S1-S5,
1996[ISI][Medline].
12.
Mayrand, S,
and
Diamant NE.
Measurement of human esophageal tone in vivo.
Gastroenterology
105:
1411-1420,
1993[ISI][Medline].
13.
Mertz, HB,
Naliboff J,
Munakata N,
Niazi N,
and
Mayer EA.
Altered rectal perception is a biological marker of patients with irritable bowel syndrome.
Gastroenterology
109:
40-52,
1995[ISI][Medline].
14.
Miller, LS,
Liu JB,
Klenn PJ,
Dhuria M,
Feld RI,
and
Goldberg BB.
High-frequency endoluminal ultrasonography of the esophagus in human autopsy specimens.
J Ultrasound Med
12:
563-566,
1993[Abstract].
15.
Mittal, RK,
Pehlivanov N,
and
Liu J.
The esophageal muscle thickness in patients with hypertensive esophageal peristalsis (Abstract).
Gastroenterology
118:
1430,
2000.
16.
Mulvany, MJ.
Resistance artery structure in hypertension: growth or remodeling?
J Cardiovasc Pharmacol
22, Suppl5:
S44-S47,
1993.
17.
Nguyen, P,
and
Castell DO.
Stimulation of esophageal mechanoreceptors is dependent on rate and duration of distension.
Am J Physiol Gastrointest Liver Physiol
267:
G115-G118,
1994[Abstract/Free Full Text].
18.
Orvar, KB,
Gregersen H,
and
Christensen J.
Biomechanical characteristics of the human esophagus.
Dig Dis Sci
38:
197-205,
1993[ISI][Medline].
19.
Patel, RS,
and
Rao SS.
Biomechanical and sensory parameters of the human esophagus at four levels.
Am J Physiol Gastrointest Liver Physiol
275:
G187-G191,
1998[Abstract/Free Full Text].
20.
Paterson, WG.
Neuromuscular mechanisms of esophageal responses at and proximal to a distending balloon.
Am J Physiol Gastrointest Liver Physiol
260:
G148-G155,
1991[Abstract/Free Full Text].
21.
Pehlivanov, N,
Liu J,
Kassab G,
Puckett JL,
and
Mittal RK.
Relationship between esophageal muscle thickness and intraluminal pressure: an ultrasonographic study.
Am J Physiol Gastrointest Liver Physiol
280:
G1093-G1098,
2001[Abstract/Free Full Text].
22.
Plourde, V,
Lembo T,
Shui Z,
Parker J,
Mertz H,
Tache Y,
Sytnik B,
and
Mayer E.
Effects of the somatostatin analogue octreotide on rectal afferent nerves in humans.
Am J Physiol Gastrointest Liver Physiol
265:
G742-G751,
1993[Abstract/Free Full Text].
23.
Rao, SS,
Gregersen H,
Hayek B,
Summers RW,
and
Christensen J.
Unexplained chest pain: the hypertensive, hyperreactive, and poorly compliant esophagus.
Ann Intern Med
124:
950-958,
1996[Abstract/Free Full Text].
24.
Richter, JE,
Barish CF,
and
Castell DO.
Abnormal sensory perception in patients with esophageal chest pain.
Gastroenterology
91:
845-852,
1986[ISI][Medline].
25.
Sabate, JM,
Coffin B,
Jian R,
Le Bars D,
and
Bouhassira D.
Rectal sensitivity assessed by a reflexologic technique: further evidence for two types of mechanoreceptors.
Am J Physiol Gastrointest Liver Physiol
279:
G692-G699,
2000[Abstract/Free Full Text].
26.
Storkholm, JH,
Villadsen GE,
Jensen SL,
and
Gregersen H.
Mechanical properties and collagen content differ between isolated guinea pig duodenum, jejunum, and distal ileum.
Dig Dis Sci
43:
2034-2041,
1998[ISI][Medline].
27.
Sun, WM,
Read NW,
Prior A,
Daly JA,
Cheah SK,
and
Grundy D.
Sensory and motor responses to rectal distention vary according to rate and pattern of balloon inflation.
Gastroenterology
99:
1008-1015,
1990[ISI][Medline].
Am J Physiol Gastrointest Liver Physiol 282(5):G785-G793
TOP
ABSTRACT
INTRODUCTION
