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J Physiol Volume 547, Number 2, 621-628, March 1, 2003 DOI: 10.1113/jphysiol.2002.028795
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J Physiol (2003), 547.2, pp. 621-628
© Copyright 2003 The Physiological Society
DOI: 10.1113/jphysiol.2002.028795

Effect of atropine on the biomechanical properties of the oesophageal wall in humans

Torahiko Takeda*, Ghassan Kassab†, Jianmin Liu*, Toshinaga Nabae* and Ravinder K. Mittal*

*Division of Gastroenterology, VA Medical Center, University of California, San Diego, CA 92161 and †Department of Biomedical Engineering, University of California, Irvine, CA 92697, USA

  ABSTRACT
Top
Abstract
Introduction
Methods
Results
Discussion
References

Recently, we reported a novel ultrasound technique to assess biomechanical properties of the oesophagus in human subjects. In the present study, we use the technique, in combination with atropine, to determine the active and passive biomechanical properties of the oesophagus in normal healthy humans. A manometric catheter equipped with a high-compliance bag and a high-frequency intraluminal ultrasonography probe was used to record pressure and oesophageal geometry. Oesophageal distensions with either isovolumic (5-20 ml water) or with isobaric (10-60 mmHg) technique were performed. Intra-bag pressure and ultrasound images of the oesophagus were recorded simultaneously. Following injection of atropine (15 µg kg-1, I.V.), the oesophageal distensions were repeated. The oesophageal wall compliance, circumferential wall tension, stress, strain and elastic modulus were calculated. Atropine resulted in an increase in the oesophageal wall compliance during isobaric distension, but no change in compliance was observed during isovolumic distension. The stress-strain relationship was found to be linear during both types of distension, before as well as after atropine. The Young's modulus, which is the slope of a linear stress-strain relationship, was significantly higher after atropine in the isovolumic study but not in the isobaric study. The stress-strain relationship of the active component (muscle contraction) was different during isovolumic and isobaric distensions but the passive components were similar. The passive and active stress-strain relationships of the human oesophagus resemble those of other soft biological tissues. Furthermore, the method of oesophageal distension has significant influence on the active but not the passive biomechanical properties due to a strain-rate effect.

(Received 18 July 2002; accepted after revision 10 December 2002; first published online 10 January 2003)
Corresponding author R. K. Mittal: Division of Gastroenterology 111D, VA Medical Center, University of California, San Diego, 3350 La Jolla Village Drive, San Diego, CA 92161, USA. Email: rmittal{at}ucsd.edu

  INTRODUCTION
Top
Abstract
Introduction
Methods
Results
Discussion
References

The effect of atropine, a smooth muscle relaxant, has often been determined as a change of compliance in the gastrointestinal (GI) tract. There are reports that atropine increases, decreases or has no effect on the compliance of the oesophagus in isovolumic distension studies (Barish et al. 1984; Richter et al. 1986; Paterson, 1991; Paterson et al. 1991a; Mayrand & Diamant, 1993; Mayrand et al. 1994). The compliance, however, is not an accurate measure of the wall stiffness. The elastic modulus, which is determined from the stress-strain relationship, is a more accurate measure of the wall stiffness. It has not been possible, however, to measure stress and strain in vivo in humans because previous methods could not measure wall thickness, luminal radius and pressure simultaneously. We recently developed a novel ultrasound technique that can measure all of the above-mentioned parameters simultaneously, in real time. Therefore, our technique allows accurate measurement of loading and deformation and subsequent computation of stress, strain and elastic modulus of the human oesophagus in vivo.

The oesophagus consists of several layers, mucosa, submucosa and muscularis propria. The latter consists of circumferential and longitudinal muscle fibres. The muscle layer has both passive and active properties consistent with the Hill's three elements model and the non-muscle tissue has only passive properties. The active contraction of the muscle can be described by a combination of 'contractile element' in series with an 'elastic element'. The passive component can be described by a 'parallel element'. The goals of our study were to determine: (1) the effect of atropine on the stress-strain properties of the human oesophagus under isovolumic and isobaric test conditions, and (2) the active and passive components of the wall stress properties of the human oesophagus.

  METHODS
Top
Abstract
Introduction
Methods
Results
Discussion
References

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 age of 32.7 years). Volunteers with a history of upper GI surgery, systemic diseases known to influence GI motility and volunteers that were taking medications which can affect the oesophagus were excluded from the study. 'The Human Research Protection Program of the University of California, San Diego' approved the study, which conformed with the standards set by the Declaration of Helsinki. Subjects gave written informed consent prior to participating in the study.

Measurement system

An oesophageal catheter assembly consisting of a 6.2F catheter equipped with a 20 MHz high-frequency intraluminal ultrasonography (HFIUS) probe, a manometry catheter, and a high-compliance polyvinyl bag was used for these studies (Takeda et al. 2002).

The length and maximum diameter of the bag were 5 cm and 3.5 cm, respectively. The volume of the bag could be increased to 25 ml without stretching the bag. This maximal volume of 25 ml was not exceeded in the in vivo studies, which ensured that the elastic properties of the bag itself did not contribute to the intra-bag pressure in the in vivo situation. The bag was designed in such a way that the HFIUS probe stayed in the centre of the bag during distension.

The manometric assembly had four side holes. One opening was located inside the bag and the other three were located at 2, 7 and 12 cm proximal to the bag. These three holes were perfused with distilled water at a rate of 0.5 ml min-1, using a low-compliance pneumohydraulic perfusion system (Arndorfer Medical Specialties Inc., Greendale, WI, USA). The pressure recordings from the four ports of the manometric catheter were inputted into a personal computer via a polygraph (Synectics Medical, Stockholm, Sweden). The ultrasound and manometric recordings were synchronized using a video timer.

Study protocol

Following a minimum of a 5 h fast, the volunteer's throat was sprayed with lidocaine HCl (lignocaine; Xylocaine Astra, Westborough, MA, USA). With the subject sitting in the upright position, the lubricated assembly was passed transnasally or transorally until the catheter tip was 60 cm from the nostril or 55 cm from the incisors. The subject was then placed in a semi-recumbent 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 oesophageal sphincter (LES) was identified as a high-pressure zone that relaxed in response to a swallow, and the LES location was noted in relation to the nostril or incisors. The centre 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 an adhesive tape.

After a rest period of 10 min, the bag was inflated quickly (rate of injection approximately 2 ml min-1), for at least 20 s, by injecting water into the bag using a hand-held syringe (isovolumic study done in 10 subjects). The infused volume was set at 5, 7.5, 12.5, 5, 10, 15, 20, 17.5 ml, in that order. Each volume was tested three times. Oesophageal images and pressures were recorded at the same time during an equilibrium pressure state. Oesophageal distensions using constant pressure technique (isobaric study conducted in 8 subjects) were also performed. The bag was distended with water at 20, 40, 60, 10, 30, 50 mmHg, in that order by connecting it with a saline reservoir. The latter was positioned at the desired vertical height to achieve the desired hydrostatic pressure. Each pressure was tested twice. Ten subjects participated in the isovolumic study and eight subjects in the isobaric study. The two types of study, isobaric and isovolumic distensions, were performed in a separate group of subjects. During bag distension, the subjects were asked to keep still, not to attempt to speak and to refrain from swallowing. Each of the oesophageal distensions was followed by a 30 s rest period. The isovolumic study and isobaric study were repeated after the injection of atropine (15 µg kg-1) through an antecubital vein.

Data measurements

The ultrasound (US) images were recorded in real time using a high-resolution ultrasound unit and a videotape recorder (Sony Corp., Tokyo, Japan). Measurements were made at a time point when the bag pressure reached a stable value, following injection of fluid in the isovolumic study. Similarly, a time point was selected for all measurements in the isobaric pressure study when the bag pressure reached a stable value. The ultrasound images were digitized on a personal computer, equipped with a high-definition video card (Targa+; Truevision, Inc., Indianapolis, IN, USA) and analysed using a commercially available image analysis software package (Mocha, Jandel Scientific, San Rafael, CA, USA). Images were displayed on a 17 inch, high-resolution monitor with pixel size of 640 times 480. This image magnification was approximately times12 (10 pixels = 1 mm). The perimeters of the bag and outer oesophageal wall were traced for each image using a computer program. The former corresponds to the inner circumference while the latter corresponds to the outer circumference of the oesophageal wall. Cross sectional area (CSA) of the lumen and the circumferential length of the oesophagus (ltheta) were measured. The total wall thickness (h) and the thickness of muscularis propria were measured (hm) at four quadrants around the circumference of the oesophagus. The circular radius of the lumen of the oesophagus (r) was calculated as r = (CSA/pi)1/2. Intra-bag pressure (P) at the time of the selected image for analysis was used for calculations.

Biomechanical analysis

Mechanical Parameters. The cross sectional area compliance (C) is defined as:

C = dCSA/dP, (1)

where CSA and P are the cross sectional area and pressure, respectively. The circumferential stretch ratio (lambdatheta) is given by:

lambdatheta = ltheta/Ltheta, (2)

where ltheta is the circumferential length of the oesophagus at a given distension and Ltheta the circumferential length at zero pressure after the injection of atropine (15 µg kg-1, I.V.).

The circumferential deformation of the oesophagus may be described by the Green's strain (epsilon), which is defined as follows:

epsilon = 1/2(lambdatheta2 - 1). (3)

Since the outer muscle wall can be easily identified in the US images, the outer wall strain was computed during distensions. The wall tension (T), at an equilibrium condition, is calculated according to Laplace's law:

T = Pr. (4)

The circumferential Kirchhoff's stress (sigma) in the oesophageal wall at a given distension is computed according to the following equation, with an assumption that the shape of the oesophagus is cylindrical:

sigma = (Pr)/(hlambdatheta2). (5)

The tangent modulus (E), a measure of stiffness, is given by the slope of Kirchhoff's stress-Green's strain relationship. If E is constant, it is referred to as Young's modulus.

Passive and active components of the stress-strain relationship. The circumferential oesophageal wall tension consists of two components: active tension (Ta) and passive tension (Tp). If atropine abolished smooth muscle contraction completely, the tension after the administration of atropine would correspond to the passive tension. Since atropine may not completely abolish the entire active component, the following formulation is required to extract the active and passive components. Assuming that the strength of swallow-induced contraction amplitude after atropine is given by a non-dimensional parameter f (a value of 0 implies complete relaxation and a value of 1 implies no relaxation of the smooth muscles), the total wall tension before atropine (Tba) and after atropine (Taa) can be given by:

Tba = Tp + Ta, (6a)

Taa = Tp + f Ta. (6b)

Since we experimentally determine Tba and Taa, eqn (6) can be solved for the passive and active tensions as:

Tp = (Taa - fTba)/(1 - f), (7a)

Ta = (Tba - Taa)/(1 - f). (7b)

The parameter f can be estimated as the ratio of the oesophageal contraction above the bag (upstream pressure) before and after the administration of atropine, i.e. if atropine completely abolished the upstream pressure, f would be equal to 0. Once the passive and active components of the tension are computed, we can calculate the active and passive Kirchhoff's stresses as follows:

sigmaa = Ta/(hmlambdatheta2), (8a)

sigmap = Tp/(hlambdatheta2), (8b)

where hm is the muscle thickness and h is the total wall thickness.

Statistical analysis

Results are expressed as means ± S.E.M. The data before and after atropine were compared using Wilcoxon's signed rank test. We did not obtain data for the higher volumes in those patients who developed pain and could not tolerate higher levels of bag distension.

  RESULTS
Top
Abstract
Introduction
Methods
Results
Discussion
References

One subject completed the pre-atropine portion of the isovolumic study but refused the injection of atropine. Ten subjects completed the entire isovolumic study and eight subjects completed the entire isobaric study (with and without atropine).

Effect of atropine

After administration of atropine, swallow-induced contraction amplitude was decreased by 72 %, as determined from the oesophageal pressure recording at 2 cm above the bag (82.9 ± 7.5 vs. 22.0 ± 2.2 mmHg). Hence, we assumed the value of f to be approximately 0.28. The circumferential length at zero pressure (Ltheta) increased significantly from 43.5 ± 1.5 to 49.8 ± 2.3 mm (P = 0.021) after injection of atropine.

Compliance

The relationships between intra-bag pressure and bag volume, and between luminal CSA and bag volume during the isovolumic study are shown in Fig. 1A and B, respectively. The data are fitted by a linear least squares fit: P = 2.73V + 19.6 (R2 = 0.98) and P = 2.54V + 3.3 (R2 = 0.97), before and after atropine, respectively. Intra-bag pressure was significantly lower after atropine at all distension volumes except for 15 and 20 ml, which showed no statistical significance. In the isovolumic study, luminal CSA increased linearly with bag volume (V) before (filled squares) and after (open squares) atropine. The data are fitted by a linear least squares fit: CSA = 31.0V - 48.0 (R2 = 0.99) and CSA = 24.5V + 2.8 (R2 = 0.99), before and after atropine, respectively. Luminal CSA after atropine was only significantly lower at the higher distension volumes (17.5 ml and 20 ml). The relationship between intra-bag pressure and luminal CSA in the isovolumic study was also linear before (filled squares) and after (open squares) atropine (Fig. 1C). The data are fitted by a linear least squares fit: CSA = 10.2V - 209.6 (R2 = 0.94) and CSA = 8.8V + 10.2 (R2 = 0.97), before and after atropine, respectively. Compliance after atropine tended to be lower than before atropine (P = 0.076).

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Figure 1. Isovolumic distensions

A, in the isovolumic study, intra-bag pressure (P) increased linearly with bag volume (V) before (filled square) and after (small square) atropine. B, in the isovolumic study, luminal CSA increased linearly with bag volume (V) before (filled square) and after (small square) atropine. Luminal CSA after atropine was only significantly lower at the higher distension volumes (17.5 ml and 20 ml), as denoted by the asterisk. C, the relationship between intra-bag pressure and luminal CSA in the isovolumic study is also linear before (filled square) and after (small square) atropine. Compliance tended to be lower than before atropine (P = 0.076).

Figure 2 shows that the relationship between intra-bag pressure (P) and luminal CSA in the isobaric study was linear before (filled squares) and after (open squares) atropine. The data are fitted by a linear least squares fit: CSA = 4.72P + 76.1 (R2 = 0.99) and CSA = 6.83P + 143.5 (R2 = 0.98), before and after atropine, respectively. Following administration of atropine, the CSA was higher for a given pressure as compared to pre-atropine, implying that the compliance was increased by atropine. Compliance after atropine was significantly higher than before atropine (P = 0.0099).

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Figure 2. Isobaric distension

The relationship between intra-bag pressure (P) and luminal cross sectional area in the isobaric study is linear before (filled square) and after (small square) atropine. Compliance after atropine was significantly higher than before atropine (P = 0.0099). The distensibility did not show a statistically significant difference before and after atropine.

Stress, strain and elastic modulus

The relationship between Green strain (epsilon) and Kirchhoff stress (sigma) shows a linear relationship before and after atropine, in the range of investigated strain in the isovolumic study (Fig. 3A). Young's modulus, given by the slope, was 4.9 and 11.1 kPa, before and after atropine, respectively. The difference between the two values was statistically significant (P = 0.037). In the isobaric study, we also found a linear relationship between stress and strain. The data are fitted by a linear least squares fit as sigma = 13.6epsilon + 1.0 (R2 = 0.95) (before atropine) and sigma = 14.2epsilon + 2.6 (R2 = 0.98) (after atropine) (Fig. 3B). There was no statistical difference between Young's modulus before and after atropine during isobaric distensions (13.6 and 14.2 kPa, respectively).

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Figure 3. Relationship between stress and strain during isovolumic and isobaric distensions

A, the relationship between Green strain (epsilon) and Kirchhoff stress (sigma) before (filled square) and after (small square) atropine in the isovolumic study. The data are fitted by a least squares fit: sigma = 4.9epsilon + 6.4 (R2 = 0.94) and sigma = 11.1epsilon + 0.9 (R2 = 0.93), before and after atropine, respectively. Young's elastic modulus, given by the slope, is significantly higher after atropine (P = 0.037). B, relationship between Green strain (epsilon) and Kirchhoff stress (sigma) before (filled square) and after (small square) atropine in the isobaric study. The data are fitted by a least squares fit: sigma = 13.6epsilon + 1.0 (R2 = 0.95) and sigma = 14.2epsilon + 2.6 (R2 = 0.98), before and after atropine, respectively. There is no statistical difference between Young's elastic modulus before and after atropine.

Passive and active tension

The tension-stretch ratio relationship showed a non-linear trend that could be fitted by a third polynomial before and after atropine in isovolumic (Fig. 4A) and isobaric studies (Fig. 4B). Based on eqns (8a) and (8b) presented in the Methods section, the data can be resolved into active and passive components of the length-tension relationship for the isovolumic and isobaric studies (Fig. 5 and Fig. 6, respectively). In order to compute the stress-strain relationships for the active and passive properties, muscle thickness before atropine, and total wall thickness after atropine were measured with each distension volume and pressure in both studies. These wall thickness-stretch ratio relationships were fitted by a straight line, using a least squares fit, and were used to compute the active and passive component of the stress according to eqns (8a) and (8b). The stress-strain relationship for the passive properties shows a non-linear pattern for both isovolumic and isobaric distensions, suggesting that the passive tissue stiffness increased at higher strains and was not dependent on the method of distension (Fig. 6). On the other hand, the active component of the stress-strain relationship revealed differences between the two types of distensions. The isovolumic curve shows a parabolic trend with the maximal active stress occurring at a strain of approximately 0.4 (Fig. 5). In contrast, the maximal active stress during isobaric distension was not realized in the range of strains investigated.

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Figure 4. Relationship between tension and stretch ratio during isovolumic and isobaric distensions

A, relationship between stretch ratio (lambda) and tension (T) before (filled square) and after (small square) atropine in isovolumic study. The data are fitted to a 3rd polynomial equation before and after atropine; Tb = 60.4lambda3 - 254.3lambda2 + 458.3lambda - 264 (R2 = 0.99) and Ta = 49.7lambda3 - 129.4lambda2 + 155.8lambda - 76.0 (R2 = 0.99), respectively. B, relationship between stretch ratio (lambda) and tension (T) before (filled square) and after (small square) atropine in the isobaric study. The data are fitted to a 3rd polynomial equation before and after atropine: Tb = 4.6lambda3 + 104.6lambda2 - 224.9lambda + 115.4 (R2 = 0.99) and Ta = 62.1lambda3 - 122.8lambda2 + 102.2lambda - 41.4 (R2 = 0.99), respectively.

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Figure 5. Relationship between stress and strain for the contractile elements of the oesophageal wall during isovolumic and isobaric distensions

The active components of stress-strain relationship in the isovolumic (continuous line) and in the isobaric (dotted line) study.

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Figure 6. Relationship between stress and strain for the passive (visco-elastic) elements of the oesophageal wall during isovolumic and isobaric distensions

The passive components of stress-strain relationship in the isovolumic (continuous line) and in the isobaric (dotted line) study.

  DISCUSSION
Top
Abstract
Introduction
Methods
Results
Discussion
References

Elasticity parameters

A number of elasticity parameters have been previously defined to characterize the mechanical properties of the oesophagus. 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, defined as r times dP/dr, where r is the radius, dP/dr are the changes in bag pressure and radius between two consecutive steps has also been previously employed. Clearly, pressure elastic modulus is more advantageous than compliance because it considers the degree of stretch. However, its limitation is that it does not take into account the changes in the wall thickness. The slope of the stress-strain relationship (tangent modulus) takes into account the degree of stretch and the wall thickness (Gregersen & Kassab, 1996). 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. However, the relationship may become non-linear in the low and high range of stress and strain.

Effect of atropine on compliance

The effect of atropine, a smooth muscle relaxant, on smooth muscle oesophagus is controversial. Paterson et al. reported that atropine did not affect the intra-bag pressure in their isovolumic study with air distension using opossum and human oesophagus (Paterson, 1991; Paterson et al. 1991b). To the contrary, Barish et al. (1984) reported that atropine diminished the intra-bag pressure in their isovolumic air distension study. Mayrand et al. (1994) reported, in their isobaric study using cats, that although the compliance (slope of the volume-pressure relationship) after atropine was slightly greater than control, this difference was not statistically significant. Our study shows a unique difference between isovolumic and isobaric distensions. In the isovolumic study, compliance tended to be lower after atropine, while in the isobaric study, it was higher. Our result is consistent with the earlier report, which reported that the smooth muscle relaxant, amyl nitrate, increased compliance in the human smooth muscle oesophagus in vivo during isobaric distension (Mayrand & Diamant, 1993). It should be noted that a parallel shift in the P-CSA relationship does not constitute a change in compliance. A change in compliance is only dictated by the change of slope.

Effect of atropine on oesophageal tone

The GI tract is a reasonably uniform cylinder, essentially a deformable tube. Therefore, it makes geometric sense to define tone as a sustained reduction in luminal cross sectional area and circumference, or surface area (Gregersen & Christensen, 2000). Our data show an increase in oesophageal circumference, by approximately 15 %, after atropine and suggests that there is indeed a tonic cholinergic input to the distal oesophagus.

Effect of atropine on stress-strain relationship

The Young's modulus increased after atropine in isovolumic study. On the other hand, in the isobaric study, it did not change significantly. These results suggest that atropine behaves as if it stiffens the oesophageal body in an isovolumic but not an isobaric study. Why does atropine behave in different ways depending on the modality of oesophageal distension? To answer this question, we separated the passive from the active components of the stress. Stress is the force per unit area; strain, on the other hand, is a dimensionless measure of deformation. A non-linear stress-strain relationship describes the material properties of a tissue that does not contain muscle elements. Muscle, however, has the capacity to develop active force, i.e. contraction, in response to applied stress, which creates two kinds of stress, one arising from the passive physical properties of the tissue and the other as the result of activation of the contractile apparatus of the muscle. In the present study, we computed the contribution of the active and passive components of the stress-strain curves. The interesting observation is that the active muscle reacts in different ways in the isovolumic and isobaric studies, while the passive component of the stress behaves very similarly.

Why then did our isovolumic and isobaric distensions induce different active stresses? Our isovolumic distensions were performed by manual injection with an approximate speed of 2 ml s-1 (2.5-10 s), while isobaric distensions lasted until the CSA reached the maximum size and usually required about 20-30 s. Therefore, our isovolumic distension is equivalent to rapid distension and isobaric to slow distension. Several reports indicate that rapid and slow distension cause different sensory and motor responses in the human rectum (Sun et al. 1990; Plourde et al. 1993; Sabate et al. 2000). Sun et al. (1990) reported that increasing the rate of rectal inflation produced graded increase in pressure at each volume, suggesting that time-dependent relaxation of smooth muscle is overcome at higher flow rates and they proposed that superficial mucosal and deeper musculo-serosal mechanoreceptors are preferentially activated by slow-ramp and rapid phasic rectal distensions. Plourde et al. (1993) also reported that pressure-volume curves for slow and rapid distension were significantly different. Sabate et al. (2000) hypothesized that the different rectal mechanoreceptors are activated during rapid and slow rectal distension. Although such a reflexive relaxation to bag distension in the oesophagus has not been reported yet, a report from Nguyen & Castell (1994) suggests that this difference may exist even in the oesophagus. Our data, for the first time, demonstrate such a difference in the biomechanical properties of the oesophagus caused by the applied strain rate. Unlike the active mechanical properties which are strain-dependent, the passive properties of biological tissues are known to be relatively insensitive to strain rate. Previous studies have shown that a four-order-of-magnitude change in strain rate causes only a twofold change in the stress-strain relationship (Fung, 1993), which is consistent with our observations (Fig. 6).

Isometric vs. isotonic contractions

In addition to the differences in the rates of distension between the two protocols, the isovolumic and isobaric experiments correspond to isometric and isotonic contractions, respectively. In the isovolumic studies, the oesophagus contracts against a bag which contains an incompressible fluid. Hence, the dimensions of the oesophagus do not change significantly while the pressure in the bag does; i.e. isometric contraction. In the isobaric experiment on the other hand, the bag pressure is set by a column of fluid whose height does not change significantly as the fluid is squeezed out of the bag. Hence, the geometry of the oesophagus changes while during the oesophageal contraction the pressure remains constant; i.e. isotonic contraction. It should be noted however, that the initial contraction of the oesophagus in the isobaric experiment is isometric since sufficient pressure needs to be generated to displace the fluid. Furthermore, the last part of the contraction in the isobaric experiment is also isometric since the oesophagus may completely collapse the bag and hence no additional deformation of the oesophagus can occur.

Atropine-induced stiffness

Atropine causes relaxation of both circumferential and longitudinal muscle of the oesophagus in the resting state (prior to distension). Relaxation of the circular muscle should cause a decrease in wall stiffness. Relaxation of the longitudinal muscle increases the length of the oesophagus (unpublished observation), the effect of which on the oesophageal wall stiffness is not known. Several observations suggest that an increase in the length of the oesophagus can increase its wall stiffness. Assentoft et al. (2000) reported that the stress-strain curve for the elongated state was shifted to the left, indicating that the stiffness of the oesophageal wall increased after elongation of the oesophagus in the guinea-pig. The notion that lengthening of a tube increases its wall stiffness has been demonstrated in blood vessels (Cox, 1975; Weizsacker et al. 1983; Von Maltzahn et al. 1984; Dobrin, 1986; Humphrey et al. 1993). Similar behaviours are exhibited by most soft tissues under biaxial loads (Humphrey et al. 1987, 1990, 1992). Our observation that the wall stiffness increases after atropine suggests that in vivo, the effect of atropine on longitudinal muscle is a more important determinant of the total wall stiffness than the effect on the circular muscle.

Summary and conclusions

In summary, we report the effects of atropine on the biomechanical properties of the human oesophagus in vivo using a state of the art methodology. Our findings suggest that the method of oesophageal distension has a significant influence on the active but not the passive elements of biomechanical properties of the oesophagus. We suggest that the isovolumic distension is more physiologically relevant and results in a typical parabolic shape for the tension-length relationship. In isovolumic distension, we found that the compliance decreased and the Young's modulus increased, which implies that the oesophagus becomes more rigid in the circumferential direction.

Future studies

Patients with primary motor disorders of the oesophagus have an increase in the thickness of muscularis propria of the oesophagus (Pehlivanov et al. 2002), which is likely to have a major influence on its biomechanical properties. We speculate that the differences in the biomechanical properties of the oesophagus between normal subjects and patients may be important determinants of the oesophageal sensory (Richter et al. 1986) and motor dysfunction (Pehlivanov et al. 2002) in the patient group, which will be the subject of our future studies.

  REFERENCES
Top
Abstract
Introduction
Methods
Results
Discussion
References

Assentoft JE, Gregersen H & O'Brien WD (2000). Determination of biomechanical properties in guinea pig oesophagus by means of high frequency ultrasound and impedance planimetry. Dig Dis Sci 45, 1260-1266 [Medline]
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