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ABSTRACT

LOCAL INTESTINAL HYPEREMIA DUE
TO LUMINAL PRESENCE OF FOOD
OF DIFFERENT CONCENTRATIONS

BY

Peter R. Kvietys

It has been hypothesized that the postprandial
intestinal hyperemia may be restricted to that portion of
the intestine directly in contact with food. The purpose
of the present study was twofold: l) to further assess the
hypothesis that the intestinal hyperemia produced by the
luminal presence of digested food is a local phenomenon and
2) to examine the effects of the concentration (and/or
tonicity) of the food in the lumen on the local hyperemia
and intestinal motility. To meet this purpose two different
surgical preparations of anesthetized dogs were used.

In one preparation the blood flows through the
superior mesenteric artery (SMA) and an isolated jejunal
segment were simultaneously measured by electromagnetic
flowmeter and timed collections of venous outflow respec-
tively during two experimental procedures: 1) Infusion of
undiluted digested dog food through the lumen of the
duodenal-jejunal portion of the intestine at 4 cc/min for

one hour, while the isolated jejunal segment had no contact

Peter R. Kvietys

with food, and 2) Intraluminal placement of undiluted
digested dog food into the isolated jejunal segment for
fifteen minutes while the duodenalejejunal portion of the
intestine was left intact.

During the perfusion of the duodenal-jejunal
portion of the intestine with food, SMA flow increased
while the venous outflow from the isolated jejunal segment
did not change. The intraluminal placement of digested
food into the jejunal segment, on the other hand, increased
the venous outflow of the segment but did not alter the
SMA flow.

In another preparation, the venous outflows and
luminal pressures (basal and phasic) of two naturally per-
fused in gitu jejunal segments were simultaneously measured
while undiluted or diluted (1:2, 1:4, or 1:9 with distilled
water) digested food was placed in the lumen of one segment
and normal saline in the other segment. The segment con-
taining normal saline served as a control for the segment
containing food. As an indicator of the osmolality of the
digested food in the lumen, the osmolality of the venous
outflow and changes in the volume of the placed food or
normal saline were also measured. Furthermore, the four
digested food mixtures were centrifuged and the osmolali-

ties of the supernatants were determined in_vitro.

Peter R. Kvietys

The luminal placement of undiluted digested food,
1:2, 1:4, or 1:9 food increased the venous outflow of the
segment containing food, but did not affect the venous out-
flow of the control segment. As compared to the changes in
the venous outflow occurring in the control segment, the
magnitude of the increased venous outflow from the segment
containing food was similar whether undiluted or any of the
diluted foods was present in the lumen. Luminal presence
of undiluted food increased the venous osmolality, phasic
and basal luminal pressures and the volume of the placed
food. Luminal presence of the 1:2, 1:4, or 1:9 diluted
food did not alter venous osmolality or luminal pressure;
the volume of the placed food, however, was decreased. The
decrease in the placed volume of the 1:2, or 1:4 diluted
food was comparable to the decrease in the placed volume
of normal saline. The decrease in the placed volume of the
1:9 diluted food was greater than the decrease in the placed
volume of normal saline. £2.2iEE2 the osmolalities of the
supernatants of centrifuged undiluted, 1:2 diluted, 1:4
diluted and 1:9 diluted foods were approximately 1100, 331,
203, and 108 mOsm/kg respectively. 12.2312 the direction
and magnitude of the changes in the placed volumes and
venous osmolality indicate that, in the lumen, undiluted

food is hypertonic, 1:2 diluted food is nearly isotonic,

LOCAL INTESTINAL HYPEREMIA DUE
TO LUMINAL PRESENCE OF FOOD

OF DIFFERENT CONCENTRATIONS

BY

Peter R. Kvietys

A THESIS

Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of

MASTER OF SCIENCE

Department of Physiology

1975

To my parents and my wife, Kathryn

ii

AC KNOWLEDGMENTS

The author wishes to thank his advisor Dr. C. C. Chou
for his patience and guidance during the course of this study
and the preparation of this thesis. A special thanks is ex-
tended to Dr. J. M. Dabney and Dr. R. Pittman for their review
of this thesis and suggestions for its improvement, as well as,
for their service on the guidance committee.

The author would also like to thank Mrs. Jodi Johnston
for her work on the chemical analyses necessary for this study,
and my wife Kathryn for her patience in typing the rough drafts

of this thesis.

iii

TABLE OF CONTENTS

LIST OF TABLES AND FIGURES . . . . . . . . . . . .

Chapter
I 0 INTRODUCTION 0 O O O I 0 O O O 0 O O O O 0
II. LITERATURE REVIEW . . . . . . . . . . . . .

Feeding and Circulatory Adjustments . . .
“Studies Prior to 1966" . . . . . . . .
"Studies After 1966" . . . . . . . . .

Studies on Isolated Intestinal Segments .

III 0 METHODS O O I O O O O O O O O O 0 O O O O 0
Preparation of the Digested Dog Food
Mixtures and Their Supernatants . . . .
Control Solutions . . . . . . . . . . . .
Surgical and Experimental Procedures . .
(A) Preparation I . . . . . . . . . . .
(B) Preparation II . . . . . . . . .
Expression of Data and Statistical Methods
IV. RESULTS 0 O O O I O O O O O O O O I O O O O
V. DISCUSSION O O O O O O O O O O O O O O O 0
VI. SUMMARY AND CONCLUSIONS . . . . . . . . . .

BIBLIOGMPHY O O O O O O O O O O O O O O O O O O 0

iv

14
20

36
37
38
38
38
42
45
48
62
76

81

LIST OF TABLES AND FIGURES

Tables Page

1. Average venous outflow (m1/min/100 gm) before,
during and after luminal placement of un-
diluted (1:0) or diluted (1:2, 1:4, or 1:9)
digested food in one and normal saline
(I-NaCl) in the other segment of the double
segment preparation . . . . . . . . . . . . . . 52

2. Average vascular resistance (mm Hg/ml/min/lOO gm)
before, during and after luminal placement
of undiluted (1:0) or diluted (1:2, 1:4, or
1:9) digested food in one and normal saline
(I-NaCl) in the other segment of the double
segment preparation . . . . . . . . . . . . . . 53

3. Percent change from precontrol value of blood
flow (Flow) and vascular resistance (Res.)
while one of the four digested food mixtures
was in the lumen of the experimental segment
(E) and normal saline in the control segment
(C) (Mean : S.E.) . . . . . . . . . . . . . . . 56

4. Basal and phasic luminal pressures (mm Hg) of
two jejunal segments while one of the
digested food mixtures or normal saline
(I-NaCl) was in the lumen (Mean : S.E.) . . . . 58

5. The osmolality of the venous outflow (Osm.,
mOsm/kg) and gains (+) or losses (-) in
the placed volume (Vol., ml.) while either
one of the digested food mixtures or normal
saline (I-NaCl) was in the lumen for a 15
minute period (Mean : S.E.) . . . . . . . . . . 60

6. The osmolalities (mOsm/kg) of supernatants of
centrifuged (19,250 x G) undiluted or
diluted (1:2, 1:4 or 1:9 with distilled
water) digested food . . . . . . . . . . . . . 61

Figure Page

1. TOP: Blood flow, as percent of control,
of the superior mesenteric artery (SMA)
and the isolated jejunal segment during
infusion of digested food into the duo-
denum at 4 cc/min.

BOTTOM: Blood flow, as percent of the
control, of the superior mesenteric
artery (SMA) and the isolated jejunal
segment prior to and after luminal place-
ment of digested food into the jejunal
segment . . . . . . . . . . . . . . . . . . . . 50

vi

CHAPTER I

INTRODUCTION

Virtually all of the existing evidence suggest that
the blood flow to the Splanchnic viscera increases after a
meal in man (4, 10), primates (54), dogs (7, 8, 29, 30, 36,
37, 54-56), and rats (43). Only one study indicates that
the superior mesenteric artery blood flow remains unchanged
after a meal in dogs (45).

Prior to the mid 19608, it was generally accepted
that the postprandial splanchnic hyperemia was a result of
an increase in the cardiac output. This concept was based
primarily on indirect measurements of the postprandial
cardiac output and regional blood flow in man, dogs, and
rats. Measurements of cardiac output using gas equilibrium,
dye dilution, or balistocardiogram methods indicated that
the cardiac output increases by 25-45 percent during the
digestion of a meal (3, 24, 26, 31, 33, 42-44, 50). Measure-
ments of regional blood flow using plethysmographic, thermo—
stromuhr, and K42 distribution methods indicated that blood
flow to the extremities, heart, kidneys, and brain also

increases after meals (1, 28, 37, 43).

Since the mid 19605, the above concept has been
challenged by direct measurements of cardiac output and
blood flows to various organs in the body. Measurements
of aortic root flow with ultrasonic and electromagnetic
flowmeters indicate that the cardiac output during digestion
of a meal is unchanged from the fasting value (7, 8, 29, 54-
56). Measurements of regional blood flow with flowmeters
indicate that, as compared to fasting levels, the blood
flows through the renal and coronary arteries are unchanged,
whereas, flows through the brachiocephalic and iliac arteries
are decreased during digestion (29, 54, 56). These studies
indicate that during digestion the increased splanchnic
blood flow is due to a redistribution of the cardiac output
at the expense of the flow to the extremities.

Blood flow distribution within the splanchnic
vascular bed during digestion also has been studied (23, 57).
Placement of food into the stomach elicited an increase in
celiac artery flow, followed later, by an increase in
superior mesenteric artery flow; whereas, the infusion of
digested food into the duodenum (bypassing the stomach)
resulted in an increase in superior mesenteric artery flow
and no change in celiac artery flow (23). Also, luminal
placement of digested food in a jejunal segment increased

blood flow to this segment but did not alter flow to the

adjacent segment having no contact with food (57). The
increased flow was mainly due to an increased flow to the
mucosal layer (57). These studies thus suggest that the
postprandial hyperemia in the splanchnic viscera is a
local phenomenon.

The purpose of the present study was twofold:
l) to further evaluate the hypothesis that the intestinal
hyperemia produced by the luminal presence of digested food
is a local phenomenon and 2) to examine the effects of the
concentration (and/or tonicity) of the food in the lumen

and intestinal motility on the local hyperemia.

CHAPTER II

LITERATURE REVIEW

This review of the literature is divided into two

sections, the format of each consisting of an historical

approach. The first section, entitled Feeding and Cir-

 

culatory Adjustments, deals with studies performed on un-

 

anesthetized subjects. Emphasis is placed on the develOp-
ment of views concerning postprandial circulatory adjust-
ments. This section has two subdivisions: a) "Studies

prior to 1966" and b) "Studies after 1966." The second
section, entitled Studies on Isolated Intestinal Segments,
deals with studies in which blood flow of intestinal segments
were measured in anesthetized dogs. Emphasis is placed on
the search for the regulatory mechanisms responsible for the
postprandial intestinal hyperemia.

Feeding and Circulatory
Adjfistments

 

 

(a) "Studies prior to 1966"
One of the earliest studies relating changes in
circulatory hemodynamics with digestion of a meal was that

of Collett and Liljestrand in 1924 (24). Using the nitrous

oxide equilibrium method they measured the cardiac outputs

of two human subjects after a light meal (bread, butter,
cheese, and water) or a heavy meal (smorgasbord, oatmeal
and milk, and beef with fried potatoes). The cardiac out-
put increased an average of 1.5-2.5 liters, thirty to sixty
minutes after a meal (light or heavy), gradually declining
towards fasting levels thereafter. The fasting level was
reached three to four hours after a light meal, taking some-
what longer (up to nine hours) after a heavy meal. An in-
crease in heart rate (5-15 beats/minute) was also noted
thirty to sixty minutes following a light or heavy meal;
and returned to fasting levels three hours after a light
meal, but remaining elevated three hours after a heavy meal.
In 1929 Grollman (33) performed a more extensive
study on variations in cardiac output of men following meals
by using more subjects and also monitoring systemic arterial
pressure. Using an acetylene gas method, he noted an in-
crease in the cardiac output after the ingestion of either
a light meal (bread, meat and a cup of coffee with sugar
and cream) or a heavy meal (bread, meat, sweet chocolate
and 150 cc of milk). The cardiac output increased immediately
and reached a maximum thirty minutes after the ingestion of
a meal. The maximum increases in cardiac output were greater
and of longer duration after a heavy meal (1.0-2.0 liter/min

and lasting for three hours) than after a light meal (0.5-0.9

liter/min and lasting for one hour). Changes in blood
pressure were negligible, whereas, pulse rate increased
transiently and returned to fasting levels within one hour.
Based on this evidence, Grollman suggested that dilation
was occurring in the splanchnic vascular bed with a con-
commitant increase in cardiac output, thus maintaining
systemic pressure virtually unaltered.

In the following years, further studies were carried
out using various gas equilibrium methods which substantiated
the data generated by Collett and Liljestrand (24) and
Grollman (33). In 1931 Starr and Collins (50) using an
ethyliodide gas method noted increases in cardiac output of
50 percent and 20 percent in two human subjects after the
ingestion of a meal. Then, Gladstone in 1935 (31) used a
modified ethylene gas method to measure the cardiac output
of human subjects under basal and postprandial conditions.

He found that during the digestion of a mixed meal of moderate
size, the cardiac output increased by an average of 25 per-
cent (range: 11-47 percent) above basal levels.

Although Grollman (33) had suggested that the
splanchnic vasculature exhibited vasodilation postprandially,
one of the earliest studies to actually measure changes in
splanchnic blood flow during digestion of a meal was per-

formed by Herrick et al. in 1934 (36). They made use of the

 

thermostromuhr method of Rein to measure flow in a single
vessel leaving the liver of a dog (thoracic portion of the
posterior vena cava). A meal of milk (250 cc), eggs (2),
and glucose (1 gm/kg) produced an average increase in blood
flow of about 54 percent, whereas a meal of cooked meat and
cereal resulted in a 74 percent increase in blood flow. The
maximum increase in blood flow occurred within two to three
hours and remained elevated for five to six hours. The same
year Herrick e£_21. (37) using the same method (thermo-
stromuhr) measured flow in the femoral, carotid and superior
mesenteric arteries of conscious dogs during digestion of a
meal. After the ingestion of a milk-egg-glucose meal or a
meal of meat and cereal the superior mesenteric artery blood
flow increased within ten minutes, and reached a maximum of
60 percent above fasting levels within ninety minutes. The
flows in the femoral and carotid arteries also increased by
60 percent above fasting levels after the ingestion of a
milk-egg-glucose mixture. Although they did not measure
cardiac output directly they surmised that an increase in
cardiac output had occurred. Essex §E_gl. in 1936 (28) also
using the thermostromuhr method observed increases in blood
flow through the circumflex branch of the left coronary
artery in conscious dogs of as much as 84 percent after a
meat meal. They suggested that this increase in coronary
flow was due to the increased work load of the heart during

digestion.

The thermostromuhr method was subjected to severe
criticism in the early 19408 (32) forcing investigators to
once again use more indirect methods to study circulatory
adjustments following meals. Abramson and Fierst in 1941
(1) used the venous occlussion plethysmographic method to
follow changes in peripheral blood flow (hand, forearm, and
leg) of human subjects after the ingestion of a protein meal
(lean meat, cottage cheese, egg white and gelatin) or a
carbohydrate meal (vegetables, sweetened stewed and raw
fruits, and sweetened fruit juices). The ingestion of a
carbohydrate meal produced no significant changes in blood
flow to the hand, forearm, or leg. The ingestion of a
protein meal produced an increase in blood flow sixty to
ninety minutes following the ingestion of the meal, first
in the hand, and later, in the forearm and leg. They also
noted an increase in pulse rate and pulse pressure after
ingestion of either meal, suggesting that an augmentation
of cardiac output had occurred.

Berman gt_gl. in 1950 (3) measured changes in cardiac
output with a ballistocardiogram and heart rate with an
electrocardiogram in humans following the ingestion of a
meal (90 gms of carbohydrates, 40 gms of protein, 40 gms of
fat). The cardiac output increased by an average 1.4
liters/minute thirty minutes after the meal, representing

a 24 percent increase. The electrocardiogram indicated that

the heart rate had increased by an average of five beats/
minute thirty minutes after the meal. In the same year,
Paine and Shock (42) using an undamped ballistocardiograph
noted increases in the cardiac index of humans (cardiac out-
put/body surface area) of 12 percent above the basal level
after a meal (33 gms of protein, 110 gms of carbohydrates,
35 gms of fat). This increase persisted for three and one-
half hours and did not return to preprandial levels for five
to six hours.

Brandt g£_§1. in 1955 (4) by means of the bromsulpha-
1ein (BSP) clearance method studied the effect of oral protein
and glucose feeding on splanchnic blood flow in humans. The
estimated splanchnic blood flow increased by 35 percent within
twenty to fifty minutes following the ingestion of a protein
meal (250 gms of chopped beef) and decreased by 8 percent
following the ingestion of a glucose meal (100 gms of glucose
and lemon juice).

Reininger and Sapirstein in 1957 (43) compared the
cardiac outputs and estimated blood flows to the major organs
of fasted (water only ad libitum) and fed (water and food ad
libitum) rats. After an intraperitoneal administration of
nembutal the cardiac output was determined by dye dilution
with Evans blue dye as the indicator and the fractional
distribution of the cardiac output among the organs by ex—

traction ratios of intravenously injected K42. The fasted

10

rats had an average cardiac output of 172 i 38 ml/kg/min,
while the fed rats had an average cardiac output of 223 i

59 ml/kg/min. Blood flows to the liver (34%), gut and
spleen (32%), myocardium (18%), skin (31%), and kidneys (32%)
were all increased in the fed rats suggesting that following
meals all organs increased their blood flows by amounts pro-
portional to the increased cardiac output.

Reininger and Nutik in 1960 (44) using the brom-
sulphalein clearance method studied changes in the cardiac
outputs of unanesthetized dogs upon ingestion of a large
protein meal (116 gms of liver) or an isocaloric fat meal
(73 gms of beef fat). A significant increase in the cardiac
output of 23 percent and 34 percent above fasting values
were noted one and two hours, respectively, after the liver
meal. There were no significant changes found in cardiac
output after the fat meal.

Castenfors e£_gl. in 1961 (10) used the BSP clearance
method to estimate splanchnic blood flow after the ingestion
of 400-500 cc of 20 percent glucose solutions in normal
human subjects and in patients who had been subjected to
partial gastrectomy. Within twenty minutes after the in-
gestion of the hypertonic glucose solution, a 25 percent
increase in splanchnic blood flow was noted in the normal
subjects and a 71 percent increase was noted in the gastrec-

tomized subjects. The pulse rate increased by 94 percent

11

and 30.3 percent in the normal and gastrectomized subjects,
respectively. The systemic pressure was unchanged in the
normal subjects, whereas the blood pressure in gastrecto-
mized subjects decreased leading to circulatory collapse.

In 1961 Rushmer g£_§1. (45) using a new method for
the monitoring of blood flows through individual arteries
obtained results conflicting greatly with the bulk of the
existing data. They monitored blood flows through the
abdominal aorta, renal artery, superior mesenteric artery
and hepatogastric artery of conscious dogs via pulsed ultra-
sonic flowmeters. Following the consumption of a plate of
standard dog food, they noted "a questionable reduction" in
flows through the renal artery and abdominal aorta. They
found no change in the superior mesenteric artery flow and
in only one instance did the flow through the hepatogastric
artery increase following a meal. In 1965 Jones e£_§1. (41)
also published data that was in contrast to previous studies
concerning the effect of feeding on cardiac output. Using
indocyanine green dye and a densitometer, they noted that
twenty minutes following the ingestion of a meal (30%
protein, 30% fat, and 40% carbohydrates), the cardiac index
of human subjects was unaltered from the pre-meal values.

Dagenais g£_21. in 1966 (26) using a dilution
technique (with Coomassie blue dye as the indicator) followed

changes in the cardiac output of men after the ingestion of

12

either a carbohydrate-rich meal or a protein-rich meal.
An electrocardiograph and sphygmomanometer were used to
monitor heart rate and systolic blood pressure respectively.
Of twenty-four human subjects, eight received a protein-rich
meal (480 gms of filet mignon), eight received a carbohydrate-
rich meal (600 gms of apple juice, applesauce, ice cream,
butter cake, and maple syrup) and eight fasted throughout
the study. The subjects fed a protein meal evidenced in-
creases in cardiac output (46%), heart rate (21%), and
systolic pressure (9%). The changes in these parameters
were significantly greater than those of the fasting subjects,
being maximal at 180-270 minutes after the ingestion of the
meal. The subjects fed a carbohydrate-rich meal evidenced
increases in cardiac output of 34 percent and in systolic
pressure of 9 percent, again, being maximal at 180-270 minutes
following the meal. The heart rate also increased 15 percent
within ninety minutes, but returned to control levels by 180
minutes. The fasted subjects evidenced an increase in cardiac
output of 21 percent being maximal at 180-270 minutes.

In summary, most of the studies performed prior to
1966 indicated that the blood flow to the splanchnic viscera
increases postprandially in humans (4, 10), dogs (36, 37),
and rats (43). Only one study yielded data suggesting that
blood flow to the digestive organs of dogs remains unchanged

following a meal (45). A great majority of the investigators

l3

monitoring cardiac output changes occurring after meals
noted an average increase in cardiac output of 25-45 per-
cent in humans (3, 24, 26, 31, 33, 42, 50), dogs (44), and
rats (43) postprandially, whereas, only one study generated
evidence which indicated that the cardiac output was un-
altered in humans (41) after a meal. Furthermore, the
composition of the meal consumed seemed to affect the extent
of the increase in splanchnic blood flow (36, 4), as well as,
the degree and duration of the increase in cardiac output
(24, 26, 33, 44). Splanchnic blood flow tended to increase
to a greater extent after a heavy meal (meat or protein)
than after a light meal (glucose or eggs). The cardiac out-
put increased to a greater extent and remained elevated
longer after a heavy meal (meat or protein) than after a
light meal (glucose or fat). Those studies which measured
systemic arterial pressure and heart rate indicated that the
systemic pressure either remained unaltered (10, 33) or in-
creased slightly (26), and the heart rate increased twenty
to sixty minutes after the ingestion of a meal (24, 33).

It was generally assumed that the increase in Splanchnic
blood flow after meals was a result of an increase in
cardiac output. Additional studies which measured regional
blood flow postprandially in man, dogs, and rats suggested
that the blood flow increased to the extremities (l, 37, 43),

heart (28, 43), kidneys (43), and brain (37, 43) in addition

14
to the splanchnic viscera. Only one study noted "a
questionable reduction in renal blood flow"; however, the~
same study indicated that the blood flow to the digestive
organs remained unaltered following a meal (45). Thus, the
prevalent concept of cardiovascular adjustments postprandially
held that, after meals, there was an augmentation of cardiac

output which was shared by all the major organs of the body.

(b) "Studies after 1966"

After 1966 many investigators used various blood
flowmeters to study cardiovascular responses to meals in
conscious animals. These flowmeters allowed the direct
monitoring of blood flow through individual vessels. Burns
and Schenk in 1967 and 1969 (7, 8) monitored blood flows
through the superior mesenteric artery and the ascending
aorta of conscious dogs with implanted electromagnetic blood
flow transducers. After the ingestion of a meal (15 ounces
of horsemeat) the cardiac output was unaltered (as inferred
from the blood flow through the ascending aorta) whereas,
the superior mesenteric artery flow began to increase within
five minutes after ingestion reaching a plateau fifty minutes
later (average peak flows being 71% above fasting levels).
In this study, the fasting superior mesenteric artery flow
was 7.5 percent of the cardiac output, but it increased to

14.6 percent during digestion.

15

A more in-depth study of the cardiovascular
(systemic and regional) responses to anticipation, ingestion
and digestion of food was reported by Fronek and Stahlgren
in 1968 (29). The cardiac output and flows through the
brachiocephalic, superior mesenteric, and external iliac
arteries of conscious dogs were measured with implanted
electromagnetic flow transducers. Systemic pressure and
heart rate were monitored by a catheter implanted into the
descending aorta. Following an eighteen-hour fast, a can
of dog food (450 gms) was presented to the animals. During
the anticipation period cardiac output, systemic pressure,
heart rate and flows through the brachiocephalic and external
iliac arteries increased significantly, whereas, superior
mesenteric artery flow remained unaltered. During ingestion
of the meal, cardiac output, systemic pressure and heart
rate continued to rise reaching a maximum during the first
minute after starting ingestion. Also, during the first
minutes of ingestion, flow in the brachiocephalic artery
continued to increase, whereas superior mesenteric artery
flow began to increase and external iliac artery flow began
to decrease. By one hour after feeding the cardiac output,
blood pressure and flows through the brachiocephalic and
external iliac arteries had returned to prefeeding levels;
heart rate remained slightly elevated and the superior

mesenteric artery reached its maximum increase in flow (33%).

16

By the third hour after ingestion blood pressure, heart

rate and cardiac output were at control levels, with superior
mesenteric artery flow still 30 percent above control levels,
and brachiocephalic and external iliac artery flows de-
creasing to 80 percent and 75 percent of control levels,
respectively. They suggested that the observed changes in
the measured hemodynamic variables during the anticipation
and ingestion of food could be attributed to a generalized
sympathetic response, whereas during digestion a selective
increase in flow occurs in the superior mesenteric artery

at the expense of the vascular beds supplied by the external
iliac and brachiocephalic arteries.

Vatner §E_gl. in 1969 (54) using pulsed ultrasonic
or electromagnetic flowmeters placed on the ascending aorta,
mesenteric, renal and iliac arteries and blood pressure
transducers in the aorta studied the hemodynamic responses
to meals in unanesthetized dogs and baboons. They found
transient increases in blood pressure, heart rate and cardiac
output during the presentation of food, which returned to
control levels fifteen minutes after ingestion. Mesenteric
flow increased after ingestion (with a 300% increase above
fasting levels occurring within one hour) and remained
elevated for six hours. Renal artery flow was essentially
unchanged, but iliac flow fell as much as 20 percent below

fasting levels. The same group (Vatner et al.) in 1970 (55),

17

placed flowmeters of various types on the ascending aorta
and on the cranial mesenteric artery of dogs for the measure-
ment of cardiac output and mesenteric flow respectively
prior to and after the ingestion of a variety of meals
(meat-flavored dog food, condensed milk, horsemeat and
gravy, raw or cooked hamburger, dry dog food and beef fat).
Pressure gauges were attached either directly to the aorta
or to a femoral cannula for the monitoring of systemic
pressure and heart rate. Anticipation and ingestion of the
meals resulted in increases in heart rate (79%), cardiac
output (63%) and aortic blood pressure (31%), whereas,
mesenteric flow transiently decreased (10%). Cardiac output,
heart rate and blood pressure returned to control levels
after 10-30 minutes, whereas superior mesenteric artery flow
had begun to increase. Superior mesenteric artery flow
reached a maximum (15%-200% above fasting levels) fifty to
sixty minutes after ingestion of food, and then returned
gradually to control levels within three to seven hours
after ingestion of food. In fasted, muzzled dogs the pre-
sentation of food, but not allowing the dogs to eat, also
produced an increase in mesenteric resistance on seeing the
food and a decrease in resistance fifteen minutes later.

The decreased resistance returned to control levels within
thirty minutes after the presentation of food. The increase

and decrease in mesenteric resistance in these dogs, however,

18

were less marked than those which occurred when they were
allowed to eat and rest after eating. Alpha-adrenergic
blockade (phenoxybenzamine, 15 mg/kg, i.v.) or beta-
adrenergic blockade (propanolol hydrochloride, 3 mg/kg,
i.v.), respectively, reversed or attenuated the circulatory
responses during anticipation of food. Neither alpha- nor
beta-adrenergic blockade altered the mesenteric vasodilation
during digestion. Cholinergic blockade (atropine, 0.1-0.2
mg/kg, i.v.) prevented the postprandial mesenteric vaso-
dilation, whereas, bilateral vagotomy did not.

Vatner g£_gl. in 1970 (56) in an extended study
using the same techniques as in earlier studies (54, 55)
measured cardiac output, blood pressure, heart rate and
flows through the cranial mesenteric artery, left renal
artery, left iliac artery and left circumflex coronary
artery. During the presentation and ingestion of food,
cardiac output (62%), blood pressure (33%), and heart rate
(79%) all increased; but, returned to control levels within
ten to thirty minutes and remained there up to seven hours
postprandially. The mesenteric, iliac and renal vascular
beds evidenced similar responses during anticipation, in-
gestion, and digestion of food as reported earlier by the
same author (54, 55). The left circumflex coronary flow
increased during the anticipation and ingestion of food,

returned to control levels within fifteen to twenty minutes,

19

and remained at fasting levels throughout the remainder
of the study.

In summary, the use of more sophisticated instru-
mentation and methodology in the studies undertaken after
1966 yielded results which were both supportive and contra-
dictory of earlier studies. The direct measurement of blood
flow through the superior mesenteric artery of either dogs
(7, 8, 29, 54, 56) or baboons (54) with flowmeters strongly
supported the earlier supposition that splanchnic vaso-
dilation occurs postprandially. More specifically, during
anticipation and ingestion of food the superior mesenteric
artery flow remained unaltered (29) or decreased slightly
(55), then began to increase within five to fifteen minutes
(7, 29), attained a maximum fifty to sixty minutes after the
ingestion of a meal (7, 29, 54, 55), and remained elevated
for three to seven hours. In contrast to earlier studies
direct measurement of aortic root flow indicated that the
cardiac output remains essentially unaltered during digestion
of a meal (barring transient increases during anticipation
and ingestion of food) (7, 8, 29, 54, 56). The systemic
pressure and heart rate followed the same general pattern
of changes as did the cardiac output (29, 54-56). Direct
measurements of regional blood flow (excluding the splanchnic
vascular bed) also yielded results different from those of

earlier studies. Blood flow through the renal and coronary

20

arteries remained unaltered during digestion of a meal
(54, 56), whereas, blood flows through the brachiocephalic
and external iliac arteries (representing flow through the
skin and musculature of the extremities, respectively)
tended to decrease (29, 55). Thus, recent evidence suggests 3““fi
that rather than an augmentation of cardiac output resulting
in an increase in blood flow to all vascular beds, there is
a redistribution of an unchanged cardiac output, postprandi-

ally, favoring the splanchnic vascular bed at the expense of

 

blood flow to the extremities. It appears that the transient
cardiovascular responses which occur during the anticipation
and ingestion of a meal are mediated via the sympathetic
nervous system; while those occurring during digestion may
be mediated by some Cholinergic system other than the vagi
(55).

Studies on Isolated
Intestifial Segments

 

 

Brodie and Vogt in 1910 (5) used the oncometric
method (a modification of the plethysmographic method) to
study blood flow through an isolated intestinal loop (125 cm
long) of chloroform anesthetized dogs prior to and after the
intraluminal placement of water and salt solutions. The
intraluminal placement of water caused a gradual decrease

in flow as was the case when the intestinal segment was empty.

21

Saline solutions (between 0.9-1.3%) caused a slight increase
in flow in two of the three animals. When a 2 percent
solution of NaCl was placed in the lumen, a striking in-
crease in blood flow of 200 percent was observed within
twelve minutes and remained at that level for one hour.
Magnesium sulfate (47%) caused an increase in flow of over
11.2 percent by twenty minutes after placement. The maximum
increase in flow observed during any procedure was 1.3 cc/

gm/min. The volumes of the test solutions upon removal

 

suggested that water and NaCl were absorbed; whereas,
magnesium sulfate caused exsorption of fluid. They concluded
that when the intestine was actively involved in absorption
or secretion, blood flow to the intestine increased by 39
percent over basal levels. In the same year Brodie g£_31.
(6) using the same method (oncometric) studied blood flow
changes in an isolated loop of the intestine of chloroform
anesthetized dogs after the intraluminal placement of Witte's
peptone (10% in normal saline). The blood flow through the
intestinal 100p was increased by 66 percent, 57 percent,
and 28 percent above control levels eighteen, forty, and
sixty minutes after the placement of the peptone solutions.
Fifty years passed during which no studies con-
cerned with gut lumen contents and intestinal blood flow

were performed using isolated in situ intestinal segments.

22

By the late 19503 the growing clinical interest in the

"dumping syndrome" necessitated experimental situations
which would simulate the clinical manifestations. Thus,
Huse and Henshaw in 1960 (40) used electromagnetic flow-
meters to study changes in the blood flows through the i
mesenteric, renal, carotid and femoral arteries of penta-
barbital anesthetized dogs after the injection of 50 cc of

50 percent glucose into the proximal jejunum. The mesenteric

 

artery flow increased an average of 45 percent, with maximal
increases occurring between twenty and thirty-five minutes
after the glucose injection. In contrast, there was an
average decrease of 36 percent in carotid flow, 34 percent

in renal flow, and 32 percent in femoral flow. Cardiac
outputs (determined by a dilutional technique using reno-
grafin) decreased by 20 percent. Based on these results

they suggested that there was a redistribution of the cardiac
output favoring the splanchnic bed at the expense of blood
flow to other areas.

In 1967 Swan and Grafe (51) used electromagnetic
flowmeters to study changes in blood flow through the
superior mesenteric artery upon injection of 150 m1 of 50
percent dextrose into the proximal jejunum of pentobarbital
anesthetized dogs. The mean mesenteric blood flow increased
within minutes after the injection, reaching a value 52 per-

cent above fasting levels by ninety minutes (accompanied

23

by a fall in mesenteric vascular resistance of 36 percent).
The increases in mesenteric flow persisted for 150 minutes.
Other studies were carried out using isolated

jejunal segments and different methods of measuring changes
in blood flow which, in general, substantiated the data
obtained with flowmeters. Varro g£_21. in 1967 (53)
measured venous outflow from an isolated denervated jejunal
loop of chloralose anesthetized dOgs while introducing

isotonic solutions of saline, glucose, or glycine into the

 

lumen. When isotonic glucose was in the lumen the jejunal
blood flow increased to 20 percent above the control flow
values. The introduction of an isotonic glycine solution
resulted in a 55 percent increase in blood flow from the
control flow values. The intraluminal injection of isotonic
saline produced an increase in intestinal blood flow of 21
percent. The introduction of a comparable amount of air
into the jejunal lumen produced no significant change in
blood flow. Chou g£_al. in 1967 (15) measured the changes
in venous outflow from isolated naturally perfused in BEES
jejunal segments of anesthetized dogs following luminal
placement of 2.5 percent, 5.0 percent, 20 percent, or 50
percent glucose solutions. Polyethylene glycol (PEG) was
used as a control solution. The 20 and 50 percent glucose
solutions increased the venous outflow over precontrol levels

by 9 and 18 percent, respectively. The 2.5 percent and 5.0

24

percent glucose solutions, although failing to increase
the venous outflow above precontrol levels, did increase
the flow over postcontrol levels. Van Heerden g£_al. in
1968 (52) using the I33 clearance technique measured blood
flow from an isolated loop of the proximal jejunum of pento- 5&4“
barbital anesthetized dogs while perfusing the lumen with

5 percent or 25 percent glucose solutions at 4 cc/min for
one hour. They found no significant increase in blood flow

while perfusing the 100p with 5 percent glucose, but a 52

 

percent increase in flow while perfusing with 25 percent
glucose. They also used two differently labeled micrOSpheres
Sr and Sc (as control and test respectively) to determine the
distribution of blood flow in different sections of the in-
testine during luminal perfusion of a jejunal loop with 25
percent glucose solutions. It was noted that all portions

of the intestine possessed similar amounts of radioactivity
prior to the glucose perfusion. During the perfusion of the
lumen with hypertonic glucose, it was found that the section
containing 25 percent glucose possessed 54 percent greater
radioactivity than did the nonperfused section.

Since electrolytes are continuously secreted and
absorbed by the gastrointestinal tract, the effects of
intraluminal placement of salt solutions isosmotic or hyper-
tonic on the local blood flow were assessed. Chou g£_§1. in

1968 (16) studied the effects of intraluminal placement of

25

isosmotic solutions of NaCl, KCl, MgClZ, and CaCI2, on the
venous outflow and the luminal pressures of two naturally
perfused in gitg ileal segments of anesthetized dogs. One
segment served as the test segment and contained one of
the four isosmotic salt solutions while the other segment
served as the control segment and contained an isosmotic
polyethylene glycol solution. As compared to the changes
occurring in the control segment, the intraluminal place-
ment of the salt solutions produced the following results.
The venous outflow was decreased by NaCl and MgCl2 solutions,
unchanged by the CaCl2 solution, and increased by the KCl
solution. The motility was increased (as inferred from
changes in luminal pressure) only by the KCl solution.
Dabney g£_31. 1969, (25) using two naturally perfused iso-
lated ileal segments of anesthetized dogs studied the effects
on ileal venous outflow of placing hypertonic salt solutions
in the lumen. Hypertonic KCl, MgClz, CaC12, NaCl, and poly-
ethylene glycol (PEG) solutions (all 1500 mOsm/kg) increased
the venous outflow, with hypertonic KCl causing the greatest
increase and hypertonic PEG causing the least increase in
venous outflow.

Chen g£_gl. in 1969 (11) assessed the possibility
that the local hyperemia produced by the luminal presence
of hyperosmotic salt solutions is mediated by mucosal nerves.

They compared the effects of intraluminal placement of NaCl,

26

KCl, MgCl , or CaCl (all 1500 mOsm/kg) on the luminal

2 2
pressures, and the volume, osmolarity, and cation concen-
trations of the venous outflow from two adjacent gut seg-
ments of anesthetized dogs. The luminal presence of any
of these solutions significantly increased the volume, as
well as, the cation concentration of the venous outflow.
They repeated the procedure after anesthetizing the mucosa
with 0.4 percent dibucaine. After the dibucaine treatment
KCl significantly decreased venous outflow, NaCl and CaCl

2
failed to increase venous outflow, while MgCl increased

2

venous outflow to the same extent as before the dibucaine
treatment. The cation concentration following KCl or MgCl2
placement increased to greater levels than observed prior
to the dibucaine treatment. The rise in cation concentration
with NaCl or CaCl2 in the lumen was the same before and after
the dibucaine treatment. The increases in venous osmolarity
were the same before and after the treatment for all salt
solutions studied. They concluded that the mucosal nerves
are partly responsible for the local hyperemia produced by
luminal placement of hyperosmotic salt solutions.

Hsieh et_§1. in 1970 (38) measured the venous out-
flow and luminal pressure of an in §i£2_duodenal segment of
anesthetized dogs while perfusing the lumen with acidified

Tyrode's solutions (pH 3.0, pH 2.5, pH 2.0, and pH 1.5) and

glucose solutions (5% and 50%) at 4 ml/min for sixteen minutes.

 

 

27

The Tyrode's solutions of pH 2.0 and pH 1.5 increased the
venous outflow above the control flow (with Tyrode's pH 7.4
in the lumen) by 10.1 percent and 17.7 percent, respectively.
The 50 percent glucose solution increased the venous outflow
by 13.1 percent. The duodenal motility was increased by the
Tyrode's solution of pH 1.5. The Tyrode's solutions of pH
3.0 and pH 2.5 and the 5 percent glucose solutions did not
effect duodenal blood flow. These results were essentially
the same as those noted by Chou gt_31. 1970 (17). Chou §£_gl.
1971 (19) further investigated the effects of lumen pH and
osmolarity on duodenal blood flow. The perfusion of Tyrode's
solutions of pH 8.0, pH 9.0 or pH 11.0 into the lumen of
i2_gi£g duodenal segments of anesthetized dogs at 4 cc/min
for sixteen minutes failed to change the venous outflow.
Perfusion with glucose solutions (1100 and 1500 mOsm/kg) also
did not alter the duodenal venous outflow.

Burns g£_al. in 1971 (9) investigated the role of
local nerves in the regulation of local jejunal blood flow
and/or motility when 10 m1 of hyperosmotic KCl, NaCl (1500
mOsm/kg) or glucose (3000 mOsm/kg) were in the lumen. Iso-
tonic polyethylene glycol was used as the control solution.
The intraluminal placement of any of the test solutions
(KCl, NaC1, or glucose) resulted in an increase in venous
outflow and a decrease in vascular resistance. During the

local intra-arterial infusion of tetrodotoxin (a neurotoxin)

28

the intraluminal placement of KCl increased vascular
resistance, NaCl either decreased or did not alter resis-
tance, but glucose still decreased resistance. Tetro-
dotoxin abolished the increased motility caused by NaCl
and glucose and attenuated that caused by KCl. They con- r
cluded that vascular and motility responses to lumen hyper-
tonicity are, in part, mediated by intramural nerves.

In 1971, Chou §E_21. (18) examined some of the

possible mechanisms involved in the local intestinal hyper-

 

emia produced by the luminal presence of hyperosmotic glu-
cose solutions. Using two adjacent jejunal segments of
anesthetized dogs, they compared the effects of intraluminal
placement of 2.5, 5.4, 20 and 50 percent glucose solutions
and 8.5, 34 and 85 percent polyethylene glycol solutions on
the volume, osmolarity, and glucose concentration of the
venous outflows and the luminal pressures of the two segments.
The intraluminal placement of all the glucose solutions in-
creased the volume and glucose concentration of the venous
outflow. The venous osmolarity was increased to the same
extent by hypertonic polyethylene glycol solutions as by the
hypertonic glucose solutions of the same osmolarity. How-
ever, the 34 percent polyethylene glycol solution (osmoti-
cally comparable to the 20% glucose solution) did not alter
the venous outflow and the 85 percent polyethylene glycol

solution (osmotically comparable to the 50% glucose solution)

29

increased flow to a lesser extent than did the 50 percent
glucose solution. All the hypertonic solutions studied
increased jejunal motility. Local intra-arterial infusion
of 2.5 percent and 5.4 percent glucose solutions increased
the venous glucose concentrations to levels comparable to
those caused by the intraluminal placement of any glucose
solution, but did not alter the venous outflow of the jejunal
segments. In the same study they reexamined the local in-
crease in venous outflow produced by the intraluminal place-
ment of 50 percent glucose after exposing the jejunal mucosa
to 0.4 percent dibucaine (a local anesthetic). After the
dibucaine treatment the increase in flow produced by the 50
percent glucose solution was either abolished or attenuated
as was the jejunal motility. They concluded that the in-
crease in flow with hypertonic glucose in the jejunal lumen
is a local phenomenon. The local hyperemia is not a result
of hyperglycemia, but may be mediated by: 1) local vascular
hypertonicity and 2) mechanisms which can be blocked by
anesthetizing the mucosa.

Hsieh and Chou in 1972 (39) used a bioassay method
to investigate the possible role of humoral substances in
the local increase in blood flow and motility when either
acid or foodstuff was in the duodenal lumen of anesthetized
dogs. The bioassay organ was an isolated segment of jejunum

which was pump perfused with duodenal venous blood while

 

30

acidified Tyrode's solution (pH 1.5) or a liquid diet food
(Sego) was being infused into the duodenal lumen. The
results indicated that, while acidified Tyrode's or Sego
(diet food mixture) was in the duodenal lumen, the local
vascular resistance decreased and its motility increased.
Simultaneously, the vascular resistance of the assayed
jejunal segment decreased and its motility increased. They
concluded that humoral substances which could lower vascular
resistance and increase motility appeared in the duodenal
venous blood when the lumen contained acid or foodstuff.

That same year Chou gt_gl. (20) studied the effects of the
local intra-arterial infusion of secretin, cholecystokinin
and pentagastrin on the vascular resistances of duodenal and
jejunal segments, spleen, whole forelimb, and muscle and

skin of the forelimb of anesthetized dogs. Secretin decreased
the vascular resistance of all organs studied (~10%) when the
local blood concentration of secretin was raised by 0.01 u/ml.
Cholecystokinin (CCK) decreased the vascular resistances of
the duodenal and jejunal segments (-20%) when the local blood
concentration of CCK was raised by 0.05 u/ml. CCK did not
alter the vascular resistance of the forelimb, skin, or
muscle. Gastrin decreased the vascular resistance of the
duodenal and jejunal segments (-l4%) when the local blood
concentration of gastrin was raised by 0.04 ug/ml. Gastrin

had no effect on the splenic resistance. They concluded that

31

the vasodilator action of secretin is equipotent in the
duodenum, jejunum, spleen, skin, and muscle; while that of
cholecystokinin is greater in the gut than in the spleen
and absent in the forelimb. Gastrin dilates the gut vascu-
lature, but does not alter the splenic vasculature.

In 1973, Chou g£_21. (22) studied the effects of
the hormones secretin, pentagastrin and cholecystokinin on
the vascular resistance of the heart and kidney. While the
left coronary or renal artery of pentobarbital anesthetized
dogs were pump perfused at a constant rate, the hormones
were infused at various rates into the local arteries.
Secretin decreased the resistance of the coronary (-13%)
and renal (-9%) vasculatures when the local blood concentra-
tion of secretin was raised by 0.03 u/ml and 0.01 u/ml re—
spectively. These responses were not as great as the response
produced by secretin in the duodenal, jejunal, splenic, fore-
limb, skin and muscle vasculatures studied earlier (21).
Increments in the local concentration of cholecystokinin
over the ranges 0.006-0.l3 u/ml and pentagastrin over the
ranges 0.04-0.85 ug/ml did not significantly alter coronary
or renal vascular resistance. They concluded that the G.I.
hormones exert little or no influence on the vascular re—
sistance of the heart or kidney.

Some of the previous studies using isolated in EiEB

intestinal segments suggested that the increase in flow

32

produced by the intraluminal presence of foodstuffs,
nutrients, or electrolytes was a local phenomenon. Thus,
Chou g£_31, in 1974 (23) studied the time course of the
changes in blood flow through the celiac and superior
mesenteric arteries in chloralose anesthetized dags, during
the infusion of food into the stomach (200 ml in 3 minutes)
or during the infusion of digested food into the duodenum,
at 4 cc/min. Introduction of food into the stomach increased
the celiac artery blood flow within five minutes and the
hyperemia was maintained for thirty minutes, after which,
the flow gradually returned to control levels. In contrast,
the flow in the superior mesenteric artery (SMA) remained
at control levels until thirty minutes after the introduction
of food into the stomach, at which time, it increased and
remained elevated for at least three hours. The infusion of
digested food into the duodenal lumen resulted in an increase
in blood flow through the SMA within three minutes after
starting the infusion and remained elevated throughout the
infusion. The blood flow in the celiac artery was unaltered
throughout the infusion period.

In summary, in the early 1900's Brodie and Vogt
suggested that when the intestine is actively involved in
the process of absorption or secretion its blood flow in-
creases (5). Since then, many studies have suggested that

the postprandial increase in blood flow to the gut is a

33

local phenomenon involving only the portion of the intestine
which is in contact with foodstuff (food, glucose, salts,
etc.) (15, 16, 18, 23, 25, 52). By the use of isolated
i§_§i£g intestinal segments investigators attempted to
elucidate the possible mechanisms which regulate the local
gut blood flow.

The pH of the gut contents appeared to affect its

local blood flow. When the pH of a solution (Tyrode's)

perfusing the duodenal lumen was lowered below 2.0 the
motility and local blood flow of the duodenum was increased
(17, 38). When the pH of the same perfusate was raised above
11.0 there was no change in the local blood flow or wall
activity of the duodenum (l9).

Intraluminal placement of hypo- or isotonic glucose
solutions into the jejunal lumen either increased (15, 18,
53) or did not alter the blood flow (52), whereas, perfusion
of isotonic glucose through the duodenal lumen did not alter
local blood flow (38). The placement of an isotonic glycine
solution into the jejunal lumen increased the blood flow (53).
Isotonic salt solutions in the jejunal (53) or ileal (16)
lumen decreased or did not alter local blood flow, with the
exception of potassium salts which increased the flow (16).
Hypertonic glucose or salt solutions in the duodenum, jejunum
or ileum all increased local blood flow (9, ll, 15, 18, 25,

38, 40, 51, 52). Intraluminal placement of a hypertonic

34

solution (3000 mOsm/kg) of a nonabsorbable substance,
polyethlene glycol into the jejunal lumen also resulted

in an increase in local blood flow (18, 25). The hyperemia
produced by all the hypertonic solutions was associated
with increases in the venous osmolality (ll, 18) and in w
some cases, the motility of the intestinal segments (9, E
18). The luminal placement of all absorbable hypertonic
solutions (salts and glucose) resulted in elevations of

the local blood concentrations of the respective chemicals

 

(ll, 18).

The participation of local nerves in the initiation
of the local hyperemia produced by the intraluminal presence
of hyperosmotic substances was investigated with the use of
an anesthetic or a neurotoxin. The application of dibucaine
(a local anesthetic) to the mucosal surface abolished or
attenuated the increase in blood flow produced by the intra-
luminal placement of hyperosmotic glucose, KCl, NaCl, or
CaCl2 (11, 18), but was ineffective in altering the hyper-
emia produced by hyperosmotic MgCl2 (11). The treatment
with dibucaine also prevented the increase in motility
observed with hypertonic glucose in the lumen (18). The
increased cation and glucose concentrations of the local
venous blood caused by luminal placement of the hyperosmotic
salt and glucose solutions were unaltered or increased by

the dibucaine treatments (11, 18). The local intra-arterial

35

infusions of tetrodotoxin (a neurotoxin) abolished the
increase in local blood flow produced by the intraluminal
placement of hypertonic KCl and NaCl solutions, but did not
affect the hyperemia produced by hypertonic glucose (9).
Tetrodotoxin also either attenuated or abolished the in- 1
crease in intestinal motility when the solutions were in
the lumen.

The possible implication of gastro-intestinal

 

hormones in the local intestinal hyperemia was established
by a bioassay method (39). Local intra-arterial infusions
of secretin, cholecystokinin, or pentagastrin produced
dilation of duodenal and jejunal vasculatures (20), but had

little or no effect on the heart or kidney vasculature (22).

CHAPTER III

METHODS

The purpose of the present study was twofold:
l) to further evaluate the hypothesis that the intestinal
hyperemia produced by the presence of digested food is a
local phenomenon and 2) to examine the effects of the con-
centration (and/or tonicity) of the food in the lumen and
the intestinal motility on the local hyperemia. To meet
this purpose three series of experiments were performed
using two different surgical preparations. A total of
twenty-four mongrel dogs (10-20 kg in weight), which had
been fasted for twenty-four hours were used. The animals
were anesthetized by an intravenous administration of either
a chloralose-urethane mixture (75 mg chloralose and 500 mg
urethane/kg) or sodium pentobarbital (30 mg/kg). They were
artifically ventilated with room air via an endotracheal
tube with a positive pressure respiration pump (Harvard,
Model 607, Dover, Mass.). The systemic arterial pressure
was continuously monitored via a cannula in the femoral
artery with a pressure transducer (Statham, p23 Gb, Hato
Rey, Puerto Rico) and recorded on a direct writing oscillo-

graph (Sanborn, 7700 Series, Waltham, Mass.).

36

 

37

Preparation of the Diggsted
Dongood Mixtures and Their
Supernatants

 

One can of beef dog food (Alpo, Allen Products
Co., Inc., Allentown, Pa.) was emptied into a high-speed
blender and vigorously mixed until a homogenous blend was
formed. The pH of the homogenate was adjusted to approxi-
mately 7.0 (6.8-7.2) with sodium hydroxide. To the blend,
750 mg of pancreatic enzymes (Viokase, Viobin Corp.,
Monticello, Ill.) were added for the hydrolysis of the
major food constituents (protein, starch, and fat). To
facilitate the digestion of the food, the mixture was gently
stirred on a magnetic stirrer (Arthur H. Thomas, Model 15,
Philadelphia, Pa.) for five to six hours at room temperature.
From the i2_yi££g digested food, four different food mixtures
were prepared: undiluted digested food (1:0 Food), 1:2 di-
luted digested food (1:2 Food), 1:4 diluted digested food
(1:4 Food), and 1:9 diluted digested food (1:9 Food). Dis-
tilled water was used to dilute the digested food.

Four cans of digested food were homogenized and the
homogenate of each can was divided into two halves. One
half of the homogenate was used to prepare the four digested
food mixtures in the same manner as described above. Samples
of the four food mixtures were centrifuged at 19,250 x G,
the supernatants removed and their osmolalities determined

by the freezing point depression method with an osmometer

38

(Advanced Instruments, Inc., Model 67-31LAS, Newton Highlands,
Mass.). The other half of the homogenate was refrigerated
for 24 hours and then treated in the same manner as the first

half of the homogenate.

Control Solutions

Isosmotic solutions of polyethylene glycol (PEG;
molecular weight 4000) and sodium chloride (normal saline)
were used as controls for the food mixtures. Both the
control solutions and the food mixtures were kept in a
constant temperature water bath (Precision Scientific Co.,
Chicago, Ill.) at 37°.

Surgical and Experimental
Procedures

(A) Preparation I

In sixteen dogs, under chloralose-urethane anesthesia,
the abdominal cavity was exposed through a midline incision.
The superior mesenteric artery was located and approximately
2-2.5 cm of the artery was dissected free from the adjacent
tissue. A noncannulating electromagnetic blood flow trans—
ducer (Series 5000, Biotronex Laboratory, Inc., Silver
Springs, Md.) was fitted snugly around the artery and
grounded to adjacent tissue. For the determination of zero
flow, a hydraulic occluder of silastic was placed around the

artery distal to the flow transducer. The electromagnetic

39

flow transducer was attached to a pulsed-logic flowmeter
(Biotronex Laboratory, Inc., Silver Springs, Md.). The
flowmeter was electronically calibrated with a direct
writing oscillograph (Sanborn, 770 Series, Waltham, Mass.)
for the continuous recording of blood flow through the
superior mesenteric artery. Previous volume calibrations,
performed with a beaker and stOp watch in yitrg (with normal
saline) and in yiyg (in a few representative animals), had
verified the accuracy and linearity of the flow transducers.

The proximal duodenum was located and an L-shaped
plastic tube (i.d. = 3.5 mm, o.d. = 6.5 mm) was inserted
into the duodenal lumen. The tube was secured in place such
that the opened end, inside the duodenum, faced the aboral
portion of the small intestine. The tube was used to deliver
digested food into the duodenal lumen with a pump (Sigma-
motor, Model TM 10, Middleport, NY). Using the natural
vascular pattern of the mesentery as a guide, a segment of
jejunum about 10-12 cm in length and 30-35 cm aboral to the
ligament of Treitz was isolated. A plastic tube (i.d. = 1.1
cm, o.d. = 1.6 cm) was inserted into the cut end of the
jejunum proximal to the isolated segment to allow for drain-
age of the food being pumped through the duodenal—jejunal
portion of the intestine (60-70 cm in length).

The isolated in_§i£3_jejunal segment had a blood

supply which stemmed from a single artery and was drained

40

by a single vein. After an intravenous administration of

an anticoagulant (heparin sodium, 6 mg/kg), the vein drain-
ing the segment was exposed and cannulated with polyethylene
tubing (i.d. = 1.7 mm, o.d. = 2.4 mm). During the cannula—
tion procedure, care was taken to insure that the artery “TE“
and nerves were not disturbed. The venous blood draining

the segment was collected in a reservoir initially contain-

ing 200 m1 of 6 percent dextran in normal saline. The blood

 

was continuously returned to the dog from the reservoir with

til—Emu-

a variable-speed pump (Sigmamotor, Model T6 SH, Middleport,
NY) via a cannulated femoral vein at a rate equal to the
venous outflow. A rubber tube (i.d. = 3 cm, o.d. = 0.5 cm)
was placed into the lumen of the isolated segment for the
introduction and withdrawal of fluids. Both ends of the
segment were tied and the mesentery cut to exclude collateral
blood flow. The naturally perfused in 3333 jejunal segment,
outside the abdominal cavity, was covered with a plastic
sheet to maintain a moist environment and kept at 37°C via
a heating lamp.

Using the preparation described above the blood
flows through the superior mesenteric artery and the iso-
lated jejunal segment were simultaneously measured during
two series of experimental maneuvers: l) luminal perfusion

of the duodenal-jejunal portion of the intestine with food

41

(Series 1) and 2) placement of food into the isolated

jejunal segment (Series 2).

Series 1

Ten ml of isosmotic PEG was placed into the isolated
jejunal segment. When the blood flow through the superior
mesenteric artery and the venous outflow from the jejunal
segment became stable, undiluted digested food was pumped

into the duodenal lumen at 4 cc/min for one hour. While

 

the food was traversing the duodenal-jejunal portion of the
intestine, the isolated jejunal segment retained the isos-
motic PEG in its lumen. The blood flow through the superior
mesenteric artery was continuously recorded and one-minute
samples of the venous outflow from the jejunal segment were
collected with a graduated cylinder at 5, 15, 20, 25, 35,

50 and 60 minutes after the start of the perfusion. The
volume of blood in the graduate cylinder was recorded and
returned to the reservoir after each collection. This pro-

cedure was executed in a total of six dogs.

Series 2

Ten ml of isosmotic PEG was placed into the iso-
lated jejunal segment. When the blood flow through the
superior mesenteric artery and the venous outflow from the
jejunal segment became stable, the PEG solution was with-

drawn and 10 m1 of undiluted digested food was introduced

42

into the jejunal lumen. The food remained in the jejunal
lumen for fifteen minutes during which, blood flow through
the superior mesenteric artery was continuously recorded,

and one-minute samples of the venous outflow from the

jejunal segment were collected with a graduated cylinder 1.-

at 6, 9, 12 and 15 minutes following the introduction of

the digested food. The volume of blood in the graduate

 

cylinder was recorded and returned to the reservoir after ,
each collection period. This procedure was executed in a f

total of ten dogs.

(B) Preparation II

In eight dogs, under sodium pentobarbital anesthesia,
the abdominal cavity was exposed through a midline incision.
A 100p of jejunum about 25-30 cm aboral to the ligament of
Treitz was exteriorized. The jejunal loop was divided into
two segments of equal length such that the blood flow from
each segment was drained by a single vein. After an intra-
venous administration of heparin sodium (6 mg/kg), the vein
draining each segment was cannulated with polyethylene
tubing (i.d. = 1.7 mm, o.d. = 2.4 mm). Care was taken to
insure that the arteries and nerves remained intact. The
venous blood draining the two segments was directed into a
reservoir initially containing 200 m1 of 6 percent dextran

in normal saline. The blood was continuously pumped back

43

from the reservoir to the dogs via a cannulated femoral
vein at a rate equal to the total venous outflow. A rubber
tube (i.d. = 0.3 cm, o.d. = 0.5 cm) was placed into the
lumen of each segment for the introduction and withdrawal
of fluids. At all other times the tubes were used for the lr-u—
monitoring of the luminal pressures of the segments. The I
luminal pressures were measured with pressure transducers
(Statham, p23 Gb, Hato Rey, Puerto Rico) and recorded on a

direct writing oscillograph (Sanborn, 7700 Series, Waltham,

 

Mass.). Both ends of each segment were tied and the
mesentery cut to exclude collateral blood flow. The
naturally perfused in sitg_jejunal segments, outside the
abdominal cavity, were covered with a plastic sheet to
maintain a moist environment and kept at 37°C via a heating
lamp.

Using this double jejunal segment preparation, a
series of experiments were done to compare the effects of
luminal placement of the four food mixtures (i.e., un-
diluted food, 1:2, 1:4, or 1:9 diluted food) on the volume
and osmolality of the venous outflow, changes in the placed
volumes, and luminal pressures of the segments. One of
the two segments was used as the experimental segment and
the other segment was used as the control segment. Each
experiment consisted of three successive fifteen minute

periods (precontrol, test, and postcontrol). During the

44

precontrol and postcontrol periods, 10 m1 of normal saline
were introduced into the lumen of both segments. During
the test period, 10 m1 of either undiluted digested food
or one of the dilutions of digested food were introduced
into the experimental segment and 10 m1 of normal saline FIII
into the control segment. During each period, four three-

minute collections of the venous outflows from both segments

 

were made with three one-minute intervals between them. -
The venous blood was collected in graduated cylinders and, E
after its volume had been recorded, returned to the reservoir.
The last three-minute flow collections from the experimental
segment during the precontrol and test periods were used for
the measurement of osmolality. Osmolality was determined
by the technique of freezing point depression with an osmo-
meter (Advanced Instruments, Inc., Model 67—31LAS, Newton
Highlands, Mass.). After each period, the luminal contents
of each segment were removed and the volume measured with a
syringe. The lumen of each segment was then gently washed
with normal saline.

Using the experimental protocol described above
the effects of any three or all four of the digested food
mixtures were examined in a random sequence in a given
double segment preparation. The two segments were alter-
nately used as experimental and control segments. After

each animal had been sacrificed, the two jejunal segments

45

were dissected clear of mesentery and weighed on a tOp
loading precision balance (Mettler, Model P1200, Hightown,
NJ).

Expression of Data and
Statistical Methods

 

The data obtained from the experiments in which
blood flows through the superior mesenteric artery and an
isolated jejunal segment were simultaneously measured were
expressed in percent of control values. Student's t-test
modified for paired comparisons (49) was used in the
statistical analysis of the results.

In the experiments done with the double jejunal
segment preparation, all of the blood flow data were ex-
pressed as ml/min/lOO grams of the intestinal tissue. The
blood flow data of the last three-minute flow collections
in each period were considered the most representative of
that period and used in the statistical analysis. Resis-
tances were calculated and expressed as mm Hg/ml/min/lOO gm
of intestinal tissue. The resistance data were tabulated
in an identical manner as the blood flow data. The luminal
pressure data were separated into two components: 1) basal
luminal pressure and 2) phasic luminal pressure. The value

of the basal luminal pressure was the average of the lowest

point of all the pressure waves occurring during each period.

' "3.. 3.31.130?“ '~ A o

 

46

The value of phasic luminal pressure was the average of
the amount of vertical spread of all the pressure waves
(i.e., the difference between peak pressure and basal

pressure) occurring during each period. The basal and
phasic luminal pressures recorded during the last three Tr”?
three-minute flow collections of each period were then

averaged and expressed in mm Hg. The blood flow, resis-

tance and pressure values of the first three-minute flow

 

collection period were omitted from tabulation because in
some experiments these values were apparently influenced

by distention of the lumen after the introduction of fluids.
The influence, however, normally lasted only two minutes.
Changes in the volume of the placed fluids over a fifteen
minute stay in the lumen were obtained by taking the dif-
ference between the volume of fluid introduced and removed
from the jejunal lumen during each period. All of the data
(blood flow, resistance, changes in the volumes of the
placed fluids, basal and phasic luminal pressures, and
venous osmolality) were compared from one period to the
next with Student's t-test modified for paired comparisons
(49). Concurrent changes in blood flow and resistance from
precontrol to experimental periods in both segments were
also calculated as percent changes from precontrol. The
changes that occurred in the experimental segment were

then compared to the concomitant changes occurring in the

47

control segment with Student's t—test modified for paired
comparisons (49). Furthermore, an analysis of variance,
single classification (49), was used to compare the relative
effects of the four different food mixtures on blood flow

and resistance.

 

CHAPTER IV

RESULTS

The results of the first and second series of
experiments in which blood flows were simultaneously
measured through the superior mesenteric artery (SMA)

and a segment of the jejunum are shown in Figure 1. In

 

the first series (TOp, Figure l) digested food was per- a
fused through the duodenal-jejunal portion of the intes-
tine while the isolated jejunal segment contained the
control PEG solution. In the second series (Bottom,
Figure 1) digested food was placed in the isolated jejunal
segment while the rest of the small intestine remained
intact. The average systemic arterial pressure was not
significantly altered throughout either series of experi-
ments.

As shown in the top panel of Figure 1, blood
flow through the SMA significantly increased to 113 percent
of its control flow within ten minutes after the start of
the perfusion. By twenty minutes after the start of the
perfusion, SMA flow increased to 123 percent of control and

was maintained at this level for the remainder of the hour.

48

 

TOP:

BOTTOM:

49

FIGURE 1

Blood flow, as percent of control, of the superior
mesenteric artery (SMA) and the isolated jejunal
segment during infusion of digested food into the
duodenum at 4 cc/min. The control flow in SMA =

258 1 21 ml/min; the control flow in the isolated
jejunal segment = 0.06 i 0.05 ml/min/gm (mean : S.E.)
(N = 6).

*Denotes that the value is statistically different

from control at p < 0.05.

Blood flow, as percent of the control, of the superior
mesenteric artery (SMA) and the isolated jejunal
segment prior to and after luminal placement of
digested food into the jejunal segment. The control
flow in the SMA = 227 i 19 ml/min; the control flow

in the isolated jejunal segment = 0.45 i 0.03 ml/min/gm
(mean : S.E.) (N = 10).

*Denotes that the value is statistically different

from controls at p < 0.05.

Blood Flow?! of Control

Blood Flow '10 of Control

 

 

 

I30 1:
N=6 1* 1* In: I L 1*
'2” W" SMA
T/
‘1
no I /
‘l
I’ .
m A . l Je|unum rrfl
./
I“ I 1 1 .
.. 1 . 1
Food In Duodenum
0 10 20 30 40 50 60

Time (min)

150
N =10

I40 /
Jeiun um /I 1*

130 *-

m /Lr

 

Food in Jeiunum

 

'3 i 4 0 4 I 12 13
Time (min)

51

The venous outflow from the isolated jejunal segment, which
had no contact with food, did not significantly change from
its control value throughout the perfusion period. The
average systemic arterial pressure was 126 mm Hg.

The luminal placement of undiluted digested food -rean
into the isolated jejunal segment, on the other hand, in-

creased the venous outflow of this segment but did not alter

‘ ' T’n-tHA'Jfiié 'A a. 2'

SMA flow (Bottom, Figure 1). The venous outflow from the

 

 

isolated jejunal segment significantly increased to 119 per-

 

cent of its control value by the sixth minute, and reached
a maximum, 140 percent of control, at fifteen minutes after
the intraluminal placement of food. The average systemic
arterial pressure was 128 mm Hg.

The results of the experiments performed on the
double segment preparation are shown in Tables 1-5. Tables
1 and 2 show the effects of intraluminal placement of one
of the four digested food preparations (1:0, 1:2, 1:4, or
1:9 Food) in one segment and normal saline in the other
segment on the venous outflows (Table l) and calculated
vascular resistances (Table 2) of the two segments. The
luminal placement of undiluted food (1:0 Food), 1:2 Food
or 1:4 Food increased the venous outflow and decreased the
vascular resistance of the segment containing food (Tables
1 and 2). The venous outflow and vascular resistance of

the control segments containing normal saline were not

52

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53

 

 

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54

significantly altered from control values when food was
in the experimental segments (Tables 1 and 2).

The luminal presence of 1:9 Food increased the
average venous outflow and decreased the average vascular
resistance of the jejunal segment (Tables 1 and 2). These
changes, however, were not statistically significant. In
five of the seven animals the luminal placement of 1:9
Food increased the flow and decreased the resistance, but
in the other two animals there was a decrease in flow and

an increase in resistance. Since these changes in the

latter two dogs were associated with a decrease in systemic

arterial pressure, the increased resistance may be due to
an increase in sympathetic activity as a result of the de-

crease in the systemic pressure. This is supported by the

finding that the flow and resistance of the control segment

in these two animals also decreased and increased, respec-
tively. In the other five animals the flow and resistance
of the control segment or the systemic pressure did not
significantly change. The average flow and resistance of
the control segment in all these seven animals did not
significantly change from one period to the next (Tables
1 and 2).

Table 3 shows the percent change in blood flow and

vascular resistance from the precontrol value while one of

the four food mixtures was in one segment and normal saline

lkainnv'm‘ —n.1

 

 

 

 

55

in the other segment of the double segment preparation.

Only the 1:9 Food in the lumen did not significantly alter
jejunal blood flow and resistance when the values obtained
during the test period were compared to the precontrol

values. Since both segments were subjected to the same .0__0.
systemic influences (i.e., blood pressure, systemic nerve
activity, etc.) at a given time, any difference in the (
vascular responses of the two segments can be reasonably '

attributed to the differences in their luminal contents (21).

 

The changes that occurred from the precontrol to the test
periods in the experimental segment were, therefore, compared
to those occurring in the control segment (last column, Table
3). This comparison shows that the luminal placement of any
of the four digested food mixtures, including the 1:9 Food,
significantly increased the venous outflow and decreased the
vascular resistance. The data of the last column of Table 3
were also analyzed by an analysis of variance (single classi—
fication) to see if the four food mixtures used in this
study produced different effects. The analysis showed that
their effects on flow and resistance were not statistically
different from one another at a p value less than 0.05.

Table 4 shows the mean basal and phasic luminal
pressures of the jejunal segments while either normal saline
or any of the digested food mixtures was in the lumen. The

presence of undiluted food in the lumen increased the mean

 

56

 

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57

basal luminal pressure of the jejunal segment. The mean
phasic luminal pressure was also increased when undiluted
food was in the lumen. The increase in phasic pressure,
however, was not statistically significant. In five of

the six animals the phasic luminal pressure was increased,

whereas, in the other animal it was slightly decreased.
The luminal placement of 1:2, 1:4, or 1:9 Food did not
change the mean basal or phasic luminal pressure of the

jejunal segment from those observed during either control

 

period. The mean basal and phasic luminal pressures of
the control segments containing normal saline did not
change throughout the three periods.

Table 5 shows the effects of luminal placement of
any of the four digested food mixtures or normal saline on
the venous osmolality and changes in the volumes of the
placed substances. In either segment the volume of normal
saline in the lumen tended to decrease (ranges: 0.3 ml-
l.7 ml) over a fifteen minute period. In contrast, un-
diluted food increased its volume by an average of 2.5 ml
over a fifteen minute stay in the lumen. The undiluted
food also significantly increased the venous osmolality
by an average of 10.6 mOsm/kg above the precontrol value.
The 1:2 and 1:4 diluted foods lost their volume while in
the lumen, but these losses were not different from those

observed while normal saline was in the lumen. While the

 

58

. JD

 

 

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.0 00000

59

1:9 diluted food was in the lumen it lost a greater amount
of volume than did normal saline. The luminal presence of
1:2, 1:4, or 1:9 Food did not significantly change the
venous osmolality observed while normal saline was in the
lumen.

Table 6 shows the osmolalities of the supernatants
of centrifuged undiluted or diluted digested foods. The
osmolality of a supernatant obtained from a food mixture
prepared from any one can of dog food progressively decreased
with each greater dilution. In four of ten cases a super-
natant could not be obtained from the undiluted digested

food mixture after centrifugation.

 

 

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61

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CHAPTER V

DISCUSSION

.*__:.__ .

The blood flow through the superior mesenteric
artery increases (7, 8, 29, 30, 37, 54-56) and the resistance
of this vascular bed decreases (29, 30, 54-56) after a meal

in unanesthetized dogs. The increased superior mesenteric r

 

artery blood flow during digestion and absorption of a meal i
has been prOposed to be a result of a redistribution of the
cardiac output at the expense of blood flow to the extreme-
ties (29, 30, 54-56). Furthermore, the studies performed on
anesthetized dogs suggest that the postprandial intestinal
hyperemia is not generalized, but is localized only to that
portion of the intestine directly in contact with food or
glucose (15, 21, 23, 52, 57). The present study was designed
to further evaluate the supposition that the intestinal
hyperemia due to the luminal presence of food is a local
phenomenon. The present study also assessed whether or not
and to what degree the local hyperemia could be influenced

by the concentration and/or osmolality of the food and in-
testinal motility. To accomplish these aims two different
surgical preparations of the canine small intestine were

used.

62

63

In one preparation blood flows through the superior
mesenteric artery and an isolated jejunal segment were
simultaneously measured. Two series of experiments were
performed with this preparation. In one series the lumen
of the duodenal-jejunal portion of the small intestine (60-
70 cm in length) was perfused with digested food, while the
isolated segment (lo-12 cm in length and immediately distal
to the perfused site) was not allowed to have contact with

food. In another series digested food was placed in the

 

lumen of the isolated segment while the duodenal-jejunal
portion of the small intestine was left intact.

In the second preparation the venous outflows from
two isolated adjacent jejunal segments (10-12 cm in length)
were simultaneously measured while one segment contained one
of the four different concentrations of digested food and
the other segment contained normal saline. The osmolality
of the venous outflow, changes in the volumes of the lumin-
ally placed food, and basal and phasic luminal pressures of
the segments were also measured.

As shown in the tOp panel of Figure l, perfusion
of the duodenal-jejunal portion of the small intestine with
food increased the blood flow through the superior mesenteric
artery (SMA), but did not significantly alter the flow
through the isolated segment having no contact with the food.

On the other hand, as shown in the bottom panel of Figure l,

 

64

the placement of digested food into the lumen of the
isolated segment increased the flow through this segment,
but did not significantly alter the flow through the SMA.
Since the isolated segment was perfused by the SMA, the
increased flow through this segment should have been accom—
panied by a simultaneous increase in flow through the SMA
as measured with the electromagnetic flowmeter. The absence
of a significant change in SMA flow is most probably due to
the sensitivity of the flowmeter. The maximum increase in
the venous outflow from the isolated segment ranged from
1.6 to 10.3 ml/min, which would represent an increase in
SMA flow of l to 5 percent above the control level. Since
a 5-10 percent experimental error is involved in measuring
flow with an electromagnetic flowmeter, a change of this
magnitude in SMA flow may not have been detected by the
flowmeter. Furthermore, had this change been detected by
the flowmeter, a change in flow of 1-10 ml/min would have
represented a barely noticeable change of 0.1 to 1 mm in
the recorded tracings.

Since the systemic arterial pressure remained un-
altered throughout both series of experiments, the increase
in blood flow through the SMA or the isolated segment was
due to a decrease in their respective vascular resistances.
These two series of experiments indicate that the post-

prandial intestinal hyperemia is a local phenomenon occurring

 

65

only in the area exposed to chyme. This supposition is
further supported by the results obtained from the experi-
ments performed on the double segment preparation. Luminal
placement of undiluted, 1:2 or 1:4 diluted digested food
into one of the two segments increased the flow and decreased _ nua—1
the vascular resistance of that segment, but did not alter
the flow and vascular resistance of the adjacent segment
containing normal saline (Tables 1 and 2). These studies

thus confirm previous reports which suggested that the post-

 

prandial intestinal hyperemia is localized to that section
of the small intestine in contact with food (23, 57).

The peak increases in SMA blood flow observed in
this study ranged from 20 to 47 percent above the control
and occurred fifteen to thirty-five minutes after the start
of intraduodenal perfusion with digested food. The magnitude
of the increased flows are comparable to those found by other
investigators using flowmeters to measure SMA flow in con-
scious dogs after oral feeding. The mean peak increases in
SMA flow during digestion of a meal were found to be 28 per-
cent (30), 33 percent (29), 71 percent (7, 8), and 132 per-
cent (54-56) above prefeeding levels and occurred fifty to
sixty minutes after the ingestion of a meal. The peak flow,
however, appeared earlier in the present study than in the

studies on conscious dogs. This difference is probably due

66

to the direct infusion of digested food into the small
intestine in the present study as compared to the oral
ingestion of food in the other studies. When food is
ingested orally, the rate of entrance of the food into the

small intestine is regulated by the rate of gastric empty-

11“]
2;
. L

ing. In chloralose-urethane anesthetized.dogs,Chou et al.

(23) noted a maximum increase in SMA flow of 52 percent at

 

sixty minutes after the start of the infusion of digested

food into the duodenum at 4 cc/min. As compared to their
study, the appearance of peak SMA flow is sooner and its
magnitude is less in the present study. The reason for
these differences is unclear for the surgical preparation
and experimental protocol were similar.

The effect of luminal placement of food on compart-
mental blood flow of the jejunal wall has been studied by
Yu §E_gl. (57). They used the radioactive microsphere method
to measure blood flow to three adjacent jejunal segments.
One segment was left intact and the other two segments con-
tained either undiluted digested food or isotonic PEG.
Total wall blood flow to the segment containing food was in-
creased by 47.5 percent as compared to the flow to the seg- l
ment containing PEG. This is in close agreement with the
46 percent increase in flow to the segment containing food
as compared to the flow to the control segment noted in the

present study (Table 3, last column). Furthermore, in the

 

67

study by Yu §£_gl., the increased jejunal blood flow was
due primarily to an increase in flow to the mucosal layer.
Since the hyperemia occurred in the mucosal layer, which
is in direct contact with food and performs digestive and
absorptive functions, their study offers further support 5m.m.
to the hypothesis that the postprandial intestinal hyper-
emia is a local phenomenon.

The second aim of the present study was to examine

whether or not and how much the concentration and/or tonic-

 

ity of food affect the magnitude of the local postprandial
intestinal hyperemia. The double segment preparation was
used for this study. The concentration of the digested
food was altered by adding two, four, or nine parts of dis-
tilled water to one part of the digested food. Since the
osmolality of these food mixtures is difficult to determine
directly by the freezing point depression technique, the
food mixtures were centrifuged and the osmolalities of the
supernatants were measured. As shown in Table 6, the os-
molalities of the supernatants of the digested foods de-
creased with each greater dilution. The data presented in
Table 6 suggest that undiluted food is hypertonic (ranging
from 700-1700 mOsm/kg), the 1:2 diluted food is near iso-
tonic (with 8 of 10 values ranging from 230-370 mOsm/kg),
the 1:4 diluted food is hypotonic (ranging from 125-320

mOsm/kg with 9 of 10 values below 300 mOsm/kg) and the 1:9

68

diluted food is even more hypotonic (ranging from 50-200
mOsm/kg with 9 of 10 values being below 140 mOsm/kg). For
any given food mixture there was some variation in the
osmolality values of the supernatants from one can to the
next. This variability is probably due to a variation in _——~—
the salt, as well as, the water content among different
cans of the commercial dog food. In fact, in some cases, 5
after centrifugation of samples of undiluted digested food

an aqueous layer was not present in sufficient amounts to

 

obtain a supernatant. In addition, refrigeration (24 hours)
of the homogenized dog food prior to digestion and prepara-
tion of the food mixtures had varied effects on the osmolali-
ties of the supernatants. As mentioned previously (Chapter
II, Methods and Procedures) four cans of dog food were homog-
enized and the homogenate of each can was divided into two
halves. One half was digested and centrifuged that day; and
the other half was refrigerated for twenty-four hours, and
digested and centrifuged the following day. As shown in
Table 6, in half of the cases the osmolalities of the super—
natants were lower after refrigeration (cans l and 4) and

in the other half of the cases the osmolalities were greater
after refrigeration (cans 2 and 3). This variability must

be largely due to the experimental error involved in dividing
the homogenate into two halves. Indeed, if two samples were

obtained from one can (can 5, Table 6) and treated

69

simultaneously the osmolality values of the two samples
were similar. It appears, therefore, that the osmolality
of these digested food mixtures can not be accurately
determined in_zi££g.

The osmolality might change in the lumen as a result

‘5
b
l

of further digestion of the food mixtures in the lumen,
probably at the brush border of the mucosal cells. Thus,

the apparent osmolality of these food mixtures in the lumen i

 

were estimated from changes in the volume placed in the

lumen and the local venous osmolality. Chou et_gl. (21)

have quantitatively examined the effects of luminal place-
ment of glucose or polyethylene glycol solutions of known
osmolality (150-3000 mOsm/kg) on the local venous osmolality
and net transmucosal movement of fluid. Hypertonic solutions
having osmolalities of 1,200 and 3,000 mOsm/kg increased the
venous osmolality by about 11.5 and 15.8 mOsm/kg and in-
creased the lumen volume by about 3.3 and 7.7 ml, respectively.
Isotonic solutions having an osmolality of 300 mOsm/kg did

not alter the venous osmolality and decreased the lumen

volume by about 1.0 m1. Hypotonic solutions having osmolali-
ties of 150 mOsm/kg did not alter the venous osmolality and
decreased the lumen volume by about 4 ml. Since the osmolali-
ties of these solutions can be accurately determined by an
osmometer and the solutions are not digested in the intes-

tinal lumen, the quantitative changes in venous osmolality

70

and lumen volume observed in that study can be used as a
reference for the osmolality of the digested food in the
lumen in this present study.

As shown in Table 5, the luminal placement of un-
diluted digested food increased the local venous osmolality
by 10.6 mOsm/kg and the volume of the placed food by 2.5 ml.
These changes are qualitatively similar to those observed
while a hypertonic solution of glucose or PEG of 1200 mOsm/kg
was in the lumen (21). The osmolality of the undiluted
digested food in the lumen therefore, is near 1200 mOsm/kg.
This value agrees fairly well with the osmolality of the
supernatant of the undiluted digested food (1100 mOsm/kg).
The luminal placement of 1:2 and 1:4 diluted food did not
alter the venous osmolality and decreased the volume of the
placed food by 0.7 and 1.1 ml, respectively. Also, the loss
in volume of the placed 1:2 or 1:4 diluted food was not sig-
nificantly different from the loss in volume of the placed
normal saline (1.0). The magnitude of the changes in lumen
volume are also quantitatively similar to those observed
while an isotonic solution of PEG (300 mOsm/kg) was in the
lumen (21). These comparisons indicate that, in the lumen,
the osmolality of the 1:2 or 1:4 diluted food is near iso-
tonic. As shown in Table 6, the osmolality of the super-
natant of 1:2 Food is near 300 mOsm/kg, but that of 1:4 Food

is much lower than 300 mOsm/kg. In addition to the

 

71

previously discussed experimental error which may be in-
volved in the determination of the osmolality i2_!it£2,
intraluminal digestion of the food mixture might also
contribute to the increased osmolality of 1:4 diluted food
in the lumen. The luminal placement of 1:9 diluted food
did not alter the venous osmolality and decreased the volume
of the placed food by 3.5 ml. The loss in lumen volume
observed while 1:9 diluted food was in the lumen is greater
than the loss in volume of the placed normal saline. Thus
the 1:9 diluted food is probably hypotonic in the lumen.
The osmolality of the supernatant of 1:9 diluted food de-
termined in_yi££9_also indicates that this food mixture is
hypotonic. Physiologically, the chyme entering the jejunum
is nearly isotonic. The food mixtures used in this study
clearly included the physiological range of the concentra-
tions and/or tonicity of the chyme entering the proximal
jejunum.

As can be seen in Tables 1 and 2, the luminal place-
ment of undiluted food, 1:2 diluted food, or 1:4 diluted
food increased the venous outflow and decreased the vascular
resistance of the jejunal segments. The luminal placement
of 1:9 diluted food did not significantly alter the flow or
resistance. The lack of significant changes in flow and
resistance in the case of the 1:9 diluted food is probably

due to an increase in sympathetic stimulation as a result

 

72

of a decrease in systemic arterial pressure in two of the
seven animals. In these two animals the venous outflow
decreased and the vascular resistance increased. In the

other five animals the systemic pressure was not altered

 

and the luminal presence of 1:9 Food increased the venous q_.rj
outflow and decreased the vascular resistance. Table 3

further shows that, as compared to the changes in flow and a

 

resistance occurring in the control segments, the luminal

placement of any of the four food mixtures, including the

 

1:9 diluted food, significantly increased the flow and de-
creased the resistance of the segment containing food. A
statistical analysis using a single classification analysis
of variance indicated that the magnitude of the increased
flow and decreased resistance produced by the luminal place—
ment of any of the four food mixtures were similar. There-
fore, it appears that the concentration and/or tonicity of
the food, over the range used in this study, is not an im—
portant contributing factor in the observed postprandial
intestinal hyperemia. Additional support for this conclusion
is offered by a comparison of the vascular effects of un-
diluted digested food and a hypertonic nonabsorbable sub-
stance. As described above, the 1umina1 placement of un-
diluted food increased the venous osmolality by 10.6 mOsm/kg
and the lumen volume by 2.5 ml (Table 5). These changes are

comparable to the 10.7 mOsm/kg increase in the venous

73

osmolality and 3.0 ml increase in lumen volume observed
when 34 percent PEG solution (1200 mOsm/kg) was in the
lumen (21). The osmolality of the undiluted digested
food in the lumen, therefore, seems to be near that of

the 34 percent PEG solution. While the undiluted digested

-——-?a

food increased the jejunal venous outflow by 39 percent

above the control level, the 34 percent nonabsorbable PEG

nu

solution did not alter the venous outflow. From this

comparison, it appears that the hypertonicity of the un-

 

diluted digested food in the lumen is not an important
factor in the resultant local hyperemia.

In a previous study, Chou et a1. (21) have evaluated
the role played by the tonicity of the lumen contents in the
intestinal hyperemia. Using a double segment preparation,
they found that the venous outflows from the two segments
were increased to the same extent by the luminal placement
of isotonic glucose in one segment and hypotonic glucose in
the other segment. In the same study, they compared the
venous outflows from the two segments while one contained
solutions of hypertonic glucose and the other contained
solutions of polyethylene glycol (PEG) of the same osmolality
(20% glucose = 34% PEG and 50% glucose = 85% PEG). The
luminal placement of hypertonic glucose or PEG of the same
osmolality increased the venous osmolality and the lumen

volume to the same extent. However, while 20 percent and

74

50 percent glucose solutions increased the venous outflow,
the 34 percent PEG solution did not effect the venous out-
flow and the 85 percent PEG solution did not increase the
venous outflow to the same extent as did the 50 percent glu-
cose solution. Polyethylene glycol is a nonabsorbable, fee.
inert substance (48) and does not appear to be vasoactive
(11). Thus, they concluded that in addition to a direct
vascular effect of hypertonicity some other mechanisms are

involved in the increase in intestinal blood flow which 3

 

occurs while hypertonic glucose is in the lumen.

The contractile state of the intestinal wall can
influence intestinal blood blow (2, 13, 14, 27, 34, 35, 46,
47). Elevations in intraluminal pressure or strong tonic
contractions of the intestine compress the intramural vessels
and decrease intestinal blood flow (2, 27, 34, 35, 47). On
the other hand the blood flow through the intestine is aug-
mented by rhythmic contractions or decreases in wall tension
of the gut via a pumping action or an increase in vascular
transmural pressure, respectively (14, 34, 46, 47). As
shown in Table 4, only the luminal presence of undiluted
digested food in a jejunal segment increased the basal and,
in most cases, the phasic luminal pressures of that segment.
The basal luminal pressure is an indication of the intestinal
tonus or tonic contractions while the phasic luminal pressure

is an indication of rhythmic contractions.

75

Sidky and Bean (47) have indicated that the two
types of intestinal contractions (tonic and rhythmic) exert
opposite effects on the local intestinal blood flow. Since
both the basal and phasic pressures were increased by the
undiluted digested food in the present study, the effect of
the former may have nullified the effect of the latter on
the venous outflow from the jejunal segment. Thus, to what
extent the increased motility of the jejunal segment con-
tributed to the local hyperemia caused by the luminal
presence of undiluted digested food is difficult to evaluate.
However, Chou gg_al. (21) have also noted that an increase
in motility of a jejunal segment during the luminal presence of
a hypertonic glucose solution was not strong enough to alter
the venous outflow from that segment. Furthermore, all of
the three diluted food mixtures increased the venous outflow
to an extent similar to that of undiluted food, but did not
significantly alter the basal or phasic luminal pressures.
Thus, it appears that the jejunal motor activity does not
play a major role in the local hyperemia when food is in the

lumen.

 

CHAPTER VI

SUMMARY AND CONCLUSIONS

The blood flow through the superior mesenteric
artery increases postprandially. This hyperemia has been
suggested to be localized to that portion of the intestine
directly in contact with food. In the present study two
different surgical preparations of the canine small intes-
tine were used to evaluate the hypothesis that the intes-
tinal hyperemia is a local phenomenon. In addition, the
influences of the concentration and/or tonicity of the
digested food and intestinal motility on the local hyper-
emia were examined.

In one preparation the blood flows through the
superior mesenteric artery (SMA) and an isolated jejunal
segment were simultaneously measured while digested food
was pumped into the duodenal lumen or placed into the
isolated jejunal segment. In the former experiment the
isolated segment was not allowed to have contact with food;
while in the latter experiment the duodenal-jejunal portion
of the intestine was left intact. In the other preparation
the venous outflows and luminal pressures (basal and phasic)

of two isolated in situ jejunal segments were simultaneously

76

 

77

measured while one segment contained one of the four dif—
ferent concentrations of digested food and the adjacent
segment contained normal saline. The four food mixtures
were: undiluted digested food, and digested food diluted
1:2, 1:4, and 1:9 with distilled water. As an indicator
of the osmolality of the digested food in the lumen the
osmolality of the venous outflow and changes in the volume
of the placed food or normal saline were also measured.
Furthermore, the four digested food mixtures were centri-
fuged and the osmolalities of the supernatants were de-
termined in vitgg.

The results of these studies are summarized as

follows:

1) The following results were obtained from the
study done with the preparation in which the
blood flows through the SMA and an isolated

jejunal segment were simultaneously measured.

a) Perfusion of the duodenal-jejunal portion
of the small intestine with food increased
the SMA blood flow, but did not alter the

flow through the isolated jejunal segment.

b) Placement of food into the isolated jejunal
segment increased the flow through that seg-
ment, but did not significantly alter the

flow through the SMA.

 

78

2) The following results were obtained from the
study done with the preparation in which the
venous outflows from two isolated jejunal

segments were simultaneously measured.

a) Luminal placement of undiluted digested
food, 1:2 or 1:4 diluted digested food in
one segment significantly increased the
flow and decreased the vascular resistance
of that segment without affecting the flow
or resistance of the adjacent segment which

contained normal saline.

b) Intraluminal placement of undiluted or any
of the diluted digested food mixtures in-
creased the venous outflow and decreased the
vascular resistance of the jejunal segment
as compared to the concomitant changes in
flow and resistance occurring in the adjacent

segment containing normal saline.

0) The magnitude of the mean percent peak in-
crease in flow or decrease in vascular
resistance produced by all four food mixtures

were statistically similar.

d) The undiluted digested food increased its

volume over a fifteen minute stay in the lumen.

 

79

Normal saline, 1:2 or 1:4 diluted food
lost similar amounts of their volume
while in the lumen. The 1:9 diluted
food lost a greater amount of volume

than did normal saline. EM‘H

e) Only the luminal placement of undiluted

digested food increased the local venous j

 

osmolality, the basal luminal pressure,

I L‘

and the phasic luminal pressure.

3) The osmolalities of the supernatants of centri-
fuged undiluted, 1:2 diluted, 1:4 diluted, and
1:9 diluted digested foods i2_vi££g were approx-
imately 1100, 331, 203, and 108 mOsm/kg, re-

spectively.

The following conclusions are drawn from these

studies:

1) The increase in intestinal blood flow during the
intraluminal presence of digested food is, in-

deed, a local phenomenon.

2) In vitro, undiluted food is hypertonic, 1:2
diluted food is nearly isotonic, and 1:4 and

1:9 diluted foods are hypotonic.

3)

4)

80

In the lumen, undiluted food is hypertonic,

1:2 and 1:4 diluted foods are nearly isotonic,

and 1:9 diluted food is hypotonic.

The local hyperemia produced by the presence
of digested food in the lumen of the jejunum
is not affected by the concentration and/or

tonicity of the food or the motor activity of

the jejunal wall.

 

lb

 

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