REGIONAL BLOOD FLOW DURING DIGESTION
IN THE CONSCIOUS DOG

By

Robert Henry Gallavan, Jr.

A THESIS

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

MASTER OF SCIENCE

Department of Physiology

1978

ABSTRACT

REGIONAL BLOOD FLOW DURING DIGESTION
IN THE CONSCIOUS DOG

By

Robert Henry Gallavan, Jr.

Blood flows to the major organs of the resting con-
scious dog were measured prior to and thirty and ninety
minutes after feeding using radioactive microspheres.
Cannulae were chronically implanted in the left atrium
(for microsphere injection) and mammary artery (for
reference arterial samples). Blood flow to the heart,
adrenals, adipose tissue, skeletal muscle, brain, stomach
and distal jejunum was unchanged during digestion. The
increase in blood flow in the small intestine spread from
the duodenum and proximal jejunum at thirty minutes to
the ileum ninety minutes after feeding and was confined
to an increase in flow to the mucosal layer of the intes-
tinal wall. Blood flow to the colon was unchanged except
for a decrease in the distal colon at thirty minutes.
Blood flow to the pancreas increased and hepatic artery
flow decreased during digestion. Thus, the cardiovascular
response to feeding is limited to those organs actively

involved in digestion.

To my parents

ii

ACKNOWLEDGEMENTS

I wish to express my gratitude to Dr. C. C. Chou
for his support, guidance, encouragement and patience
during the course of this study. I would like to thank
Dr. J. B. Scott and Dr. R. P. Pittman for their services
on the guidance committee. I would especially like to
thank Peter R. Kvietys, Jenny Shih and Siu Po Sit for the
long and tedious hours they shared with me during the

course of these experiments.

iii

TABLE OF CONTENTS

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

CHAPTER I - INTRODUCTION .
CHAPTER II - LITERATURE REVIEW.
CHAPTER III - METHODS.
Preparation of the Experimental
Animals.
Preparation of the Microspheres.
Experimental Protocol.
Series 1.
Series 2.
Tissue Sampling. .
Calculation of Blood Flow.
Expression of Data and Statistical
Methods.
CHAPTER IV - RESULTS.
CHAPTER V - DISCUSSION
CHAPTER VI - SUMMARY AND CONCLUSIONS.

BIBLIOGRAPHY

iv

Page

vii

12

12
13
14
15
15
18
19
20
39
51

54

Table

10

11

LIST OF TABLES

Mean 1 S.E.M. total and regional blood flow
(ml/min/lOO gm) to the brain in the con-
scious dog before and after feeding . .

Mean 1 S.E.M. total and regional blood flow
(ml/min/lOO gm) to the brain in the con-
scious fasted dog . . . . . . . . . .

Mean 1 S.E.M. blood flow (m1/min/100 gm) to
various organs of the conscious dog before
and after feeding

Mean 1 S.E.M. blood flow (ml/min/lOO gm) to
various organs of the fasted conscious dog.

Mean 1 S.E.M. total and compartmental blood

flow (ml/min/lOO gm) to the wall of the
gastric body in the conscious dog

Mean 1 S.E.M. total and compartmental blood
flow (ml/min/lOO gm) to the wall of the
gastric antrum in the conscious dog

Mean 1 S. E. M. total and compartmental blood
flow (ml/min/lOO gm) to the wall of the
duodenum in the conscious dog

Mean 1 S.E.M. total and compartmental blood
flow (ml/min/lOO gm) to the wall of the
proximal jejunum in the conscious dog

Mean 1 S.E.M. total and compartmental blood
flow (ml/min/IOO gm) to the wall of the
distal jejunum in the conscious dog .

Mean +S. E. M. total and compartmental blood
flow (ml/min/lOO gm) to the wall of the
ileum in the conscious dog. . . .

Mean 1 S.E.M. total and compartmental blood
flow (ml/min/lOO gm) to the wall of the
proximal colon in the conscious dog . . . .

Page

21

22

24

26

27

28

31

33

34

36

37

Table Page

12 Mean i S.E.M. total and compartmental blood
flow (ml/min/IOO gm) to the wall of the
distal colon in the conscious dog . . . . . . 38

vi

LIST OF FIGURES

Figure Page
1 The effects of histamine on the total and
regional blood flow (m1/min/100 gm) to the

wall of the gastric body and antrum . . . . . 30

vii

CHAPTER I
INTRODUCTION

Early studies of the postprandial cardiovascular
response in conscious animals indicated that cardiac
output increased significantly during digestion and
resulted in an increase in blood flow to all organs of
the body. As methodology improved, however, it became
apparent that feeding elicits a biphasic cardiovascular
response. During the presentation and ingestion of food,
cardiac output, heart rate, aortic pressure and resistance
in the various vascular beds are altered in a pattern
which mimics an increase in sympathetic neural activity.
Within five to thirty minutes following a meal, cardiac
output, heart rate, aortic pressure and blood flow to the
heart and kidney return to control levels while superior
mesenteric artery flow starts to rise and reaches a maxi-
mum in thirty to ninety minutes. Blood flow to the limbs
decreases during digestion in the resting animal while
hepatic artery flow remains constant.

Due to the physical limitations of electromagnetic
flowmeters, it has not been possible to measure either
total or regional blood flow to a number of major organs.

The development of the radioactive microsphere technique

2
for measuring regional blood flow has resolved this diffi-
culty. It was the purpose of this study to utilize the
radioactive microsphere technique to measure 1) blood
flow to the brain, pancreas, adipose tissue, and adrenal
glands and 2) regional distribution of blood flow within
the brain, stomach, small intestine and large intestine

in the conscious dog during digestion.

CHAPTER II
LITERATURE REVIEW

Although it had long been assumed that blood flow
to the digestive organs increased during digestion, evi-
dence in support of this hypothesis was not produced
until 1910. At that time Brodie et al. (9) utilized the
oncometric method (a modification of the plethysmographic
method) to study blood flow through an isolated intes-
tinal loop. They demonstrated that the luminal placement
of salt solutions producing either an absorption of salt
and water or an exsorption of fluid produced an increase
in intestinal blood flow. In a further study that year,
Brodie et a1. (10) showed that the presence of Witte's
peptone solution also produced a sustained increase in
intestinal blood flow.

During the period 1924 to 1935, several authors
studied cardiac output in humans after ingestion of a
meal using a gas equilibration method based on the Pick
principle (17,28,32,59). These studies reported a post-
prandial increase in cardiac output which varied in degree
and duration with the size of the meal. An increase in
pulse rate was also noted and in one report systemic

arterial pressure was monitored and found to remain

4
unchanged (32). In his 1929 study, Grollman suggested
that during digestion the splanchnic vasculature dilates
and this increase in flow is compensated by the increased
cardiac output without altering systemic arterial pres-
sure (32).

The first attempts to measure regional blood flow in
conscious dogs during digestion were conducted with thermo-
stromuhr flowmeters (24,34,35). These experiments seemed
to indicate that blood flow in the superior mesenteric,
femoral, common carotid and left circumflex coronary
arteries as well as the hepatic and exterior jugular veins
increased during digestion. In 1940, however, Gregg et
a1. (30) demonstrated that the thermostromuhr was capable
of producing qualitative as well as quantitative errors
in measurement and the technique was subsequently abandoned.

In 1941, Abramson and Fierst (1) examined the peripheral
circulatory response to digestion using the venous occlu-
sion plethysmographic method on the hand, forearm and leg.
The authors noted that peripheral blood flow did not change
following a carbohydrate meal but that blood flow to the
extremities did increase within sixty to ninety minutes
of ingestion of a protein meal.

In 1950, Berman et a1. (5) and Paine and Shock (53)
used the balistocardiograph technique for measuring cardiac
output and reported an increase in cardiac output and
heart rate after a meal. Brandt et a1. (7) used the
bromsulphalein (BSP) clearance method for estimating

splanchnic blood flow in 1955 and reported a 35 percent

5
increase in flow following a protein meal and an 8 percent
decrease in flow following a glucose meal. In 1960,
Reinenger and Nutik (55) used the BSP clearance technique
to show a 25 percent increase in splanchnic blood flow in
humans following a glucose meal. Arterial blood pressure
remained constant throughout the experiment.

Thus most of the studies up through 1960 indicated
that splanchnic blood flow increases postprandially in
humans (8,14) and dogs (9,10,55) and that cardiac output
increases an average of 25 to 45 percent in both species
(S,l7,28,32,34,53,55,59). Furthermore, the composition
of the meal consumed seemed to determine the extent of
the increase in splanchnic flow (8) as well as the degree
and duration of the increase in cardiac output (17,32,55).
Splanchnic blood flow seemed to increase more after a heavy
meal than a light meal and the increase in cardiac output
was greater and of longer duration after a heavy meal.
Arterial pressure remained constant (14,32) and heart
rate increased after the ingestion of a meal (5,17,32).
Blood flow to the arms and legs was also believed to
increase postprandially (1).

With the development of electromagnetic and pulsed
ultrasonic flowmeters, researchers in this field began to
find major discrepancies between their studies and the
less direct methods of previous authors. The first of
such reports came in 1961 when Rushmer et a1. (57) moni-
tored blood flow in the abdominal aorta, renal artery,

superior mesenteric artery and hepatogastric artery of

6
conscious dogs with pulsed ultrasonic flowmeters. Follow-
ing consumption of a plate of commercial dog food, they
noted "a questionable reduction" of blood flow through
the renal artery and abdominal aorta. During the experi-
ment, superior mesenteric artery blood flow did not change
and hepatogastric artery flow increased in only one
instance.

In 1965, Jones et a1. (38) studied the effects of
digestion on cardiac output in humans as measured by the
dye dilution technique (indocyanine green). Contrary to
previous reports, they found no increase in cardiac out-
put twenty minutes after the ingestion of a mixed meal
(30 percent protein, 30 percent fat, 40 percent carbo—
hydrate). This study was contradicted in 1966 by Dagenais
et a1. (19) using the same technique (dye dilution with
Coomassie blue dye) to measure cardiac output in humans
following a protein or carbohydrate rich meal. They found
that both meals caused an increase in cardiac output,
heart rate and systolic pressure which reached a peak
between 180 and 270 minutes after ingestion. It should
be noted that cardiac output also increased in a fasted
control group but the increase in the fed group was sig-
nificantly greater than that in the control group.

Burns and Schenk conducted two studies in conscious
dogs between 1967 and 1969 (12,13) with electromagnetic
flow transducers attached to the superior mesenteric
artery and ascending aorta. They reported that a meal

consisting of 15 ounces of horsemeat produced no change

7
in cardiac output while superior mesenteric artery blood
flow increased within five minutes of feeding and reached
a plateau fifty minutes later. The average increase in
superior mesenteric artery blood flow was 71 percent and
represented an increase in flow to that region from 7.5
to 14.6 percent of cardiac output.

In 1968, Fronek and Stahlgren (27) used electromag-
netic flow transducers in a comprehensive study of the
cardiovascular response to the presentation, ingestion and
digestion of food. Cardiac output and blood flow through
the brachiocephalic, external iliac and superior mesen—
teric arteries were measured in conscious dogs during each
phase of feeding. Systemic pressure and heart rate were
also monitored. When food was first presented, all
measured variables increased with the exception of superior
mesenteric artery blood flow, which remained unchanged.
During ingestion, cardiac output, systemic pressure and
heart rate continued to increase and reached a maximum
within the first minute. Also during the first few
minutes of ingestion, blood flow through the brachio-
cephalic artery continued to increase and external iliac
artery flow decreased. Within one hour of feeding, cardiac
output, systemic pressure and brachiocephalic and external
iliac artery blood flow returned to control levels. Heart
rate remained slightly elevated and superior mesenteric
artery blood flow reached a plateau of 133 percent of
control levels. During the third hour of digestion,

cardiac output, heart rate, systemic blood pressure and

8

external iliac artery blood flow remained at control
levels. Superior mesenteric artery blood flow remained
elevated but brachiocephalic artery blood flow decreased
to 80 percent of control. The authors suggested that the
observed responses to presentation and ingestion of food
could be attributed to a generalized sympathetic response
and that the pattern of blood flow during digestion indi-
cated a redistribution of blood flow in favor of the
splanchnic region at the expense of the extremities.

In that same year, HOpkinson and Schenk (37) studied
postprandial blood flow in the portal vein, hepatic
artery and hepatic vein in conscious dogs with electro-
magnetic flowmeters. They reported a mean hepatic blood
flow of 21.8 ml/min/kg of which approximately 64 percent
was provided by the portal vein. During digestion,
hepatic artery flow remained unchanged (7.7 ml/min/kg)
while portal venous flow increased 76 percent resulting
in an overall increase in hepatic blood flow of 32 percent.
They also reported that cardiac output, as measured by
electromagnetic flowmeter, remained unchanged during
digestion.

In 1969, Vatner et a1. (62) reported findings similar
to those of Fronek and Stahlgren (27) using both electro-
magnetic and pulsed ultrasonic flowmeters. As before,
they found indications of a generalized sympathetic
response to anticipation and ingestion. During digestion,
they noted a decrease in iliac artery blood flow of

approximately 20 percent and an increase in superior

9

mesenteric artery blood flow of as much as 300 percent.
The decrease in iliac artery blood flow, however, lasted
only one hour and was eliminated or reversed if the animal
changed position or walked about. Renal artery blood
flow did not change. In a subsequent study in 1970,
Vatner et a1. (63) demonstrated that the circulatory
responses to anticipation and ingestion were indeed
related to sympathetic activity by attenuating the response
with both alpha-adrenergic and beta-adrenergic blockade.
Neither blockade was effective in eliminating the mesen-
teric vasodilation during digestion, however, and although
cholinergic blockade could eliminate the mesenteric
response, a bilateral vagotomy could not. The authors
also demonstrated a cephalic phase of digestion by placing
food before a muzzled dog and observing a cardiovascular
response similar to that in the fed animals, although it
was less pronounced and the mesenteric vasodilation
lasted only fifteen minutes.

In two additional studies, in 1970 and 1974, Vatner
et al. used the same techniques as in their earlier studies
(62,63) to extend their work to the baboon (65) and the
left circumflex artery of the d0g (64). The results of
these studies are much the same as their previous reports
with the added observation that left circumflex coronary
flow increased during the anticipation and ingestion phases
of feeding but returned to control levels within fifteen

to twenty minutes.

10

In 1975, Norryd et a1. (50) studied cardiac output,
pulse rate, systemic arterial pressure, superior mesen-
teric blood flow and portal venous pressure in the human
using a dye dilution technique. All measurements were
taken three to four times within one hour of feeding.

The authors reported no change in cardiac output, pulse
rate or systemic arterial pressure. Portal venous pres-
sure increased 15 percent above control and superior
mesenteric blood flow increased on the average by 113
percent. Administration of a barium solution with the
meal followed by a fluorosc0pic examination showed that
some food had reached the upper part of the jejunum within
5 minutes of completion of the meal.

In 1976, Chou et a1. (16) used electromagnetic flow-
meters to study blood flow through the celiac and superior
mesenteric arteries in anesthetized dogs in response to
intragastric and intraduodenal placement of digested food.
The results of these experiments suggested that blood flow
increases only in those portions of the small intestine
exposed to digested food. These findings were supported
by previous studies by Van Heerden et al. (61) in 1968 and
Yu et a1. (67) in 1975 in which the authors used radioactive
microspheres in anesthetized dogs to study blood flow to
isolated 100ps of the small intestine exposed to hypertonic
glucose solutions. Both studies demonstrated that blood
flow increased significantly in those regions exposed to

hypertonic glucose while flow in other regions did not.

11

In their 1976 study, Chou et a1. (16) used the venous
outflow and radioactive microsphere techniques to examine
total and compartmental blood flow to the wall of an iso-
lated jejunal loop exposed to digested food. The authors
reported that the increase in total blood flow to the
wall of the small intestine was due solely to an increase
in flow to the mucosal layer while blood flow to the sub-
mucosa and muscularis remained unchanged. In 1975, Yu
et a1. (67) had also reported that the increase in blood
flow to the intestinal wall in response to hypertonic
glucose was confined to the mucosal layer while flow to
the submucosa and muscularis remained constant. In 1976,
however, Bond and Levitt (6) reported that blood flow to
all portions of the intestinal wall increased during
digestion in the conscious dog as measured with the radio-
active microsphere technique.

Thus it can be seen that the current concept of the
circulatory response to feeding is that, with the excep—
tion of a brief anticipatory phase, cardiac output, systemic
arterial pressure and blood flow to the heart and kidneys
remain unchanged. Blood flow to the small intestine rises
rapidly, increasing on the average 28-132 percent following
a meal, and may be compensated by a decrease in blood flow
to the extremities. However, at present there are no clear
data concerning the effects of digestion on blood flow to
the brain, pancreas, adipose tissue, adrenal glands,

stomach, small intestine or colon in the conscious dog.

CHAPTER III
METHODS

Preparation of the Experimental Animals

 

Adult mongrel dogs of either sex weighing between 22
and 30 kilograms were anesthetized with sodium pentobar-
bital (30 mg/kg) and ventilated with room air via an
endotracheal tube with a positive pressure respiration
pump (Harvard, Model 607, Dover, Massachusetts). The
left chest was opened under aseptic conditions at the
third intercostal space and an incision was made in the
pericardium in the vicinity of the left atrium. The
left atrium was cannulated via the left atrial appendage
with biologically inert silastic tubing (Dow Corning,
Midland, Michigan; i.d. = 0.078 in, o.d. = 0.125 in) for
the injection of microspheres. The left mammary artery
was also cannulated with the same silastic tubing for the
withdrawal of a reference arterial blood sample and the
monitoring of systemic arterial blood pressure and heart
rate. Both tubings were filled with sodium heparin (1000
units/m1) and exteriorized at the back of the neck. The
surgical incisions were closed, the lungs were reinflated
and the animal was allowed to recover from surgery and
anesthesia. Meperidine hydrochloride (40 mg) was adminis-
tered intramuscularly immediately following surgery and

12

13
again six hours later. Procaine penicillin (400,000
units) and dihydrostreptomycin (0.5 gm) were administered
intramuscularly prior to surgery and twice a day for a
few days.

The animals were allowed food and water ad Zibitum
after surgery and were exercised daily. They were exposed
to the laboratory setting for at least one hour each day
during which time the cannulas were flushed and refilled
with heparin. This was done to insure the patency of the
cannulas and to accustom the animal to the experimental

environment in order to minimize stress.

Preparation of the Microspheres

 

Carbonized microspheres labeled with either
scandium-46 (dia = 13.2 1 0.7 p), strontium-85 (dia =
13.6 1 0.9 u) or cerium-141 (dia = 13.9 1 1.0 u) were
obtained from the Nuclear Product Division of the Minnesota
Mining and Manufacturing Company (3M Center, St. Paul,
Minnesota). The specific activity was 10 millicuries/gm
and the specific gravity was 1.23 1 0.05 gm/cc. One
milligram of microspheres contained approximately 440,000
microspheres. The microspheres were delivered in a solu-
tion of 10% dextran and 0.05% Tween 80 (polyoxyethylene
sorbitan mono-oleate) to prevent aggregation of the spheres.
The microsphere suspensions to be used during the experi-
ments were prepared from the stock solution a few minutes
prior to use. An appropriate volume of agitated stock

solution containing approximately 2.5 x 106 microspheres

14
(0.6 to 0.8 ml) was added to 2 ml of a 20% dextran solu-
tion in a glass centrifuge tube and the whole was treated
with an ultrasonic sonifier cell disruptor (Branson
Instrument Co., Long Island, New York) to achieve a
uniform dispersion of the microspheres. This solution
was then drawn into a 3 ml plastic disposable syringe for
injection. The order of injection of the microspheres

was randomized.

Experimental Protocol

 

Series 1
All animals were fasted for 24 hours prior to

the experiment. On the day of the experiment, the animals
were exercised and allowed to defecate and urinate approxi-
mately 30 minutes prior to the start of the experiment.
They were then brought to the experimental area and made
to lie down, whereupon the cannulas were flushed and
filled with normal saline. The arterial pressure catheter
was attached to a Statham Pressure Transducer (Model No.
P 23 Gb) and systemic arterial pressure was recored on a
Sanborn Model 964 recorder. After a steady arterial pres-
sure recording had been obtained for fifteen minutes, the
first microsphere injection was prepared.

The microspheres were injected into the left atrium
while a reference arterial blood sample was withdrawn
from the mammary artery with an infusion/withdrawal pump
(Harvard, Model 901, Dover, Massachusetts) at a rate of

7.75 ml/min for two minutes. Systemic blood pressure and

15

heart rate were monitored prior to and after microsphere
injection. Upon completion of the injection, both cannulas
were capped and the dog was free to move about. The dog
was not allowed to see or smell food until the first
microsphere injection (control) had been completed. The
dog was then given a meal of a commercial dog food con-
taining 12% protein and 7% fat (Alpo Beef Chunks, Allen
Products Co., Allentown, Pennsylvania) and water and was
allowed to eat undisturbed.

The second and third microsphere injections were made
thirty and ninety minutes after completion of the meal.
The procedure for each injection was the same as the first
and the animal was allowed to move about between injections.
Upon completion of the third injection, the animal was
sacrificed with sodium pentobarbital and an intracardiac

injection of a saturated potassium chloride solution.

Series 2
In this series, the surgical preparation and
experimental procedure were identical to Series 1 except
that the animals were not fed during the experiment. The
second and third injections were made at times corresponding

to the 30 and 90 minute injections in the test series.

Tissue Sampling

 

After the animal was sacrificed, duplicate samples
of tissue were taken from the organs to be studied in
order to determine their radioactivity. Each sample was

placed in a pre-weighed disposable counting tube and

l6
weighed. Sample weight was determined by subtracting the
weight of the tube from the weight of the tube and sample.
The samples weighed approximately one gram and filled the
tube to a height of 1 to 2 cm. The organs studied and
the method of sampling are as follows:

Reference_Arterial Sample: The blood collected
during the injection period was heparinized and placed in
disposable plastic counting tubes. The withdrawal rate
was divided by the total radioactivity of the sample to
provide a constant for the conversion of radioactivity
(counts/min) to blood flow (ml/min).

Skeletal Muscle: Eight to ten random samples of

 

muscle were taken from both the forelimb and hindlimb of
the animal. The average of the blood flows determined
from these samples is reported.

H3333: Four random samples were taken from the left
ventricle and two random samples were taken from the right
ventricle. The average flow for each ventricle is reported.

Adipose Tissue: At least two random samples of fat

 

were taken from the abdominal cavity with an additional
two to four samples taken from other regions of the body
when available. The average of the available samples is
reported.

£1121: Duplicate samples were taken from each lobe
of the liver and the average of all the samples is
reported as hepatic artery blood flow. There is some

error in this method due to hepatic trapping of microspheres

17
passing through the arterio-venous shunts of the intes-
tinal tract; however, it is small (2-3%) (21,29).
Pancreas: Duplicate samples were taken from both
the head and tail region and the average blood flow in
each region is reported separately.

Adrenal Glands: Either the left or right adrenal

 

gland was removed and the whole was counted. The blood
flow reported is calculated from the total radioactivity
of the organ.

B1112: The entire brain was removed and divided into
seven regions based on the standard anatomical landmarks
(Medulla, Pons, Thalamus-Midbrain, Hypothalamus, Pituitary,
Cerebellum and Cerebrum). Each region was then divided
into the standard one gram samples and the radioactivity
of all samples from each region was counted and added to
give the total radioactivity from which the total blood
flow to each region was calculated. Total brain blood
flow was calculated using theweighted average of the
regional blood flows. Additionally, blood flow to the
grey and white matter of the brain was determined from
random samples of the caudate nucleus and corpus callosum,
respectively.

Gastrointestinal Samples: All samples of the stomach

 

and intestinal wall were divided into duplicate samples

of the mucosal, submucosal and muscularis layers by blunt
scraping. An average blood flow was calculated for each

portion of the wall and total wall flow was calculated as

18
the weighted average of the three layers. The weight dis-
tribution of the three layers is taken from the work of
Yu (67). The following samples were taken:
a) Stomach Body
b) Stomach Antrum
c) Duodenum, within 15 cm of the pylorus
d) Proximal Jejunum, within 5 cm of the ligament
of Treitz
e) Distal Jejunum, taken approximately 100-150 cm
from the ligament of Treitz
f) Ileum, within 15 cm of the ileocecal juncture
g) Proximal Colon, within 35 cm of the ileocecal
juncture

h) Distal Colon, within 35 cm of the rectum

Calculation of Blopd Flow

 

The radioactivity of all samples was measured using

the Searle 1185 series gamma counter. The energy windows

46Sc, 700-1150 keV; 85 141

used were Sr, 464-564 keV; Ce,
95-195 keV. Separation of the isotope peaks was accom-
plished using a preprogrammed Wang 800 series computer.
Radioactivity was expressed as counts per minute and blood
flow was calculated from the following formula:
CS x 100 x RBF
BF = C
r

 

where BF = blood flow to the tissue or organ in ml/min/

100 gm; C3 = counts/gm of sample; RBF = reference blood

19
flow (rate of withdrawal from the reference artery); and

Cr = total counts in the reference blood sample.

Expression of Data and Statistical Methods

The calculated blood flow for each organ at control,
30 and 90 minutes in both series is expressed as the mean
1 the standard error of the mean (Mean 1 S.E.M.). The
blood flow in a tissue or an organ at thirty minutes was
compared to control and blood flow at ninety minutes was
compared to control levels using Student's t-test for
paired comparisons (49). The level of significance was

taken at P<0.05.

CHAPTER IV
RESULTS

The animals in this study exhibited no outward signs
of distress during the injection of microspheres. Between
injections, the animals either remained in a resting posi-
tion or moved to another area of the laboratory and lay
down. During both series of experiments, arterial blood
pressure and heart rate remained constant. The average
control arterial blood pressure in the test series was
96 1 3.1 mm Hg and the heart rate was 133 1 8.7 beats/min.
In the fasted series, the average control arterial blood
pressure was 96 i 8 mm Hg and the heart rate was 130 i 15
beats/min.

As seen in Table 1, blood flows to the various regions
of the brain in the test series were not significantly
altered 30 and 90 minutes after feeding with one exception.
Blood flow to the cerebral hemispheres significantly
decreased by 8.28 ml/min/100 gm (-14 percent) 30 minutes
after completion of the meal. This resulted in a correspond-
ing significant decrease in total brain blood flow of
7.27 1 2.18 m1/min/100 gm (-12 percent). However, as indi-
cated in Table 2, the pattern of total and regional brain

blood flow in the test series is identical to that of the

20

21

Table 1. Mean 1 S.E.M. total and regional blood flow
(ml/min/lOO gm) to the brain in the conscious
dog before and after feeding

 

 

Region Time (min) after feeding
-10(Control) 30 90

Medulla 37.931 2.78 35.091 2.92 37.28: 3.47
Pons 49.38: 4.69 44.801 5.88 48.631 6.14
Thalamus-Midbrain 59.32: 3.72 54.91: 4.78 53.18: 5.10
Hypothalamus 61.40: 7.41 55.05: 9.27 55.15: 5.85
Pituitary 104.50:15.38 125.40:22.35 129.04:34.01
Cerebellum 64.22: 2.97 55.84: 5.05 60.88: 5.87
Cerebral 61.06: 3.34 52.80: 4.43* 54.15: 4.09
Hemispheres

Grey Matter 98.90: 8.72 96.09: 7.34 91.39: 8.33
White Matter 21.91: 1.66 18.99: 3.41 18.93: 2.31
Total 59.60: 3.26 52.33: 4.39* 53.51: 4.16

 

9:
Values are statistically significant relative to
control at P<0.05, N = 8.

22

Table 2. Mean 1 S.E.M. total and regional blood flow
(ml/min/100 gm) to the brain in the conscious

 

 

fasted dog
Region Time (min) of measurement*
-10(Control) 30 90
Medulla 39.981 3.51 38.531 3.61 43.211 9.72
Pons 54.961 9.57 51.79: 8.43 56.95113.44

Thalamus-Midbrain 62.12: 5.91 57.26: 9.01 60.83:10.26

 

Hypothalamus 69.79:ll.l9 68.87111.72 79.09:25.l3
Pituitary 122.75164.58 153.34:43.41 170.69175.81
Cerebellum 62.59: 3.83 59.08: 7.78 68.68:10.l4
Cerebral 59.09: 8.16 51.67: 8.16** 56.60:13.42
Hemispheres

Grey Matter 97.57:10.20 91.14:l6.22 97.85:24.49
White Matter 19.801 1.23 20.741 1.65 26.98: 3.81
Total 58.83: 7.39 52.441 7.61** 57.76:12.62

1

Measurements were taken at times corresponding to
those in the test series.
**
Values are statistically significant relative to
control at P<0.05, N = 4.

23
fasted series. At the time corresponding to the first
postprandial measurement of blood flow in the test series,
the average blood flow to cerebral hemispheres and total
brain in the fasted series decreased by 8.32 : 0.90
(~12 percent) and 7.75 1 1.60 m1/min/100 gm (-11 percent),
respectively. These changes are not statistically dif-
ferent from those in the test series (P>0.05, Student's
t-test, unpaired comparison).

Tables 3 and 4 show the average blood flows to various
organs and tissues. Blood flow to the skeletal muscle,
right and left ventricles of the heart, the adipose tissue
and the adrenal gland showed no significant change 30 or
90 minutes after feeding (Table 3). Hepatic artery blood
flow, however, decreased significantly from 61.03 : 13.30
to 37.57 i 8.24 m1/min/100 gm thirty minutes after feeding
and remained below control levels at 42.00 : 6.75 ml/min/lOO
gm ninety minutes after feeding. Blood flow to the pan-
creatic head and tail increased markedly at thirty and
ninety minutes after feeding. The blood flow in the head
region of the pancreas nearly doubled at thirty minutes
from the control level of 170.58 : 30.01 ml/min/100 gm
to 301.78 i 37.88 ml/min/100 gm and reached 343.63 :

93.95 ml/min/100 gm within ninety minutes of feeding. In
the tail region, blood flow rose markedly from a control
level of 149.37 : 28.39 ml/min/lOO gm to 300.92 : 32.75
ml/min/100 gm within thirty minutes and peaked at 324.35 :

98.31 ml/min/100 gm ninety minutes after feeding. In the

Table 3. Mean

24

S.E.M. blood flow (ml/min/100 gm) to

various organs of the conscious dog before and
after feeding

-—--——-———.—-——.— _____.__—_.__._—._— _—__-—-_—__—
_._..___-_-.———.—‘._=__——_.‘. ____—____.__-:=—=___-_.-_-—=— ———-—~——--—————-—-—-———-

Time (min) after feeding

 

 

-10(Control) 30 90
Skeletal Muscle 5.171 0.91 3.841 0.80 3.881 1.14
Right Cardiac 54.841 7.80 51.521 6.67 51.171 8.55
Ventricle
Left Cardiac 95.74115.73 78.71110.23 81.66114.52
Ventricle
Adipose Tissue 12.021 2.57 18.761 4.09 8.451 3.34
Adrenal Gland 288.23:39.45 306.36158.20 285.02147.04
Liver (Hepatic 61.03:13.30 37.57: 8.24* 42.00: 6.75*
Artery)
Pancreas Head l70.58:30.01 301.78:37.88* 343.63:93.95*
Pancreas Tail l49.37:28.39 300.92132.75* 324.35198.31*

 

*
Values are statistically significant relative to
control at P<0.05, N = 8.

25

fasted series (Table 4), blood flow to the skeletal
muscle, right and left ventricles of the heart, the
adrenal gland, the liver and both the pancreatic head and
tail was unchanged. Blood flow to the adipose tissue in
the fasted series, however, did decrease from the control
value of 12.54 1 3.35 ml/min/lOO gm to 6.79 : 3.36
ml/min/100 gm at the time corresponding to ninety minutes
after completion of the meal in the test series.

The average total and regional blood flows to the
wall of the gastric body in both the fasted and test
series can be seen in Table 5, while that of the gastric
antrum can be seen in Table 6. In both cases, there were
no significant changes in blood flow to the three layers
of the stomach wall or in total wall flow in either
series. In order to prove that the radioactive micro-
sphere technique is capable of detecting an increase in
gastric blood flow in our eXperimental setting, 1.0 mg
of histamine phosphate was administered subcutaneously
to a conscious dog. As shown in Figure 1, blood flow
to the whole wall and mucosa of the gastric body and
antrum was markedly increased despite a decrease in sys-
temic arterial blood pressure of 15 mm Hg.

The effects of feeding on the total and regional
blood flow of the duodenum are demonstrated in Table 7.
Blood flow to the mucosal layer of the duodenum rose from
a control level of 113.30 1 21.03 ml/min/lOO gm to 219.99
: 68.85 ml/min/lOO gm at thirty minutes after feeding and

then to 228.97 1 40.03 ml/min/100 gm ninety minutes after

26

Table 4. Mean 1 S.E.M. blood flow (ml/min/lOO gm) to
various organs of the fasted conscious dog

================== =========== ==============================

 

 

 

Organ Time (min) of measurement*
-10(Control) 30 90
Skeletal Muscle 2.391 0.73 2.931 0.20 2.881 0.44
Right Cardiac 45.621 2.90 45.641 3.09 51.671 4.34
Ventricle
Left Cardiac 81.921 2.16 75.761 8.62 93.401 5.09
Ventricle
Adipose Tissue 12.54: 3.35 5.88: 1.67 6.79: 3.36**
Adrenal Gland 323.17140.63 382.15:54.63 368.00:48.78
Liver (Hepatic 35.681 0.78 37.621 4.02 30.021 7.22
Artery)
Pancreas Head 197.16:59.3l lZ3.75:28.48 127.85:26.45
Pancreas Tail 190.68:68.20 116.15:22.05 118.62:28.44
*

Measurements were taken at times corresponding to
those in the test series.

**

Values are statistically significant relative to

control at P<0.05, N

4.

27

Table 5. Mean 1 S.E.M. total and compartmental blood flow
(ml/min/100 gm) to the wall of the gastric body
in the conscious dog

—’—-—~——-_‘—_——--—-_—-——_——_-___-—n—_ ~_—_-—n——.—_-——.——-—_——_--———_-a——_
—_____—__--_——_-—_-.—_~__-____—_.—=—_-—_—.—.-__—_———.—-——_——-——_-—_

Time (min) after feeding

 

 

 

Compartment -10(Control) 30 90

Fed N = 8

Mucosa 81.24118.67 64.29113.55 75.11120.00
Submucosa 8.42: 3.81 3.46: 1.54 6.88: 3.51
Muscularis 5.271 0.98 4.06: 0.74 6.09: 1.40
Total Wall 43.821 9.32 33.991 6.81 40.67110.42

Fasted N = 4

 

Mucosa 109.47112.67 88.25:16.94 83.92:15.60
Submucosa 3.20: 1.34 6.67: 3.17 3.64: 1.30
Muscularis 11.04: 6.16 13.60: 5.05 30.80:18.15

Total Wall 59.73: 8.11 49.45: 8.91 53.32:11.12

 

28

Table 6. Mean 1 S.E.M. total and compartmental blood flow
(ml/min/100 gm) to the wall of the gastric antrum
in the conscious dog

——.—————————~—_—-——.—_— -___——_-_——————-———-.¢——————o-—-.—_——o_——.—_———————.-.
__———————_—-_—o———_———-_-—-—.————_—n———-—-_’—-_————.-——¢--—-__———-“_«

Time (min) after feeding

 

 

 

Compartment ~10(Control) 30 90

Fed N = 8

Mucosa 93.06118.22 137.01:34.06 l43.44:41.lO
Submucosa 17.10: 9.60 15.85: 8.61 13.96: 5.31
Muscularis 11.15: 2.55 7.80: 1.71 9.79: 1.17
Total Wall 53.23:10.44 73.84117.42 77.32:20.86

Fasted N = 4

 

Mucosa 59.39115.61 75.25:27.47 47.28: 1.96
Submucosa 7.76: 3.59 15.87: 7.82 13.28: 4.30
Muscularis 9.89: 3.50 16.88: 4.97 16.89: 5.84

Total Wall 34.16: 7.47 45.80:16.37 31.32: 0.09

 

29

Figure l. The effects of histamine on the total and
regional blood flow (ml/min/100 gm) to the wall of the
gastric body and antrum.

At -10 minutes, a control measurement of blood flow was
made. At 0 minutes, the dog ate only a small portion of
the meal. At 90 minutes, a second measurement of blood
flow was made and immediately thereafter 1.0 mg of hista-
mine phosphate was injected subcutaneously. At 120
minutes, a third flow measurement was made. N = l

Mucosa ._ O
Submucosa X _ X
Muscularis ‘—‘

Total Wall E] — [j

 

BLOOD FLOW

BLOOD FLOW

ml/min/IOO gm

meMAOOgm

3O

STOMACH BODY

 

 

 

 

 

 

 

 

 

 

500 HISTAMINE o .
400
3 n
(n-oze)
200 r“.
.W" C]
100 D—— (R-O.70)
/
20w
lo. p__‘!—_————-A
‘__1
on x? x x
'10 0 30 60 90 120
TIME-MIN
300 STOMACH ANTRUM
Husrmmao .
250
200
150 :
. 1.. . (Ia-0.49)
100 .— /
so {'1 SIR-LZS) x
o l/‘
40 0 30 60 90 120
TIME'MIN

Figure 1

31

Table 7. Mean 1 S.E.M. total and compartmental blood flow

(ml/min/100 gm) to the wall of the duodenum in

the conscious dog

————-———._—_——_——.¢——-_——-——_-—_—-—‘——-‘-———_.._—--“~ -—_——-_—————-
———-—--—_____.___-____._._....__.._—.-__._._.__.__..._...._._._._._-————-—-—-=-—-————--————-——

Time (min) after feeding

 

 

 

 

Compartment -10(Control) 30 90

Fed N = 8

Mucosa 113.30121.30 219.99168.85* 228.97140.03*
Submucoa 4.661 1.43 18.84117.28 15.97:l3.89

Muscularis 10.991 2.23 14.00: 2.21 13.55: 3.19

Total Wall 78.44114.33 151.72145.70* 157.28126.46*
Fasted N = 4

Mucosa 129.33110.12 171.62114.12* 118.48153.48

Submucosa 11.371 6.38 7.571 2.42 2.98: 1.36

Muscularis 14.291 3.60 14.371 3.48 13.501 4.32

Total Wall 90.701 8.67 117.721 9.43 104.61112.72

 

*
Values are statistically significant relative to

control at P<0.05.

32
feeding. Blood flow to the submucosa and muscularis
remained constant throughout the experiment. As a result,
blood flow to the total duodenal wall increased from
78.44 1 14.43 ml/min/100 gm to 151.72 1 45.70 ml/min/lOO
gm within thirty minutes of feeding. Ninety minutes
after feeding, it reached 157.28 1 26.46 ml/min/100 gm.
In the fasted series, blood flow to the mucosal layer of
the duodenum was also significantly above control levels
at the time of the second microsphere injection. However,
total blood flow to the wall of the duodenum was not sig-
nificantly altered in the fasted series (Table 7).

The average total and regional blood flows to the
proximal jejunum are shown in Table 8. As can be seen,
there were no changes in total or regional blood flow in
this portion of the jejunum in the fasted series. In the
test series, however, the pattern of response was identical
to that of the duodenum. Mucosal blood flow more than
doubled from 114.25 : 25.70 ml/min/lOO gm to 270.72 1
84.01 ml/min/lOO gm within thirty minutes of feeding and
then rose to 295.06 : 70.11 ml/min/100 gm ninety minutes
after completion of the meal. Again, submucosal and
muscularis blood flow remained unchanged resulting in an
increase in blood flow to the jejunal wall from 74.76 1
16.36 ml/min/100 gm to 180.63 : 51.33 m1/min/100 gm and
then to 193.07 : 42.97 ml/min/100 gm. As seen in Table 9,
however, neither total nor compartmental blood flow changed
in the wall of the distal jejunum in either the test or

fasted series.

33

Table 8. Mean 1 S.E.M. total and compartmental blood flow
(ml/min/100 gm) to the wall of the proximal
jejunum in the conscious dog

_——__—_—-—.--——._ ‘—_—-__-—-_—_—g—-——_-—-—.—.—.—.-_———————-—‘__-_———._—._—
-——.—_—.—-—- -———————_——_——_—C-—_.—_——_ -.—_‘—.———.-—‘——-———..-_-_-.——_—_--———

Time (min) after feeding

 

 

 

Compartment -10(Control) 30 90

Fed N = 8

Mucosa ll4.25125.70 270.72184.01* 295.06:70.ll*
Submucosa 9.911 4.84 22.37118.26 38.99135.77

Muscularis 5.951 1.84 28.23:13.13 9.011 1.54

Total Wall 74.76116.36 180.63151.33* l93.07:42.97*

Fasted N = 4

 

Mucosa 143.34:23.l4 173.09132.69 l93.93:36.57
Submucosa 12.63: 5.80 15.97: 8.44 9.53: 3.86
Muscularis 12.48: 5.63 11.02: 2.44 11.501 3.41
Total Wall 95.48:lS.46 114.17119.55 l34.941l6.23

 

*
Values are statistically significant relative to
control at P<0.05.

34

Table 9. Mean 1 S.E.M. total and compartmental blood flow
(m1/min/100 gm) to the wall of the distal
jejunum in the conscious dog

-——.——_———u__-—_. -—_—-_'_———_—_—._-_—.—c——...-_—__.-———-—4——_._—————-——-—-————-———~—-—
__--_-—_-_-—_-——— .——_—__—.--— —-——_———-——--—_-_——_—‘—.—_——-—————--————————

Time (min) after feeding

 

 

 

Compartment -10(Control) 30 90

Fed N = 8

Mucosa 156.32134.82 207.89159.38 255.45159.45
Submucosa 10.191 4.82 10.821 6.28 6.181 2.43
Muscularis 11.67: 1.63 12.721 3.07 7.53: 2.36
Total Wall 89.68125.14 l36.13137.27 164.14137.81

Fasted N = 4

 

Mucosa 126.29117.21 157.84140.19 116.92:18.93
Submucosa 3.641 0.58 6.45: 2.28 2.53: 1.79
Muscularis 6.211 1.49 12.811 4.12 5.91: 1.21

Total Wall 81.68:ll.09 103.57:26.09 75.57:12.08

 

35

In the ileum, there were no changes in either total
or compartmental blood flow in the fasted animal, nor
were there any changes thirty minutes after feeding in
the test series (Table 10). Ninety minutes after comple-
tion of the meal, however, mucosal flow in the ileum of
the fed dog increased from a control level of 127.71 :
30.40 ml/min/100 gm to 238.77 1 70.42 ml/min/100 gm. As
before, there were no changes in submucosal or muscularis
blood flow and consequently total blood flow to the ileal
wall rose from 74.06 : 17.08 ml/min/lOO gm prior to feed-
ing to 136.17 : 38.50 ml/min/lOO gm ninety minutes after
completion of the meal.

In Table 11, it is evident that total and compart-
mental blood flows were not altered in the proximal colon
in either series of experiments at thirty or ninety
minutes. This is also true for the distal colon in the
fasted series. As can be seen in Table 12, however,
mucosal blood flow in the distal colon of the test series
did show a marked decrease from 149.65 : 21.70 ml/min/100
gm to 97.77 ml/min/100 gm thirty minutes after feeding.
Neither submucosal nor muscularis blood flow was altered
and total blood flow to the wall of the distal colon fell
from 64.13 i 7.96 m1/min/100 gm to 39.44 : 7.19 ml/min/100
gm. A11 blood flows returned to control levels ninety

minutes after completion of the meal.

36

Table 10. Mean 1 S.E.M. total and compartmental blood flow
(ml/min/100 gm) to the wall of the ileum in the
conscious dog

——-__-_.___————.._.—_____-_-—_-_—___.-__- _. _...___ __———_———_-_co_——_—————_.
_‘——-—--_4-——_--——.—--—_—_—-—-—c—-=_=——-—--=.-_—-—_————-—---‘—r—————

Time (min) after feeding

 

 

Compartment -10(Control) 30 90

Fed N = 8

Mucosa 127.71:30.40 93.12:17.73 238.77:70.42*
Submucosa 2.60: 0.64 4.201 2.28 7.34: 5.22

Muscularis 9.12: 1.49 13.38: 4.81 9.19: 1.84

Total Wall 74.06:17.08 56.34: 9.63 136.17138.50*

Fasted N = 4

 

Mucosa 150.73153.58 150.70155.l4 l35.47:52.65
Submucosa 7.77: 3.41 7.44: 2.26 3.31: 1.25
Muscularis 14.12: 7.05 8.03: 2.02 6.86: 1.26
Total Wall 89.17128.87 86.64129.77 77.55129.73

 

*
Values are statistically significant relative to
control at P<0.05.

37

Table 11. Mean 1 S.E.M. total and compartmental blood flow
(m1/min/100 gm) to the wall of the proximal colon
in the conscious dog

_____.-__.- __—_— —________—__—.___—___ ___.__—_.__.___.-____ __.—_.._—____.__
__--_—_—.__.__._.__.__—___—_-____-—.——_.————__———__‘3:.—_-._—__....__

Time (min) after feeding

 

 

 

Compartment -10(Control) 30 90

Fed N = 8

Mucosa 153.47133.73 l39.65140.15 lS7.90:42.65
Submucosa 19.05110.62 5.61: 2.72 10.95: 4.37
Muscularis 8.371 2.42 8.001 3.74 10.69: 7.21
Total Wall 62.74111.55 53.15114.11 63.88115.94

Fasted N = 4

 

Mucosa 257.95:12.83 316.49:35.01 250.00:3S.40
Submucosa 8.11: 2.37 11.64: 4.86 7.44: 3.68
Muscularis 6.13: 1.26 9.83: 3.77 5.26: 1.38

Total Wall 97.40: 3.69 120.87114.22 94.02:12.82

 

38

Table 12. Mean 1 S.E.M. total and.compartmental blood flow
(ml/min/lOO gm) to the wall of the distal
colon in the conscious dog

—. —-———-————o_—~——— -_—.-_——_-—._-_-——— -.—_-— -—-_———-——%———————-———_——_—-_._
d-—<——-_—_—_—-—-_ ._.—.-t—-.—-——-.-—_——-—c..-——-=-——.——.——_¢———.---—.-o—————————--

Time (min) after feeding

 

 

 

Compartment -10(Control) 30 90

Fed N = 8

Mucosa 149.65121.70 97.77120.95* 139.02:40.24
Submucosa 25.51:11.71 12.31: 9.10 14.72: 9.28
Muscularis 11.84: 4.32 4.11: 1.31 10.93: 5.52
Total Wall 64.131 7.96 39.441 7.19* 58.05:16.95

Fasted N = 4

 

Mucosa 174.69144.59 230.17:70.72 l72.98:43.02
Submucosa 11.15: 5.33 13.14: 5.05 7.84: 2.43
Muscularis 6.26: 1.02 10.57: 6.10 4.94: 1.62
Total Wall 67.97:15.53 90.32:25.78 66.14:15.ll

 

*
Values are statistically significant relative to
control at P<0.05.

CHAPTER V

DISCUSSION

It has been well established that splanchnic blood
flow increases after a meal in man (14,46,50), primates
(65) and dogs (6,12,13,27,37,63,64). Furthermore, the
most recent evidence indicates that cardiac output (6,12,
13,27,37,50,63-65), renal blood flow (64,65) and coronary
blood flow (64,65) are transiently altered during inges-
tion but return to control levels fifteen to thirty
minutes after completion of the meal. There is some evi-
dence indicating a postprandial decrease in blood flow to
the extremities in the conscious dog (27,64,65) and one
study reports that hepatic artery blood flow remains at
control levels during digestion while portal venous blood
flow and consequently total hepatic blood flow increases
(37). Although the postprandial distribution of blood
flow among the layers of the wall of the gastrointestinal
tract has been studied, the results are contradictory.
Studies in anesthetized dogs have shown that blood flow
increases only in those portions of the small intestine
actually exposed to chyme (16,61) and that this is due
solely to an increase in blood flow to the mucosal layer
of the intestinal wall while flow to the submucosa and
muscularis remains constant (16,67). A recent study in

39

40
conscious dogs, however, suggests that blood flow
increases in all compartments of the intestinal wall
during digestion (6). Although a feeling of drowsiness
is often experienced after a heavy meal, the possibility
that this may be associated with a change in either
regional or total brain blood flow has not been examined.
In addition, the effects of digestion on blood flow to
the pancreas, adrenal glands and adipose tissue in the
conscious dog are unknown. The purpose of this study,
therefore, was to use the radioactive microsphere tech-
nique to examine the effects of digestion on blood flow
to the brain, pancreas, adrenal glands and adipose tissue
and to further examine the postprandial distribution of
blood flow within the brain and the wall of the gastro-
intestinal tract in the conscious dog.

The validity of the microsphere method for determining
both total and regional organ blood flow has been well
established (2,3,15,21,22,29,36,39,47,66,67). The blood
flows reported in this study fall within the range of
flows reported in the literature for the brain (50-70 ml/
min/100 gm) (26,47), adipose tissue (7-12 ml/min/100 gm)
(4), muscle (2-5 m1/min/100 gm) (26), heart (60-80 m1/min/
100 gm) (26), adrenal glands (300-400 ml/min/100 gm) (60),
stomach (40-60 ml/min/100 gm) (22), small intestine (70-90
ml/min/lOO gm) (15,29) and large intestine (60-80 ml/min/
100 gm) (15). Blood flow to the pancreas was considerably
higher than reported in previous papers, but this may be

due to a depression of pancreatic blood flow as a result

41

of the extensive surgical preparation and anesthesia
required in earlier studies. Hepatic artery blood flow
at the control injection in the fed series was higher
than has been reported in other studies (37,41). The
submucosal and muscularis blood flows reported here are
less than those reported by other authors (2,22,29) but
are consistent With other studies within this laboratory.

As seen in Table 1, total brain blood flow decreases
slightly thirty minutes and then returns to control ninety
minutes after a meal. This decrease in total brain blood
flow thirty minutes after feeding is due to a correspond-
ing decrease in flow to the cerebral hemispheres while
blood flow to the other regions of the brain remains
unchanged. However, as shown in Table 2, both total and
regional brain blood flow in the fasted series follow
the same pattern and, in the case of total and cerebral
hemisphere blood flow, the degree of change is the same
(P>0.05, Student's t-test, unpaired comparison). The
treatment of the animals and the method of injection were
identical in all experiments and no behavioral differences
were noted between the animals of either series. Since
the results are identical in both the experimental and
control series, the decrease in brain blood flow must have
been caused by some common factor which is unrelated to
the digestive state of the animal. Therefore, it must be
concluded that digestion has no effect on either regional

or total brain blood flow.

42

Skeletal muscle blood flow was not significantly
changed in either the test or control series, as shown
in Tables 3 and 4. This study agrees with that of Fronek
and Stahlgren (27), who found that digestion had no
effect on blood flow through either the brachiocephalic
or iliac arteries during the first 90 minutes of digestion.
Although Vatner et al. (64,65) reported a slight increase
in iliac artery resistance during the first hour after
feeding, they stated that this was abolished or reversed
if the animal arose or changed position during this period
and in no case did it last beyond one hour.

As seen in Tables 3 and 4, blood flow to the right
and left cardiac ventricles remained constant in both
series of experiments. This finding supports the results
of a study by Vatner et al. (64) of the effects of diges-
tion on coronary blood flow in conscious dogs. In their
study, Vatner et a1. measured the blood flow through the
left circumflex coronary artery with electromagnetic
flowmeters and reported that, with the exception of a
transient increase during ingestion, coronary artery
blood flow remained at control levels throughout the
postprandial period.

Blood flow to the adrenal glands remained constant
in both series of experiments, as seen in Tables 3 and 4,
as did blood flow to the adipose tissue in the test series
(Table 3). Blood flow to the adipose tissue in the control
series was significantly decreased at the time correspond-

ing to ninety minutes after feeding in the test series

43

(Table 4). This result, however, is difficult to interpret
given the sensitivity of this vascular bed to even low
levels of sympathetic neural activity or circulating
catecholamines. It has been shown that stimulation of
the sympathetic nerves to canine adipose tissue causes
vasoconstriction (51) and, although the response is more
variable, circulating catecholamines can have the same
effect (4). Therefore, it is possible that sympathetic
activity increased during the experiment in the control
series due to the stress of a prolonged fast and resulted
in a decrease in blood flow to the adipose tissue at the
time of the last injection. It is also possible that
this change in blood flow may be due to technical error.

Table 5 shows that blood flow to the gastric body
was not significantly different from control at thirty
and ninety minutes after completion of the meal. It was
expected that flow to the gastric body and/or antrum
should increase following a meal or at least thirty
minutes after a meal as gastric juice and gastrin secre-
tion are increased during this period. Thus, in order to
verify the ability of the microsphere technique to detect
changes in gastric blood flow in this experimental setting,
histamine phosphate (1 mg) was administered subcutaneously
in one dog and blood flow was measured thirty minutes
later. Histamine administered at this dose (40 ug/kg)
subcutaneously has been shown to stimulate hydrogen ion
secretion within thirty minutes (48) and produce an increase

in blood flow to the wall of the stomach (2). As seen in

44
Figure 1, blood flow to the wall of the gastric body and
antrum doubled within thirty minutes of the administra-
tion of histamine. Therefore, the pattern of gastric
blood flow during digestion as seen in this experiment,
Tables 5 and 6, is a real phenomenon and is not due to
technical error.

In the small intestine, blood flow increased sig-
nificantly in the duodenum and proximal jejunum thirty
minutes after feeding while flow to the distal jejunum
and terminal ileum remained at control levels (Tables 7,
8, 9 and 10). Ninety minutes after feeding, blood flow
to the duodenum and proximal jejunum remained elevated
while flow to the distal jejunum was unchanged and flow
to the terminal ileum increased significantly. Thus, in
the small intestine the postprandial hyperemia appears to
be confined to the proximal regions during the early
stages of digestion and subsequently spreads to the more
distal regions. An angiographic study in man has also
shown that blood flow to the duodenum and upper jejunum
increases within twenty minutes after a meal of ice cream
(46). Furthermore, Chou et a1. (16) have found that in
anesthetized dogs blood flow in the small intestine
increases only in those areas exposed to digested food.
Thus, the pattern of blood flow changes in the small
intestine observed in this study appears to follow the
aboral flow of chyme in the small intestine.

A fluoroscopic study has shown that a portion of a

meal containing barium can reach the upper jejunum as early as

45
five minutes after a meal (50), while examination of the
gastrointestinal tract at autOpsy in this study clearly
demonstrated that chyme was present in all regions of
the small intestine at the time of the last measurement.
Thus, at 30 and 90 minutes after a meal, chyme containing
the digested products of food is present in the duodenum
and proximal jejunum resulting in an increase in blood
flow to those regions. Although chyme may not have
reached the distal jejunum 30 minutes after feeding, it
is known to have been present ninety minutes after the
meal and yet the blood flow to this region was not sig-
nificantly different from control at either time. This
may be due to the fact that even if the chyme were present
in this region, it may not have contained a sufficient
amount of the digested products of food to produce a
hyperemia. Borgstrom et a1. (7) have shown that in
humans 90 to 100 percent of all fat, carbohydrate and
protein present in chyme is absorbed within the first
100 cm of the jejunum. Studies in this laboratory have
shown that the constituents of chyme responsible for the
postprandial hyperemia in the jejunum are the digested
products of food (45,58) and that the hyperemic effect
depends on the concentration of the nutrients (43). Thus
a solution containing 20% or more of digested food made
from the same dog food as used in this study can produce
a significant increase in jejunal flow but a 10% solution
of that same digested food cannot (43). Neither undigested

food nor bile in the jejunal lumen can produce an increase

46
in jejunal blood flow. Therefore, the absence of a
hyperemia in the distal jejunum during this experiment
is probably due to the fact that chyme containing the
amount of nutrients necessary to produce a hyperemia does
not reach this region within the first ninety minutes
after feeding. Although bile in the jejunum does not
alter jejunal blood flow, bile in the ileal lumen does
produce a marked increase in blood flow to the ileum (44).
Thus, blood flow to the ileum is not altered thirty
minutes after feeding (Table 10), probably because chyme
has not yet reached this region but at ninety minutes it
has reached the ileum and the bile in the chyme produces
a significant increase in ileal blood flow (Table 10).

In all cases where blood flow to the wall of the
small intestine increased during digestion, it was due
solely to an increase in blood flow to the mucosal layer
of the intestinal wall while blood flow to the submucosa
and muscularis remained at control levels. This finding.
is in agreement with that of Chou et al. (16,67) in the
anesthetized dog but contradicts that of Bond and Levitt
(6) in the conscious dog. The study by Bond and Levitt,
however, is subject to some criticism. Several investi-
gators (2,29,31) have suggested that while the microsphere
method can clearly distinguish muscularis flow from that
of the mucosa-submucosa, it may not be able to separate
the mucosal and submucosal flows when the size of the
spheres is not uniform. Microspheres are found to be

preferentially trapped in the submucosa as Sphere diameter

47

increases, although the sum of mucosal and submucosal
radioactivity remains the same regardless of sphere size,
i.e., they behave as if they were in a single compartment.
Thus when Bond and Levitt divided their samples into villi,
crypts and submucosa-muscularis, they may have been
attributing increases in mucosal blood flow which were
distributed to the submucosa to increases in muscularis
flow. This error could be especially significant if the
microspheres used were of relatively large diameter (the
size of the spheres was not reported in the abstract).

In contrast to the small intestine, blood flow to
the large intestine for the most part remains unchanged
during digestion. As seen in Table 11, blood flow to the
wall of the proximal colon remains at control levels
throughout the experiment. In Table 12, it is evident
that blood flow to the wall of the distal colon is sig-
nificantly decreased thirty minutes but returns to control
levels ninety minutes after feeding. Shortly after a
meal, the feces in the middle colon is rapidly moved
towards the rectum (20) as a result of the gastro-colic
and duodeno-colic reflexes which produce mass movement
in the colon. Chou et a1. (15) have demonstrated that
tonic contraction in the colon results in a decrease in
total wall blood flow due to a decrease in flow to the
mucosal layer. The decrease in blood flow to the wall of
the distal colon thirty minutes after the meal is also

due to a decrease in blood flow to the mucosal layer and

48
may possibly be the result of this phenomenon of mass
movement.

Thus it can be seen that in the intestine, the
presence of chyme in the duodenum and upper jejunum
thirty minutes after feeding produces a significant
increase in blood flow in those regions while flow to
the distal jejunum and terminal ileum remains at control
levels. Simultaneously, there may be a mass movement of
feces from the middle colon to the rectum resulting in
an overall decrease in blood flow to the distal portion
of the colon. Within ninety minutes of feeding, some
chyme has reached the terminal ileum producing an increase
in blood flow to that region, while the increase in blood
flow to the duodenum and proximal jejunum is sustained.
Blood flow to the distal jejunum is not significantly
different from control at either thirty or ninety minutes
after feeding. Blood flow to the large intestine is not
significantly different from control ninety minutes after
completion of the meal. In all cases where blood flow to
the intestinal wall increased, it was due solely to an
increase in flow to the mucosal layer.

In conjunction with the marked postprandial intes-
tinal hyperemia, blood flow to the pancreatic head and
tail nearly doubled thirty and ninety minutes after feed-
ing (Table 3). Several authors have demonstrated a
direct correlation between pancreatic secretory activity
and blood flow in response to various stimuli including

intestinal hormones (23) and the placement of food in the

49
upper jejunum (42). It is probable, therefore, that the
presence of chyme in the upper region of the small intes-
tine thirty and ninety minutes after feeding stimulates
pancreatic secretion which is accompanied by an increase
in pancreatic blood flow as seen in this experiment.

As seen in Table 3, hepatic artery blood flow falls
significantly below control levels thirty minutes and
remains below control levels ninety minutes after feeding.
This finding contradicts that of Hopkinson and Schenk
(37) in which the authors used an electromagnetic flow-
meter to measure hepatic artery, portal venous and hepatic
venous blood flow following a meal. They reported that
hepatic artery blood flow remained constant while portal
venous and consequently total hepatic blood flow increased
significantly. However, Norryd et a1. (50) have shown
that a mean increase in superior mesenteric artery blood
flow of 121 percent in humans can result in a mean increase
in portal venous pressure of 15 percent._ Furthermore,
Hanson and Johnson (33) have shown that in dogs there
exists a reciprocity of flow between the portal vein and
hepatic artery, such that an increase in portal venous
pressure will cause an increase in hepatic artery resist-
ance. Therefore, it is not unreasonable to expect that
a postprandial increase in portal venous blood flow due
to a sustained intestinal hyperemia may cause a decrease
in hepatic artery blood flow as seen in this study.

In general, the present study shows that blood flow

to the brain, heart, adrenal glands, skeletal muscle and

50
adipose tissue is not altered during digestion while
blood flow to the small intestine and pancreas is markedly
increased. Furthermore, all increases in blood flow in
the small intestine are limited to those regions where
chyme is present and are due solely to an increase in
blood flow to the mucosal layer of the intestinal wall.
Blood flow to the body and antrum of the stomach is not
significantly altered thirty or ninety minutes after feed-
ing. Hepatic artery blood flow decreases during digestion
while blood flow to the large intestine remains at control
levels except for a slight decrease in blood flow to the
distal colon thirty minutes after feeding. Thus the
results of this study indicate that the cardiovascular
re5ponse to digestion is limited to those organs actively

involved in the process.

CHAPTER VI
SUMMARY AND CONCLUSIONS

It has been demonstrated that heart rate, cardiac
output, systemic arterial blood pressure and blood flow
through the left circumflex coronary artery, renal artery
and hepatic artery are not altered during digestion while
blood flow through the superior mesenteric artery rises
rapidly within the first thirty minutes of feeding and
remains elevated for several hours. However, there are
no clear data on the effects of digestion on blood flow
to the pancreas, adrenal glands, adipose tissue and
skeletal muscle as well as total and regional blood flow
to the brain and the wall of the gastrointestinal tract.
Therefore, in this study the radioactive microsphere
technique was used to measure blood flow to the major
organs of the conscious dog prior to and thirty and ninety
minutes after feeding. The results indicate that:

1) Blood flow to the heart, adrenal glands, adipose
tissue, skeletal muscle, gastric body and gastric
antrum was not significantly altered during
digestion.

2) The digestive state of the animal has no effect
on either total or regional blood flow to the

brain
51

52

3) Thirty minutes after feeding, blood flow to the

a)
b)
C)
d)
e)
f)

duodenum increases

proximal jejunum increases
distal jejunum is unchanged
ileum is unchanged

proximal colon is unchanged

distal colon decreases

4) Ninety minutes after feeding, blood flow to the

a)
b)
C)
d)
e)
f)

5) In

duodenum remains elevated
proximal jejunum remains elevated
distal jejunum is unchanged

ileum increases

proximal colon is unchanged

distal colon returns to control levels

all cases where intestinal blood flow was

altered during digestion, it was due solely to

a change in blood flow to the mucosal layer while

flow to the submucosa and muscularis remained

unchanged.

6) Blood flow to the pancreas increased during

digestion.

7) Hepatic artery blood flow decreased during

digestion.

These results indicate that the cardiovascular response

to digestion is limited to those organs actively involved

in the digestive processes, that is, the small and large

intestine, the pancreas and the liver. Furthermore, within

the small intestine, the pattern of changes in blood flow

53
appears to follow the aboral movement of chyme down its
length and supports the concept that blood flow increases
only in those regions where chyme is present and absorp-
tion of nutrients or bile is taking place. In addition,
whenever blood flow in the small intestine increases
during digestion, it is due solely to a change in blood
flow to the mucosal layer of the intestinal wall, the
layer in which all postprandial absorption and secretion
occurs. Blood flow to the large intestine is unchanged
during digestion except for a transient decrease in blood
flow to the distal colon thirty minutes after feeding.
This may be associated with the mass movement of chyme
from the middle colon towards the rectum due to a gastro-
colic or duodeno-colic reflex. Blood flow to the pancreas
increases markedly during digestion and is probably related
to an increase in pancreatic secretory activity. Hepatic
artery blood flow, on the other hand, decreases during
digestion, possibly due to the increase in portal venous
blood flow as a result of the postprandial intestinal
hyperemia. This response may be mediated by an autoregula-
tory mechanism known as the "reciprocity of flow" between

the hepatic artery and portal vein.

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