1 Department of Mechanical Engineering, Pennsylvania State University, University Park, Pennsylvania 16802; 2 Department of Biomedical Engineering and Medical Informatics, Swiss Federal Institute of Technology, Zurich; 3 Department of Gastroenterology, University Hospital, Zurich, Switzerland; and 4 Division of Gastroenterology, Royal Adelaide Hospital, Adelaide, Australia
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ABSTRACT |
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The relative contributions to gastric emptying from common cavity antroduodenal pressure difference ("pressure pump") vs. propagating high-pressure waves in the distal antrum ("peristaltic pump") were analyzed in humans by high-resolution manometry concurrently with time-resolved three-dimensional magnetic resonance imaging during intraduodenal nutrient infusion at 2 kcal/min. Gastric volume, space-time pressure, and contraction wave histories in the antropyloroduodenal region were measured in seven healthy subjects. The subjects fell into two distinct groups with an order of magnitude difference in levels of antral pressure activity. However, there was no significant difference in average rate of gastric emptying between the two groups. Antral pressure history was separated into "propagating high-pressure events" (HPE), "nonpropagating HPEs," and "quiescent periods." Quiescent periods dominated, and average pressure during quiescent periods remained unchanged with decreasing gastric volume, suggesting that common cavity pressure levels were maintained by increasing wall muscle tone with decreasing volume. When propagating HPEs moved to within 2-3 cm of the pylorus, pyloric resistance was found statistically to increase with decreasing distance between peristaltic waves and the pylorus. We conclude that transpyloric flow tends to be blocked when antral contraction waves are within a "zone of influence" proximal to the pylorus, suggesting physiological coordination between pyloric and antral contractile activity. We further conclude that gastric emptying of nutrient liquids is primarily through the "pressure pump" mechanism controlled by pyloric opening during periods of relative quiescence in antral contractile wave activity.
gastric motility; peristalsis; pressure wave; contraction wave; pump; mechanics
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INTRODUCTION |
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ALTHOUGH ANIMAL STUDIES indicate that
gastric emptying is often pulsatile and that the pylorus is important
in regulating the rate of gastric emptying (1, 13, 20, 21), the
patterning of antral motor and pressure events, their coordinations
with pyloric opening, and their relative contributions to gastric
emptying in humans are not well understood. For example, intermittent
transpyloric flow could, in principle, be created by intermittent
increases in antral pressure in the presence of relatively constant
pyloric resistance or by intermittent pyloric opening in the presence of a relatively constant antroduodenal pressure difference
(PA PD). Alternatively,
gastric emptying could, in principle, be controlled more intelligently
by neuromuscular coordination (3), or discoordination (14), of pyloric
opening, with phasic increases in transpyloric pressure
difference induced by antral contractile activity. The relative
contributions of common cavity and phasic transpyloric pressure
differences, the role of the pylorus in regulating transpyloric flow,
and the variations in these components with meal composition and volume
have not been well delineated in humans (4, 8). With recognition that
the direction and magnitude of transpyloric flow follow, from basic
fluid mechanical considerations (2, 11, 12), from transpyloric pressure differences across an open pylorus, there is much gastric physiology to
be learned by detailed quantitative analysis of coordinated pressure
and imaging data.
Mechanically, time-local components of gastric emptying may be grouped
roughly within "peristaltic pump" or "pressure pump" contributors to transpyloric flow. To better understand this
distinction and the analyses that follow, we sketch in Fig.
1 localized antroduodenal pressure changes
induced by progressive antral contraction waves superposed on common
cavity pressure variations arising from global changes in gastric wall
muscle tone. Because transpyloric flow can only occur during periods of
positive PA PD, phasic changes in
positive transpyloric pressure difference localized to the distal
antrum are shown in Fig. 1B (solid line, hatched area) rising
from a baseline of more gradual changes in PA
PD associated with the common cavity component (dashed
lines). The phasic changes in transpyloric pressure difference are part
of a propagating pressure wave (hatched pressure curves P1
and PA) resulting from localized peristaltic contraction
waves (Fig. 1A), whereas the changing baseline pressure
in the distal antrum is common to the entire contiguous
stomach (dashed pressure curves P1, P2, and PA) and may arise from changes in muscle tone anywhere on
the gastric wall, including, for example, the fundus.
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The peristaltic pump contribution to gastric emptying occurs during the
short-duration periods of pressure increase just proximal to the
pyloric channel induced by an advancing contraction wave when the
pylorus is open. The volume of transpyloric flow during these
peristalsis-induced increases in PA PD depends on the magnitude and duration of phasic pressure
increase and on the resistance to flow within the pyloric channel.
Depending on the diameter of the pyloric channel, flow
is directed aborally and orally during phasic increases in antral
pressure. If the pylorus is closed, for example, all flow is directed
orally and no transpyloric flow occurs. If pyloric resistance is
controlled so that the pylorus is fully open as the antral
contraction wave advances, on the other hand, optimal contribution to
transpyloric flow from antral contractile activity results.
The pressure pump contributor to gastric emptying is associated with
flow during periods of relative quiescence in contraction-induced pressure activity in the distal antrum (dashed lines in Fig.
1B). Like the peristaltic pump contribution, the rate of
transpyloric flow depends on the magnitude of the common cavity
PA PD and the
resistance to flow, as determined by the diameter of the pyloric channel during the quiescent periods.
The relative contributions of peristaltic and pressure pumps to gastric
emptying depend on several factors, including the coordination between
pyloric opening and phasic pressure excursions in the distal
antrum, the degree and duration of opening of the pyloric channel
during quiescent periods, and the magnitudes of PA PD during pyloric opening periods. Furthermore, the
combination of motor events responsible for emptying depends on
physiological responses to the composition of the meal, to gastric
volume, and to pharmacological substances that alter gastric or
duodenal sensory function (4, 8). In this study we analyze local
contributions to emptying delayed by controlled nutrient infusion in
the proximal duodenum.
The aim of the present study is to assess the relative contributions to gastric emptying of the pressure and peristaltic pumps in humans during emptying of nonnutrient saline, with the rate of emptying delayed by controlled intraduodenal nutrient infusion. To analyze these primary contributors to gastric emptying, we have concurrently assessed intragastric pressure using high-resolution high-accuracy manometry (6) and antropyloroduodenal anatomy with three-dimensional magnetic resonance (MR) imaging (MRI) (15, 17).
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METHODS |
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Concurrent MRI and high-resolution manometry studies were performed on seven healthy subjects (5 men and 2 women) 23-45 yr of age. All subjects gave written informed consent, and the study was approved by the Ethics Committee of the University Hospital, Zurich. The data were subsequently analyzed using various statistical measures.
Concurrent MRI and High-Resolution Manometry
Subjects fasted overnight before the study. The manometric assembly (4-mm OD) and a second tube (2.5-mm diameter, used for intragastric instillation of saline) were passed into the stomach via an anesthetized nostril. The manometric assembly was positioned across the pylorus by use of transmucosal potential difference (PDTM; see below). After phase III of the interdigestive migrating motor complex, an intraduodenal infusion commenced. The infusion consisted of a nutrient liquid (equal volumes of 25% dextrose and 10% Intralipid, 1.1 kcal/ml; Kabi-Vitrum, Stockholm, Sweden) delivered at the rate of 2 ml/min (2.1 kcal/min) for the remainder of the study. After 30 min of infusion, the subject was transferred to the MR scanner and positioned lying 30° to the right side to ensure filling of the antrum. An isotonic saline solution (750 or 500 ml) was then infused into the gastric lumen over ~4 min. The saline was marked with 600 µM Gd-labeled tetraazacyclododecane tetraacetic acid (Laboratiore Guerbet, Aulnay-sous Bois, France) as a contrast agent for MRI. All MRI studies were performed using a Philips Gyroscan ACS-NT 1.5-T whole body scanner.Figure 2 summarizes the protocol. Within
2-3 min after the stomach was filled, an MR "volume scan"
was performed to measure the volume of liquid in the stomach. Two
additional volume scans were performed 15 and 30 min later to assess
the rate of gastric emptying. Between each pair of volume scans, three
"motility scans" were carried out to assess changes in
antropyloroduodenal anatomy over time. Manometric pressures were
recorded uninterrupted throughout the study with the exception of
periodic short periods for recalibration of manometric reference
pressure (6). All analysis was carried out for data collected during
the 30-min period after gastric filling.
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Volume scans. To determine intragastric liquid volume, a Turbo Spinecho scan (repetition time = 576 ms, echo time = 12 ms) with 24 contiguous slices (7.5-mm slice thickness) was acquired over 60 s by a previously established methodology (16). In-plane pixel resolution was 1.5 mm (256 × 256 pixels, field of view = 384 mm). To minimize motion artifacts, the scan was divided into four periods of 15 s each, and the subjects were asked to hold their breath during each period. The measured volume necessarily included the ingested liquid and the gastric secretion.
Motility scans. To assess antropyloroduodenal motility and pressure-geometry relationships, rapid multiplanar scans were carried out over multiple 90-s periods. Seven slices were acquired per second by use of a multislice gradient echo planar imaging (EPI) sequence (coronal angulated orientation, EPI factor = 5, echo time = 5 ms, repetition time = 81 ms, flip angle = 20°, matrix size = 128 × 128 pixels, resolution = 3 mm, field of view = 384 mm, slice thickness = 7 mm). The scan was triggered by a signal from the computer controlling manometric data acquisition to synchronize MRI with manometry.
A perfusion manometry system (Dentsleeve) with optimized electronics (transducer drift <0.1 mmHg/15 min; Sedia, Fribourg, Switzerland) was used to record pressures along a catheter with 21 ports (0.4-mm lumen diameter, 4-mm OD), 19 of which were used for pressure in this study and 1 for intraduodenal nutrient infusion, as illustrated in Fig. 3. The catheter was preflushed with CO2 to eliminate air bubbles, and water perfusion was limited to 0.08 ml/min. To obtain high spatial resolution through the antropyloroduodenal region, the 19 pressure-recording ports were spaced 3.3 mm apart along a 6-cm segment of the assembly. The 3rd and 17th side holes were perfused with normal saline from separate reservoirs, and PDTM was measured concurrently with manometry to aid the positioning of the catheter across the pylorus. To identify the position of the catheter on MR images, two small stainless steel markers were placed on the catheter at each end of the 19-hole array. The manometric data were recorded for the entire duration of the study at 8 samples/s. Transducer drift was regularly corrected over the study period with use of an underwater reference, and measurement uncertainty was minimized to within 0.5 mmHg (6). The infusion port was ~14 cm below the pylorus.
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Data Analysis Methods
The data analyzed were limited to times during which the PDTM readings indicated correct placement of the catheter across the pyloric channel (7). Pressure data were analyzed using several statistical techniques, as described below. In preliminary analysis, it was determined that stable statistics for pressure differences required ~4 min of data (2,000 samples collected at 8 samples/s). Thus the analysis was extended beyond the 90-s motility scale periods to include the entire contiguous 30-min period of pressure data.Statistical analysis of pressure characteristics associated with
transpyloric flow required accurate determination of the location of
the pylorus along the catheter as a function of time. To this end, the
manometric data were interpolated between ports by use of cubic splines
and plotted as contours of constant pressure ("isocontours"), as
shown in Fig. 4. During intraduodenal
nutrient infusion, a relatively well-defined band of high pressure was observed in the isocontour plots for all subjects, extending
~6-10 mm along the lumen.
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Antral, pyloric, and duodenal ports. Figure 4 includes points (with error bars) marking the pyloric location identified from the MR images during motility scan periods, illustrating the correspondence between the high-pressure band and pyloric channel. A separate quantitative analysis (5) confirmed that the high-pressure band corresponded to the anatomic pylorus as determined from the MRI scans. Therefore, because our statistical analyses of pressure used the entire pressure signal, we defined the "pyloric port" as the manometric port closest to the local maximum in pressure within the high-pressure band. The proximal and distal extremities of the pyloric channel were subsequently identified by the "antral port" and "duodenal port," defined as the manometric ports 1 cm proximal and 1 cm distal to the pyloric port, respectively. Because the antral, pyloric, and duodenal ports are defined relative to the space-time distribution in antropyloroduodenal pressure, the catheter side holes that define these ports can change with time. Comparison with the MR images confirmed that the ports 1 cm proximal and distal to the pyloric port were within the distal antrum and proximal duodenum, respectively, as also indicated by the pressure isocontours of Fig. 4.
Basal pressures.
Antral, pyloric, and duodenal basal pressures
(P*A,
P*P, and
P*D) were defined as the average values
of the lowest 5% of the manometric pressures recorded in the antral,
pyloric, and duodenal ports, respectively, over the entire data period,
with exclusion of recalibration and PDTM
misalignment periods. (As a check, P*A
was also calculated by including all antral channels. The
difference between the two approaches was within the imprecision of the
measurement.) Because gastric emptying is associated with
PA PD, all pressures were
referenced to P*D unless
otherwise indicated. Relative P*P and
P*A are catalogued in Table
1.
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Level of antral pressure activity.
We quantify the differences in levels of phasic and nonphasic pressure
activity between subjects in relation to the existence of
"high-pressure events" (HPEs), where an HPE is defined as a group
of pressure values in any antral channel that exceed a predefined fixed
threshold relative to P*A. That is, an
HPE is a channel-specific period where P P*A exceeds a predefined value
PHP
P*A. Because these
periods were used for comparison between subjects, the threshold
PHP
P*A was set to
the same level for all subjects. We discuss below our basis for
choosing the particular HPE threshold, PHP
P*A = 5 mmHg. Antral pressure
activity in individual subjects was then quantified using the following
statistical measures.
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"Active" periods, "quiescent" periods, and "propagating HPEs." To contrast the relative contributions to gastric emptying of progressive antral pressure events (peristaltic pump) with the intermediate periods of relative quiescence (pressure pump), we first separated antral pressure-time history into subject-specific "high" and "low" pressure periods by using the "shoulder" pressure (PSP), as described in the APPENDIX. The definition of PSP follows from the pressure-time history in the distal antrum in individual subjects, which, as in Fig. 6A, has the structure of spikes of high-pressure activity rising from a bed of low-level pressure fluctuations. As described in detail in the APPENDIX, PSP is an objective measure of pressure, obtained from the "cumulative frequency distribution" (see Fig. 11) that defines the transition between the lower-level pressure fluctuations and the higher, spikier pressure events in the antral pressure port.
As shown in Table 1, relative PSP (PSPWindow means.
The time mean of a quantity X (where X could be, e.g.,
pressure or pressure gradient) was defined over specified
periods, excluding periods where the PDTM readings
indicated incorrect placement of the catheter across the
pyloric channel. To assess the variation of basal and mean pressure
with time, we divided the data period into shorter time
intervals, or "windows," and computed the mean and
basal pressures within each window. The minimum time interval had to be
sufficiently long to contain enough sample for stable statistics. Tests
suggested that 2 min of sample (1,000 at 8 samples/s) were required
for stable pressure statistics (4 min for pressure difference). Thus
the total time interval was separated into three time
windows with
2,000 pressure samples in each window. Basal
pressure and time averages were computed for each time window.
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RESULTS |
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Emptying vs. High-Pressure Activity in the Antrum
In Table 2, subjects are numbered from the highest to the lowest gastric volumes emptied during the first 30 min after gastric filling. The volume of gastric emptying (VGE) differed widely among subjects, and the average pressure during HPEs varied from 5.7 to 12.0 mmHg above P*A with no correlation with volume emptied. However, AUCmax varied from 60 to 1,660 mmHg · s in such a way that all subjects could be clearly separated into high and low antral pressure activity groups (Fig. 5), where AUCmax was 9-10 times lower in the low-pressure activity group (subjects 1, 3, and 4) than in the high-pressure activity group (subjects 2, 5, 6, and 7). Correspondingly, the total durations of HPEs were significantly higher in the high antral pressure activity group (Table 2). As indicated in Table 3, the low-activity subjects displayed no propagating HPEs, and a significantly higher percentage of time was occupied by quiescent periods [98 ± 2.8 vs. 76 ± 9.4% (SD)] in the low-activity group. Nevertheless, Fig. 5 indicates that the volume of liquid emptied was higher, on average, in the low-pressure activity group (251 and 408 ml in the high- and low-activity groups, respectively). The correlation coefficient between VGE and AUCmax was
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Figure 4 compares the space-time pressure history during a 90-s motility scan period in members of the low- and high-activity groups. Whereas Fig. 4A shows relatively little high-pressure activity proximal to the pyloric channel, Fig. 4B shows clear high-amplitude peristaltic pressure wave activity. These time-space pressure characteristics were typical of the two groups.
Figure 4B also shows the termination of the antral pressure waves ~1 cm preceding the pyloric channel, creating a gap of low pressure. The length of this "low-pressure gap" is tabulated in Table 2 for the four "high-activity" subjects. Subject 6 differed from the other three high-activity subjects (subjects 2, 5, and 7), in that the low-pressure gap was over twice as wide (3.1 cm for subject 6 vs. 1.4, 1.3, and 1.6 cm for subjects 2, 5, and 7). This difference affects subsequent statistics (see below).
Basal and Mean Pressures and Pressure Gradient
Figure 6 shows a representative example of time history of antral, pyloric, and duodenal pressures measured from the antral, pyloric, and duodenal ports over ~30 min for high-activity subject 2. All pressures are referenced to P*D. Particularly evident in antral and pyloric pressure are intermittent spikes in pressure overlying low-level pressure fluctuations. Also evident is the overall higher baseline pressure in the antrum than in the duodenum (Table 1).
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To assess the overall changes in background pressure during gastric
emptying, we plot in Fig. 7 average antral
and pyloric port pressures measured within the quiescent periods in
each of three time windows spanning the ~30-min data periods (see
METHODS). Whereas the quiescent period was defined in the
antral port by using the 5-mmHg threshold described in
METHODS, in the pyloric port the quiescent periods of
pyloric pressure were defined using the PSP in that port
(see METHODS and APPENDIX).
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In Fig. 7, pressures are referenced to
P*A (Table 1). Figure 7 indicates that
the average pressures during quiescence in the antral and pyloric
channels are on the order of 2 mmHg above
P*A. More importantly, there was no
significant change in average antral and pyloric pressure during the
periods of quiescence during the 30-min periods of gastric emptying
(P 0.6).
We also found statistically insignificant changes in windowed mean basal pressure over the 30-min period averaged over the seven subjects (not shown). We found, by examining in detail the changes in P*A and quiescent pressure from the first to the third window, that those subjects with a small increase or decrease in average pressure during periods of quiescence also had a corresponding small increase or decrease in basal pressure, suggesting that the average quiescent period pressure in the antrum is correlated with P*A.
The mean pressure gradient across the pyloric channel from the antral to the duodenal port averaged over all subjects was 0.3 ± 0.2 (SD) mmHg/cm.
Antral-Pyloric Pressure Relationships
In Fig. 4B, the periods when progressive antral pressure waves exist appear to be also periods of high pyloric pressure. This subjective observation is made clearer in Fig. 8, where the active and quiescent periods are shown in the pyloric channel and in the first three antral channels (Fig. 7). In the pyloric port the quiescent periods are those with the least pyloric resistance and, therefore, are the most likely to allow transpyloric flow. We observe that during this 90-s period the pyloric quiescent periods occur during periods of quiescence also in the antral channels and that the resistance to transpyloric flow appears to be highest during antral pressure wave periods.
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To determine whether this subjective observation is a general one, we
search for a statistical relationship between antral peristaltic wave
activity and pyloric resistance (measured by pressure) in the four
high-activity subjects. In Fig. 9 we show, for each subject, pairs of frequency distributions of pressures in the
pylorus during periods of propagating HPEs in the antrum and periods of
antral quiescence, designated as described in METHODS. Subjects 2, 5, and 7 display similar characteristics:
at the lowest pyloric pressures, within a few mmHg from
P*P when the resistance to transpyloric
flow is at a minimum, the fraction of samples is very much lower during
propagating antral HPEs than during quiescent periods in the antrum.
This drop in the fraction of pressure samples in the range
P*P to
P*P + 4 mmHg is roughly a factor of 2 and is statistically significant (P = 0.028). Thus the
probability of transpyloric flow for these three subjects is
significantly higher during antral quiescent periods than during antral
propagating pressure waves.
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The same trend is not observed with subject 6. This difference is a direct reflection of the difference in extent of the low-pressure gap that precedes the pyloric channel (Fig. 4B). Because the low-pressure gap is over twice as wide in subject 6 as in subjects 2, 5, and 7 (Table 2), the antral peristaltic pressure waves progress to only within ~3 cm of the pyloric channel before terminating. As a consequence, these distant peristaltic pressure waves had little influence on pyloric pressure variation for this subject.
The relationship between pyloric resistance and antral pressure
activity is analyzed further in Fig. 10,
where the level of pyloric resistance is correlated with the
advancement of antral contraction waves. Specifically, average pyloric
pressure for the periods when propagating HPEs pass each antral
pressure port is plotted in Fig. 10 as a function of the antral port
number. The antral ports are numbered A1-A8 from the most
distal to the most proximal, each port separated by 3.3 mm beginning
with port A1, which is 1 cm proximal to the pyloric port. The
average pressure in the pyloric port is plotted relative to
P*D. Figure 10 shows that pyloric
resistance increases as antral pressure waves move closer to the
pylorus. The increase in pyloric pressure with decreasing distance from
the pylorus is significant in subjects 2, 5, and 7 (P = 0.038). Consistent with Table 2, the advancing pressure
waves in subject 6 terminate much more proximally than in
subjects 2, 5, and 7. Figure 10 suggests that the
pyloric response to antral pressure waves may not begin until the
antral waves are 2-3 cm above the pylorus and that the peristaltic pressure waves in subject 6 terminate before a pyloric response is triggered.
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DISCUSSION |
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Gastric emptying is analyzed in this study as a series of local
transpyloric flow events that integrate to produce a reduction in
gastric volume of 130-460 ml over a 30-min period (Table 2). Time-local transpyloric flow events can be roughly classified in two
groups: flow associated with local increases in PA PD due to antrally propagating pressure waves and flow
associated with a common cavity pressure difference between the distal
antrum and the proximal duodenum in periods of quiescence between
antral HPEs. The first class of flow events is associated mechanically with a peristaltic pump mechanism of flow and the second class with a
pressure pump mechanism of transpyloric flow. Whereas propagating pressure waves originate from corresponding localized propagating contraction waves, as illustrated in Fig. 1, common cavity pressure changes can also arise from global tonic sources dispersed anywhere over the gastric wall.
On the other hand, flow can only occur in the presence of an open
pylorus. The sensitivity of flow to the degree of pyloric opening is
evident through a relevant fluid physics approximation for viscous flow
through constrictions (2, 11, 12), which indicates that the rate of
transpyloric flow at any instance in time is proportional to
(PA PD)/R, where R is
pyloric resistance at that time. R is given by
µ/D4, where D is the average diameter of
the pyloric channel and µ is the gastric fluid viscosity. Because the
R is proportional to 1/D4, there is great
sensitivity between the rate of transpyloric flow and pyloric diameter.
Consequently, our evaluations of peristaltic vs. pressure pump
contributions to gastric emptying center on correlations between
antroduodenal pressure history and changes in R measured
indirectly through pyloric pressure.
Gastric emptying follows from the relationships between the pressure forces, which move the gastric contents against frictional resistance, and the gastric wall motions and muscle tone, which generate those pressure forces. Measurement of pressure-geometry relationships associated with emptying requires concurrent manometry with imaging in the antropyloroduodenal region, where emptying is controlled and where resolution requirements are most severe. We combined three-dimensional MRI and high-resolution manometry to monitor pressure-geometry motor events in the antropyloroduodenal regions of seven subjects while simultaneously measuring changes in gastric volume over 15-min intervals during emptying of a nonnutrient liquid with intraduodenal nutrient infusion at 2 kcal/min.
The seven subjects differed in the nature of high-pressure activity in
the antrum: three subjects displayed little high-pressure activity, and
four subjects exhibited consistent propagating high-pressure antral
events. Consequently, the seven subjects separated neatly into "high
antral activity" and "low antral activity" groups quantified by AUC (AUCmax), frequency, and total duration of HPEs.
Interestingly, whereas AUCmax was 10 times higher in the
high-activity group, there was no significant difference in the rate of
gastric emptying. Indeed, the correlation between the rate of emptying
and antral pressure activity was 0.65, suggesting a tendency for
a lower rate of emptying with higher levels of antral contractile
activity (Table 2, Fig. 6). This observation was the first indication that antral pressure wave activity may not play the dominant role in
slowed gastric emptying.
A second indication was given by Fig. 7, which shows that average antral pressure during quiescent periods of antral activity (also P*A) remained unchanged during reductions in gastric volume from 130 to 460 ml over 30 min. If the stomach wall were a purely elastic structure, emptying would imply decreasing elastic wall tension and decreasing intragastric pressure until the internal and external pressures equalize. Figure 7, on the other hand, suggests that active muscle wall tone increased, on average, during gastric emptying. Furthermore, whereas active tone apparently increased with decreasing gastric volume in all subjects, there was much variability in antral high-pressure activity among subjects (Table 2, Fig. 5), suggesting that increases in active wall tone are independent of contractile activity within the antrum. Because transpyloric flow is driven by a pressure drop across an open pylorus, the maintenance of constant common cavity pressure levels in the presence of major reductions in gastric volume suggests a physiological response to the decrease in gastric volume so as to maintain transpyloric flow in the absence of antral contraction-wave activity during periods of pyloric opening.
Furthermore, we found also that average pyloric pressure during quiescent periods in the pyloric channel is insensitive to changes in gastric volume (Fig. 7B). Tougas et al. (19) found that increases and decreases in the pyloric pressure on the order of 2 mmHg relative to P*A appeared to be correlated with pyloric closure and opening, respectively. Thus a significant decrease in the average pyloric pressure during quiescence over the 30-min period might have suggested that gastric emptying was maintained by a continual increase in the duration of pyloric opening. By contrast, the insensitivity of pyloric and antral pressures during quiescent periods to reductions in gastric volume suggests a significant role for common cavity pressure difference in gastric emptying.
Further evidence that the pressure pump may be an important contributor to gastric emptying during intraduodenal nutrient infusion is given in Table 3, where we find that antral pressure activity in the three low-activity subjects (subjects 1, 3, and 4) is almost entirely quiescent with no evidence of antral propagating pressure waves. Surprisingly, there was no statistically significant difference in the average rate of gastric emptying between these three subjects and the four subjects that displayed high levels of gastric emptying (Fig. 5), suggesting that the emptying was primarily from common cavity pressure difference in the presence of an open pylorus and that antral peristaltic activity has the potential to impede emptying. For this to be the case, transpyloric flow must be slowed during antral peristaltic pressure events. This conclusion follows from Figs. 8-10.
Figure 8 suggests that the presence of antral contraction waves is correlated with high pyloric resistance; statistical evidence supporting this conjecture is given in Figs. 9 and 10. For antral peristaltic contractions to contribute significantly to gastric emptying, increases in peristalsis-induced pressure in the distal antrum should be correlated with low pyloric resistance. We find just the opposite, however. Figure 9 shows that pyloric pressure was significantly higher during antral propagating pressure events than during quiescent periods of antral pressure activity, implying that the pylorus has a higher probability to be closed during peristaltic activity in the antrum than during the quiescent periods between HPEs.
More significantly, Fig. 10 suggests an interaction between pyloric
resistance and the relative location of advancing peristaltic pressure
waves. Within a zone of influence, it appears that the closer the
peristaltic wave to the pylorus, the greater the probability of the
pylorus to be closed. The peristaltic waves in one high-activity subject (subject 6) appear to terminate outside this zone of
influence, so pyloric resistance is not influenced by the advancing
pressure wave (Fig. 10). Because PA PD
is unaffected by the propagating pressure waves in this subject,
peristalsis does not contribute significantly to emptying.
We are led to hypothesize, therefore, that when gastric emptying is sufficiently delayed by nutrient stimulation of the duodenum, antral peristaltic wave activity interacts with pyloric opening to increase pyloric resistance and impede transpyloric flow during local periods when the peristaltic events have the highest potential to contribute to gastric emptying. Furthermore, we hypothesize that this interaction occurs within a zone of influence that appears to be on the order of 2-3 cm from the pylorus.
The overall conclusion that gastric emptying of nutrient liquids occurs primarily during periods of quiescence in antral pressure activity and, by implication, in antral contractile activity is consistent with a subjective observation made by Brown et al. (Ref. 3, p. 435) in their visual examinations of ultrasound images during emptying of chicken broth and beans from the human stomach. More quantitative observation from ultrasound images during emptying by Pallotta et al. (14) concludes, consistent with this study, that transpyloric flow of a nutrient liquid meal occurred primarily during periods "not associated with occlusive antral or duodenal proximal contraction." However, they go on to suggest, inconsistent with Fig. 10, no coordination between pyloric closure and antral contraction. Clearly, additional study of the fundamental mechanics and underlying neurophysiology is warranted.
In summary, we conclude from this study that, during gastric emptying of liquids slowed by controlled duodenal nutrient infusion at 2 kcal/min, gastric emptying was dominated by pressure pump mechanics resulting from common cavity pressure differences between the distal antrum and the proximal duodenum. Whereas antral peristalsis was common in four of the seven subjects, the peristaltic pump mechanism of transport across the pyloric channel contributed only minimally to gastric emptying because of relatively refined physiological coordination between antral peristalsis and pyloric resistance. Indeed, these results suggest that the delay in gastric emptying induced by nutrient stimulation of the duodenum follows from a coordinated response in which antral contractile activity increases together with increases in periods of high pyloric resistance and that this coupling may be controlled by a physiological response within a zone of influence extending proximally from the pylorus.
It should be stressed that the protocol analyzed here is specific to gastric emptying slowed by controlled intraduodenal infusion of nutrients at 2 kcal/min. It would be of great interest to extend the analysis to a wider range of gastric emptying states and larger samples within the high- and low-activity groups.
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APPENDIX |
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Cumulative frequency distribution and PSP.
The antral port cumulative frequency distribution (CFD) of pressure is
shown in Fig. 11 for subject 5 (with pressure characteristics similar to Fig. 6A). The CFD is
defined as the fraction of pressure samples in the antral port below a
variable pressure P plotted against P relative to
P*A. Clearly, the CFD must equal 0 at P
below the lowest pressure (approximately
P*A), and the CFD must approach 1 as P
approaches the highest pressure in the data set. The shape of the curve
between 0 and 1, however, is due to the structure of the signal. Figure
6A displays intermittent spikes in pressure rising from a
low-level bed of pressure fluctuations. Consequently, as the threshold
P increases from the basal pressure (P = 0), it encounters the highest
density of pressure samples, and the CFD increases rapidly (curve
portion C in Fig. 11). However, the density of intermittent
spikes is much lower, so that as P increases from the lower-level
fluctuations to the higher-level intermittent spikes, the rate of
increase in the CFD slows dramatically (B in Fig. 11) and the
CFD approaches a plateau (A in Fig. 11) at the highest-level
spikes in pressure.
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ACKNOWLEDGEMENTS |
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We thank Dr. Karen Quigley for help with statistical analysis of the data.
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FOOTNOTES |
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This study was supported by the Janssen Research Foundation, Swiss National Science Foundation Grant 32-45982.95, and Janssen-Cilag.
This study was reported in abstract form (10); related abstracts are Refs. 5 and 9.
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. §1734 solely to indicate this fact.
1 Interestingly, Stemper and Cooke (18) used the same threshold for counting HPEs in the antrum purely on the basis of subjective observation.
Address for reprint requests and other correspondence: J. G. Brasseur, 205 Reber Bldg., Dept. of Mechanical Engineering, Pennsylvania State University, University Park, PA 16802 (E-mail: brasseur{at}jazz.me.psu.edu).
Received 10 February 1999; accepted in final form 18 November 1999.
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