Vol. 275, Issue 4, H1404-H1410, October 1998
Hemodynamics of gastric microcirculation in rats
János
Peti-Peterdi,
Gergely
Kovács,
Péter
Hamar, and
László
Rosivall
Institute of Pathophysiology, Semmelweis University Medical School,
Budapest H-1089, Hungary
 |
ABSTRACT |
Recently, we
described a novel preparation of rat stomach for vascular micropuncture
studies. The aim of the present study was to directly measure basic
microvascular parameters along the length of the gastric vasculature.
Blood vessels were identified, and intravascular pressure was measured
with a servo-null transducer, vessel dimensions with videometry, blood
flow with microspheres, and plasma colloid osmotic pressure with an
osmometer. When systemic arterial pressure was 100-110 mmHg,
intravascular pressures in small arteries, primary, secondary, and
tertiary submucosal arterioles, mucosal terminal arterioles, and muscle
arterioles were 77.8 ± 2.6, 74.6 ± 2.5, 54.1 ± 1.8, 34.4 ± 1.6, 32.4 ± 1.2, and 30.5 ± 1.4 (SE) mmHg, respectively.
Intravascular pressures in collecting veins, secondary and primary
submucosal venules, muscle venules, and small veins were 26.6 ± 1.1, 21.8 ± 1.6, 17.1 ± 0.8, 18.2 ± 0.9, and 14.4 ± 0.6 mmHg, respectively. Capillary pressure in the mucosa (28 mmHg), as
estimated by interpolation between terminal arteriole and collecting
venule pressures, was significantly higher than in the muscle layer
(23.6 ± 1.4 mmHg). A total of 155 vessels from 25 animals were
sampled. Relative blood flows were 16 ± 3% in the muscle and 84 ± 3% in the mucosa-submucosa. Analysis of filtration forces in
these two different capillary beds suggests that gastric mucosal
capillaries are primarily a filtering network, whereas muscle
capillaries are in fluid balance. Calculated resistance ratios indicate
low precapillary but relatively high postcapillary vascular resistance
in the gastric mucosa.
microvascular pressures; gastric vasculature; blood flow
distribution; vascular resistance; transcapillary fluid exchange
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INTRODUCTION |
INTRAVASCULAR PRESSURES have been measured using
micropuncture techniques in several organs, including the small
intestine (13); however, direct information on the gastric circulation is lacking. Capillary hydrostatic pressures and other basic
microcirculatory factors governing transcapillary fluid exchange in the
stomach have been calculated indirectly or estimated from other
measured parameters of the Starling equation (15, 16). These
estimations, however, were speculative and based on data obtained with
inherently limited methods. Recently, we developed an in vivo
micropuncture method to measure intravascular pressures of various
microvessels in the muscle and submucosal and mucosal layers of the
gastric wall (29). This technique provides a means to obtain direct measurements of gastric microvascular parameters.
Previous studies have found significant regional differences in
capillary pressure and net transcapillary fluid movement between the
three major regions of the small intestine (13, 14), i.e., mesentery,
intestinal muscle, and mucosal layers. This finding implies that
microvascular regions in the gastrointestinal tract may continuously
filter (mesentery) or absorb (mucosa), whereas those in other regions
(muscle) may be in fluid balance. Because the stomach is a secretory
organ, further variations in capillary pressures could be found.
Furthermore, it has been well accepted that the intact mucosal
microcirculation is an essential factor in the ability of the gastric
mucosa to maintain its integrity against various aggressive factors
(19, 31, 37). Therefore, exact knowledge of gastric microcirculatory
and transcapillary fluid exchange parameters may also have importance
in understanding the mechanisms of mucosal protection.
The purpose of this study was to determine the profile of intravascular
pressures along the length of the gastric vasculature. The intramural
blood flow distribution between gastric muscle and submucosal-mucosal
layers was also measured so that precapillary-to-postcapillary resistance ratios could be calculated. Net transcapillary fluid movement across the muscle and mucosal microcirculation was also estimated, thereby providing an overall estimate of the Starling forces
that occur within various regions of the stomach.
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METHODS |
The methods used to prepare the submucosal and deep mucosal layers of
the gastric muscle for micropuncture studies are described briefly
below. Details of this technique have been described in a recent report
(29).
Animal Preparation
Male Wistar rats, weighing ~200 g, were fasted overnight with free
access to water. Rats were anesthetized with thiobutabarbital sodium
(Inactin-BYK, 120 mg/kg body wt ip) and placed on a micropuncture table, and body temperature was maintained at 37 ± 0.5°C by
means of a heating pad controlled by a rectal thermistor probe. A
tracheotomy was performed, and the trachea was intubated to facilitate
spontaneous breathing. Systemic arterial blood pressure was monitored
continuously through a PE-50 catheter placed in the left femoral artery
and connected to a Statham electromanometer (model P23). A long,
heparinized catheter (PE-50) was inserted into the left femoral vein,
and Ringer solution (1.5 ml · h
1 · 100 g body wt1) was infused
throughout the surgical preparation and experimental periods; this
preparation was also used to measure systemic venous pressure.
Tissue Preparation
The abdomen was opened via a 5-cm midline incision, the stomach was
gently exteriorized, and surrounding gastric ligaments were cut. The
exposed stomach was continuously bathed in warmed Ringer solution to
avoid desiccation and irreversible cessation of blood flow in the
superficial blood vessels. The animal was positioned on its right side
on the micropuncture table, and the stomach was placed in a gastric
chamber. The heating pad and continuous superfusion (1 ml/min) of warm
Ringer solution kept the vascularly intact and innervated stomach in a
constant environment with high humidity and a temperature of 37 ± 1°C. To stabilize the preparation with the posterior wall facing
up, four small pins were inserted into the chamber wall through the
esophagus, antrum, forestomach, and corpus (see diagram of gastric
chamber and instrument setup in Ref. 29). However, to avoid
respiration-induced gastric movements and changes in macrovascular
parameters (e.g., venous pressure elevation) due to stretch, the
esophagus was not tightly fixed. Care was taken to prevent compression
or excessive manipulation of the left gastric artery, vein, and nerves
to the stomach.
Vessels in different layers of the gastric wall were approached from
the serosal side. A very light rubber ring was mounted over the gastric
surface to serve as a reservoir for a film of fluid that was needed for
the micropuncture technique (see diagram of gastric chamber and
instrument setup in Ref. 29). The narrow gap between the rubber ring
and the preparation was sealed with agar gel. The area inside the ring
functioned as a working window, where the tip of the superfusion system
was located. The working window consisted of two parts, the
seromuscular and submucosal areas, each supplied by different small
arteries. The seromuscular area served for micropuncture measurements
in vessels of the muscle layer. To approach the submucosal and deep
mucosal vasculature, a 1-cm-diameter piece of seromuscular tissue on
the posterior wall of the corpus was removed by careful dissection from
an area free of large vessels. In a small area of this submucosal
preparation, we totally removed the submucosal connective tissue and
the superficial part of the muscularis mucosae. In this way, the
microvessels in the basal mucosa also became accessible through the
remaining thin muscularis mucosae. After completion of the experimental setup, the tissue was allowed to equilibrate for 1 h before any experiments were attempted. Vascular reactivity was well preserved, and
the minimal exteriorization procedure did not have significant adverse
effects on the vessels under study, as have been assessed and tested in
our recent report (29).
Measuring Techniques
The preparation, illuminated with an fiber-optic illuminator (Intralux
4000-1, Volpi), was visualized using a zoom stereomicroscope (model M8,
Wild). Pressures were measured in microvessels with a servo-null
transducer (model 4A, IPM) (20, 21, 36). A Leitz micromanipulator was
used to insert sharpened micropipettes (0.5-2 µm) into selected
vessels. Each micropipette was calibrated over the range 0-200
mmHg in a calibration chamber using a manometer. Microvascular pressure
and systemic arterial blood pressure were recorded simultaneously on a
recorder (model OH-814/1, Radelkis). Microvessel images were viewed
through the microscope with a television camera (model SSC-M370CE,
Sony), continuously displayed on a television monitor (model PVM-145E,
Sony), and recorded on a videocassette recorder (model SLV815VP, Sony).
Vessel dimensions were determined using the microscope eyepiece
micrometer and measured in video recordings displayed on the television
screen with a caliper.
In a separate series of experiments, we studied intramural blood flow
distribution between gastric muscle and submucosal-mucosal layers using
the Dye-Trak microsphere technique (3, 24). All reagents and disposable
supplies were obtained from Fisher Scientific. Approximately
106 red microspheres, 15 µm
diameter (Triton Technology, San Diego, CA) and suspended in 1 ml of
saline containing 0.05% Tween 80, were injected into the ascending
aorta over a 10-s period through a catheter placed into the right
carotid artery. At 5 s before microsphere injection, a 30-s microsphere
reference sample was collected by free-flow technique into a
heparin-coated glass tube from the distal abdominal aorta through a
cannula inserted into the left femoral artery. Two minutes after
injection, the rat was killed, and the stomach was removed and divided
into muscle and submucosal-mucosal layers by manual dissection. Each
tissue and reference blood sample was weighed and then digested in
glass tubes with 7 ml of 4 M KOH. The volume of the reference blood sample was calculated by weight according to the specific gravity (30).
The digested tissue solution was filtered through a polyester filter
with a pore size of 10 µm (Triton Technology) in a glass microanalysis filter holder (model 09-735G, Fisher Scientific). After
filtration, microspheres were quantified by their dye content recovered
by addition of 300 µl of dimethylformamide. The photometric absorption of each dye solution was determined using a
spectrophotometer (model 8452A, Hewlett-Packard), and blood flow to
each layer was calculated from the following relationship
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where
B is blood
flow
(ml · min1 · 100 g1),
AUL is absorbance unit per layer
sample, WR is reference blood flow rate (ml/min), AUR is absorbance unit per
reference blood sample, and LW is layer weight (g). The relative blood
flow of gastric muscle or submucosal-mucosal layers was calculated as
follows
where
R is the percent ratio of total gastric blood flow and
AUmus and
AUmuc are the absorbance units of
muscle and submucosal-mucosal layer samples, respectively.
Plasma colloid osmotic pressure was measured from plasma samples using
a colloid osmometer as described by Aukland and Johnsen (4).
Data were analyzed with a statistical software package (SigmaStat for
Windows, Jandel Scientific). ANOVA was applied for intergroup comparison of intravascular pressure data from different vessel types.
Values are means ± SE. P < 0.05 was considered significant.
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RESULTS |
Vessel Identification and Description of Vascular Architecture
Microvessels in rat gastric wall were identified (Fig.
1) according to branching hierarchy and
relative dimensions or with a descriptive classification similar to the
system proposed by Wiedeman (35) and applied to the small intestine by
Gore and Bohlen (13).
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Fig. 1.
Schematic representation of microvasculature in gastric wall. Blood
vessels were identified numerically according to their branching order
and vascular hierarchy: small artery (SA), submucosal primary (SMA1),
secondary (SMA2), and tertiary (SMA3) arterioles, mucosal terminal
arteriole (MTA), collecting venule (CV), submucosal secondary (SMV2)
and primary (SMV1) venules, muscle arteriole (MA), capillary (MC), and
venule (MV), and submucosal small vein (SV). Common input and output of
muscle and mucosal circulations are SMA1 and SMV1.
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The posterior branch of the left gastric artery, a major branch of the
celiac axis, gives rise to a series of long vessels supplying the
posterior corpus. These vessels pierce the external muscle layers at
the lesser curvature near the cardia and run under the muscle coat in
the superficial submucosa radially toward the greater curvature. The
diameter of these small arteries (SA) is 89.1 ± 2.1 µm.
Submucosal and deeper mucosal vasculature.
Through the process of anastomoses, small arteries form the main
submucosal arterioarterial anastomotic plexus or primary arcade of
submucosal arterioles (SMA1) and average 75.5 ± 1.8 µm in
diameter. In turn, these vessels form smaller and smaller branches,
which interconnect with each other and the parent vessels forming a
secondary and a tertiary arcade of submucosal arterioles (SMA2 and
SMA3, 42.3 ± 1.6 and 24.4 ± 0.8 µm, respectively). These arcades form a very extensive, interconnecting arterial network in the
submucosa. The tertiary arcade gives rise to small mucosal terminal
arterioles (MTA, 15.5 ± 0.7 µm), which run perpendicularly through the muscularis mucosae and, on entering the mucosa, divide into
the hexagonal mucosal capillary plexus. Collecting veins (CV) run
perpendicularly through the mucosa and, on cross section, appear as
dark round dots that are 36.4 ± 1.1 µm diameter. Within the
deeper mucosa they drain into the venous anastomosis, which, on
entering the muscularis mucosae, gives rise to the secondary arcade of
submucosal venules (SMV2). This observation of the mucosal venous
architecture is somewhat different from previous descriptions (12, 17,
32); however, the existence of a deep mucosal venous anastomosis is
further supported by a recent study (27). Interestingly, collecting
venules were larger in diameter (36.4 ± 1.1 µm) than the deeper
mucosal venous anastomosis (31.5 ± 1.3 µm) or the
initial part of SMV2. SMV2 are larger than their respective arteries
(55.8 ± 1.3 µm) and interconnected in a similar manner. SMV2
enter the primary arcade of submucosal venules (SMV1, 87.5 ± 1.6 µm), which follow the same course as the primary
arterioles and return blood to the small veins (SV, 99.1 ± 1.8 µm). These SV run parallel with SA, penetrate the
external muscle layers, and leave the superficial submucosa.
Muscle vasculature.
SA or initial parts of SMA1 give rise to ascending muscle arterioles,
which supply muscle arterioles (MA, 16.6 ± 0.8 µm diameter) in
the circular and longitudinal muscle layers. These arterioles run
perpendicularly to the muscle fibers and divide into the longitudinal and circular muscle capillaries (MC, 4.8 ± 0.4 µm), which run parallel to the muscle fibers. Capillaries end in muscle venules (MV,
23.2 ± 0.9 µm), which form descending venules through both muscle
layers and return blood to the SMV1 or SV before leaving the submucosa.
Figure 2 shows an ink-stained preparation
of gastric vasculature and the various branches of the gastric
circulation.
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Fig. 2.
Micrograph of gastric microvasculature injected with india ink. See
Fig. 1 legend for vessel identification.
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Intravascular Pressure Distribution
Microvascular pressure was measured for up to 5 h with no signs of
deterioration of the tissue as judged by the absence of leukocytes
sticking and rolling along the walls of venules or progressive
dilatation of arterioles and large-amplitude vasomotion. In most
animals, spontaneous gastric muscle contractions and respiratory movements were small enough to allow micropuncture measurements. The
results of microvascular pressure and dimension measurements are
summarized in Figure 3. A total of 155 vessels from 25 animals were sampled. Systemic arterial and venous
blood pressure averaged 108 ± 2 and 7 ± 0.5 mmHg, respectively.
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Fig. 3.
Intravascular pressure distribution in gastric vasculature. Data were
recorded from muscle ( ) and mucosal blood vessels ( ) at systemic
arterial pressures of 100-110 mmHg. See Fig. 1 legend for vessel
identification. Values are means ± SE;
n, number of vessels. A total of 155 vessels from 25 animals were sampled.
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Submucosal and deeper mucosal vasculature.
Pressures in submucosal SA averaged 77.8 ± 2.6 mmHg. Only slightly
lower pressures were measured in SMA1 (74.6 ± 2.5 mmHg), which is
not surprising, since SMA1 are shunt vessels between adjacent small
arteries. About one-half of the systemic pressure was found in SMA2
(54.1 ± 1.8 mmHg). Pressures in SMA3 averaged 34.4 ± 1.6 mmHg,
significantly less than in SMA2 but similar to the pressures in MTA
(32.4 ± 1.2 mmHg). Pressures in CV, SMV2, SMV1, and SV were 26.6 ± 1.1, 21.8 ± 1.6, 17.1 ± 0.8, and 14.4 ± 0.6 mmHg,
respectively. Mucosal capillary pressure was estimated from input (MTA)
and output (CV) pressures of the mucosal capillary network by
calculating the mean and resulted in 28 mmHg. The validity of this
estimation was tested using intravascular pressure data obtained from
the muscle microvasculature. Because the difference between calculated
(24.3 mmHg) and measured (23.6 ± 1.4 mmHg) MC pressure was not
significant, the value of 28 mmHg for mucosal capillary pressure was
accepted.
Muscle vasculature.
Pressures were not measured in ascending arterioles or descending
venules because of technical difficulties. However, the greatest
pressure drop was apparent across these arterioles, since the MA
pressure was 30.5 ± 1.4 mmHg, less than one-half of SMA1 pressure.
Microvascular pressure further decreased to 23.6 ± 1.4 mmHg in the
MC and to 18.2 ± 0.9 mmHg in MV. Figure
4 compares precapillary, capillary, and
postcapillary hydrostatic pressures from muscle and mucosal layers.
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Fig. 4.
Precapillary, capillary, and postcapillary hydrostatic pressures in
muscle () and mucosal regions () of gastric vasculature. See Fig.
1 legend for vessel identification. Values are means ± SE;
n, number of vessels.
* P < 0.05 compared with
corresponding segment in muscular circulation (by ANOVA).
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Intramural Blood Flow Distribution
Absolute and relative blood flows to gastric muscle and mucosal layers
were measured in 11 additional animals. Because the submucosal and
mucosal microvasculatures are coupled and cannot be separated by manual
dissection, we report mucosal and submucosal flows as a single value.
However, the scarcity of submucosal capillaries would suggest that
submucosal flow is only a small fraction of total gastric blood flow.
Absolute flows to the muscle and submucosal-mucosal regions averaged
70.4 ± 22.3 and 120.8 ± 18.8 ml · min1 · 100 g1, respectively. From
calculation of the relative blood flow distribution, the gastric muscle
layer received 16 ± 3% and the submucosa-mucosa 84 ± 3% of total gastric blood flow. These results are comparable to those
from other studies (3, 5, 11).
Plasma colloid osmotic pressure was measured from 27 samples of 25 animals; it averaged 18.9 ± 1.7 mmHg and is within the normal range
(38).
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DISCUSSION |
Microvascular pressures have been measured in different organs,
including the small intestine (13), but studies from gastric microvessels are lacking. Previously, gastric mucosal hydrostatic capillary pressure has been estimated from the balance of Starling forces, resulting in a value of 10.6 mmHg (15, 16). In contrast, we
found that mean capillary pressure in different regions of the gastric
vasculature ranges from 20 to 30 mmHg, values that are significantly
higher than previously calculated. This discrepancy may be explained
partly by inherent limitations in the methods used in previous
calculations. For example, the rate of lymph flow was used as an
estimate of net capillary filtration rate (6). However, lymph flow may
not accurately reflect capillary filtration rate if significant
transepithelial fluid secretion or absorption occurred during the
period in which lymph flow was measured. In secreting organs, such as
the stomach, capillary filtration rate could be significantly
underestimated by lymph flow, since a proportion of the capillary
filtrate would be removed from the interstitial spaces via the
transporting epithelia rather than the lymphatics. Furthermore,
previous calculations of Starling forces used a value of interstitial
fluid pressure measured with microcapsules implanted in the gastric
submucosa (1). Because this layer of the gastric wall has only a few
nutritive capillaries compared with the dense mucosal capillary system,
tissue factors governing transcapillary fluid exchange in the submucosa
are most probably different from those of the mucosa.
Another factor that could significantly modify microcirculatory
hydrostatic pressures is muscle activity. Many studies have shown that
the motor activity of the intestine can affect blood flow (8-11,
18, 23, 33). In these experiments a large increase in intramural
pressure produced by distension or prolonged tonic contraction was
accompanied by an increased local vascular resistance. Changes in blood
flow have been explained as a result of passive changes in vessel
caliber due to changes in vascular transmural pressure subsequent to
alterations in motility. In our preparation, muscle contractions can
also increase passive resistance of blood vessels. SA, SV, and
ascending arterioles and descending venules run perpendicularly to the
outer muscle layers. Furthermore, MTA and SMV2 penetrate the muscularis
mucosae in a similar manner. Ample evidence has been presented (1) that
the basal tone of gastric muscles and peristaltic waves also increase
the interstitial fluid pressure. In comparison to earlier methods (7,
17, 32), in which gastric or intestinal wall and muscle were transected and the mucosa was exteriorized, in our preparation the whole stomach
was fixed in the gastric chamber without surgery. Thus the effect of
tonic muscle contraction on vascular and interstitial hydrostatic
pressure was included in our experimental results. However, because of
this lack of exposure, we could not measure mucosal interstitial fluid
pressure by direct micropuncture. On the other hand, we could not
document the possible effect of peristalsis on intravascular pressure
(i.e., oscillation in pressure), because, as a result of contractions,
small vessels could be penetrated for a relatively short period
(15-20 s). Also, oxygen is a potent vasoconstrictor, and high
oxygen superfusates (such as those equilibrated with room air) have
long been known to cause arteriolar constriction and decreased blood
flow in exteriorized tissues (22, 25, 34). Most intravital microscopy
studies use a superfusate equilibrated with a 0 or 5% oxygen gas
mixture to prevent abnormally high oxygen levels in the tissue. This
ensures that tissue oxygenation is achieved solely by blood oxygen
delivery (as it is in situ) and that the superfusate is not a source of
additional oxygen. Therefore, our high-oxygen superfusate could have
had some effect on arteriolar tone and the microvascular pressure
profile, although we did not observe any indication of such
vasoconstriction.
Digestive juices are secreted each day by the salivary glands, stomach,
pancreas, liver, and small intestine. Although emphasis has been placed
on the importance of the epithelium in secretory transport of fluid in
digestive organs, the role of the microcirculation in transporting
fluid to and from the epithelium has received relatively little
attention. We found that mean capillary pressure in the gastric mucosa
was 28 mmHg, whereas plasma oncotic pressure was 18.9 ± 1.7 mmHg.
With the use of these values together with additional data from other
studies, it is possible to estimate filtration forces in the gastric
mucosal microcirculation. If we consider the values of gastric lymph
protein concentration and osmotic reflection coefficient (28) and
assume a small positive value for the interstitial fluid pressure (1),
there is a 10- to 15-mmHg net driving force for transcapillary
filtration. A total safety factor against edema formation (increased
lymph flow, interstitial fluid pressure, transcapillary oncotic
pressure gradient) has been described for intestinal mucosa and ranges
from 12 to 15 mmHg (26). Thus, from this information, gastric mucosal
interstitium may be well hydrated and close to fluid imbalance under
resting conditions. These conditions may thereby supply the fluid
necessary for active epithelial secretion. Further increments in
mucosal capillary pressure in excess of 15 mmHg, which may happen
during peristaltic muscle contractions, particularly those of the
muscularis mucosae, may lead to enhanced passive gastric secretion.
Evidence has been shown that increases in interstitial fluid pressure
are associated with alkaline fluid secretion across the gastric mucosa (2). Flow of interstitial fluid across the gastric mucosa (so-called gastric filtration) has been observed under a variety of experimental conditions, e.g., elevation of arterial and venous pressure and intra-arterial infusion of ACh, which leads to increased capillary filtration and strong muscular activity (2). Thus one can further speculate that, during peristaltic muscle contractions, high mucosal capillary pressure results in elevated interstitial hydrostatic pressure and an enhanced alkaline fluid secretion, and this may play an
important role in protection against luminal acidity.
We found that capillary pressure in the gastric muscle layer was
significantly less (23.6 ± 1.4 mmHg) than the calculated mean
capillary pressure in the mucosa (28 mmHg) at normal systemic arterial
pressures (100-110 mmHg; Fig. 4). This suggests that the Starling
forces across the muscle microcirculation may be closer to equilibrium.
This idea is further supported by the anatomic difference between the
two capillary beds; i.e., mucosal capillaries are of the fenestrated
type, whereas those in the muscularis are of the less permeable
continuous type. Our findings are consistent with direct pressure
measurements by Gore and Bohlen (13, 14) from the rat small intestine,
which showed regional differences in capillary hydrostatic pressure
between muscle and mucosal layers. They suggested that mesenteric
capillaries are primarily a filtering network; intestinal muscle
capillaries are normally in fluid balance, whereas, at rest, intestinal
mucosal capillaries are primarily absorptive. These findings imply that
there are regional differences in transcapillary fluid exchange in the
gastrointestinal tract, whereas the whole organ is essentially in fluid
balance.
The gastric vasculature is composed of two structurally different
microvascular beds, which are connected in parallel at the level of the
submucosa. Microsphere measurements indicated that, under resting
conditions, the mucosa-submucosa receives 84 ± 3% of the total
gastric blood flow and the muscularis 16 ± 3%. These findings are
consistent with previous work using similar techniques (3, 5, 11).
Differences in intravascular pressure distribution between the muscle
and the mucosal region may be explained in terms of differences in
vascular morphology, architecture, and relative resistances in the two
regions. In Fig. 3 the arterial pressure drop down to the precapillary
arterioles was almost identical; pressure was 32.4 ± 1.2 mmHg in
MTA and 30.5 ± 1.4 mmHg in MA (P = NS). However, there was a significant difference in capillary pressures: 23.6 ± 1.4 mmHg average MC pressure and 28 mmHg
calculated mucosal capillary pressure. We suspect that the difference
in mucosal and MC pressure profiles was due to a significant
postcapillary venous resistance in the mucosa, because a large pressure
drop was observed from CV (26.6 ± 1.1 mmHg) through the SMV2 (21.8 ± 1.6 mmHg) and into the SMV1 (17.1 ± 0.8 mmHg). We found that CV, on the mucosal side of muscularis mucosae, were larger in diameter
(36.4 ± 1.1 µm) than the following deeper mucosal venous anastomosis (31.5 ± 1.3 µm) or initial part of SMV2, on the
submucosal side of muscularis mucosae. Semiquantitative evidence for
our argument can be obtained by calculating simple resistance ratios from the pressure and relative flow data.
Assume that gastric muscle and mucosal vasculatures can be represented
by two simple parallel circuits with a common input at the level of the
SMA1 and a common output at the level of the SMV1. As we described, the
drop in arterial pressure down to the MA and MTA was identical.
Therefore, intravascular pressures in these arterioles were considered
the input values. It is a simple matter to calculate resistance ratios
in this model using relative flow data from the microsphere experiments
and intravascular pressure data from Fig. 3. Four different resistance
ratios were calculated as follows
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(1)
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(2)
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(3)
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(4)
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where
Ra and
Rv are the
precapillary and postcapillary resistances in the muscle or mucosal
vasculature as indicated,
mus/t and
muc/t
represent the fractional blood flow through the muscle and mucosal
layer, respectively, and PMA,
PMTA,
PSMV1, and
Pc denote the average pressures in
MA, MTA, and SMV1 and corresponding capillaries, respectively.
Substituting the appropriate values into Eqs.
1-4, we find that
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(1a)
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(2a)
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(3a)
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(4a)
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The
large values of precapillary
(Ra mus/Ra muc = 8.23) and postcapillary
(Rv mus/Rv muc = 3.13) resistance ratios of muscle to mucosal circulations indicate
low mucosal vascular resistances. This would be expected, because there
are approximately five times as many capillaries in the mucosal
circulation as in the muscle vasculature. [If we assume that the
microspheres used to measure the relative blood flows were distributed
in direct proportion to the number of parallel channels in each tissue
region,
(muc/t)/(mus/t) = 0.84/0.16 
5.] In turn, the precapillary-to-postcapillary
resistance ratio in the muscle vasculature
(Ra mus/Rv mus = 1.06) indicates a fairly large equal precapillary and postcapillary
resistance in the muscle layer. However, the low mucosal
precapillary-to-postcapillary resistance ratio
(Ra muc/Rv muc = 0.40) suggests that mucosal venules offer high resistance to flow.
Therefore, when considered relative to the low mucosal vascular
resistances, mucosal venules may be an important determinant of the
high mucosal capillary pressure, besides the low precapillary
resistance. The relatively high gastric mucosal postcapillary venous
resistance is somewhat unique, since very low venular resistances were
described in other parts of the intestine (13, 15, 16).
In summary, the present investigation indicates that gastric capillary
hydrostatic pressure in the mucosal microcirculation is significantly
higher than capillary pressure in the muscle vasculature. Morphological
findings and the calculated vascular resistances indicate that the
regional difference in capillary pressures may be due to low
precapillary, but relatively high postcapillary, resistance in the
mucosal microcirculation. Analysis of filtration forces suggests that
fluid balance is not maintained in the gastric mucosal
microcirculation, which appears to be primarily a filtering
network. This conclusion is consistent with the secretory function of
this organ.
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ACKNOWLEDGEMENTS |
The authors are grateful to Dr. P. Darwin Bell for critical reading
and revision of the manuscript and to S. Adamkó, M. Godó, and G. Nagy for technical assistance.
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FOOTNOTES |
This work was supported by Hungarian Ministry of Welfare Grant
ETT-02290/93, Hungarian Research Foundation Grant OTKA T-017414, and
the Semmelweis University Medical School.
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.
Address for reprint requests: L.R. Rosivall, Institute of
Pathophysiology, Semmelweis University Medical School, Budapest H-1089,
Nagyvárad tér 4, Hungary.
Received 23 March 1998; accepted in final form 25 June 1998.
| |
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