Control of the Splanchnic Circulation in Man

ROLE OF BETA-ADRENERGIC RECEPTORS

By Henry L. Price, M.D., Lee H. Cooperman, M.D., and John C. Warden, M.B.

ABSTRACT
Some effects of the /3-adrenergic receptor blocker, propranolol, were studied
in 20 normal, fasting, conscious men. The measurements made included
cardiac output, splanchnic blood flow and oxygen consumption, arterial and
hepatic venous blood pressure, and heart rate. The intravenous administra-
tion of propranolol (0.13 mg/kg) was followed by significant reductions in
splanchnic blood flow and oxygen consumption, in cardiac output and in heart
rate. Splanchnic perfusion pressure was unchanged; the splanchnic vascular
resistance was significantly elevated. Previous treatment with glucose did not
alter these findings. Phenoxybenzamine prerreatment lessened the increase
in splanchnic vascular resistance which propranolol ordinarily caused. Ganglion-
ic blockade with hexamethonium prevented all of the changes which pro-
pranolol produced in untreated individuals. These results may best be ex-
plained by assuming that the splanchnic circulation in man is influenced both
by a receptors, which cause vasoconstriction when activated, and by /9 recep-
tors, which when activated cause vasodilatation and increase oxygen con-
sumption.

ADDITIONAL KEY WORDS propranolol hexamethonium

alpha-adrenergic receptor blockade splanchnic oxygen consumption
splanchnic vascular resistance phenoxybenzamine
beta-adrenergic receptor blockade

• One of us has reported (1) that the ad-
ministration of propranolol (a /3-adrenergic
receptor blocking drug of high specificity)
to human subjects anesthetized with cyclo-
propane caused a marked reduction in
splanchnic blood flow. This reduction resulted
from increased vascular resistance and was
usually accompanied by a diminution in local
oxygen consumption. Since cyclopropane is
believed to increase the impulse frequency
in sympathetic nerves supplying the abdom-
inal viscera (2), these observations raised
the question whether some of the activity of
From The Department of Anesthesia, University
of Pennsylvania, School of Medicine, Philadelphia,
Pennsylvania 19104.
This work was supported in part by Public Health
Service Grants GM-09070-05 and 5-T1-GM-215-O9
from the National Institute of General Medical Sci-
ences and by a grant-in-aid from Ayerst Laboratories,
Inc., New York. Dr. Cooperman is a Special Fellow
of the National Institutes of Health (1F3-GM-33-126-
01). Dr. Warden is the recipient of a travel grant from
the Postgraduate Medical Foundation, University of
Sydney, Sydney, Australia.
Accepted for publication July 24, 1967.
these fibers caused vasodilation and stimu-
lation of metabolism. If this were true, the
increase in vascular resistance attending the
administration of propranolol could be ex-
plained as the result of reducing or abolish-
ing tonic /3-receptor stimulant activity which
has, to date, remained undiscovered. In the
experiments to be described, this possibility
was examined and found to be likely.
Methods
The subjects studied were 20 healthy, adult,
male volunteers. At preliminary meetings an in-
formed consent was obtained, a medical history
taken, and a physical examination, electrocardio-
gram, urinalysis and blood count were performed.
On the day of study, each subject reported to the
laboratory in the early morning, having fasted
since the previous evening.
Under local anesthesia, a 100-cm no. 7 Lehman
catheter was inserted into an antecubital vein and
advanced as far as possible into a right hepatic
vein and then withdrawn sufficiently (1-2 cm) to
permit free aspiration of blood. In the opposite
arm a 60-cm radiopaque no. 15 catheter, to be
used for dye injection, was inserted percutaneous-
ly into a vein and positioned within the thorax.

Reiisrcb, Vol. XXI, Slplfrnilr 1967 333

Downloaded from http://circres.ahajournals.org/ by guest on March 8, 2015

334 PRICE, COOPERMAN, WARDEN

TABLE 1
General Hemodynamic Changes Following Treatment
Treatment Heart rate (beat'mimin)
Group Subject Ei Ei c Ei E-
I Propranolol
(0.13 mgAg)
3 57 53
4 61 57
5 52 48
6 64 56
32 73 65
Mean 61 56
Significance P < 0.01
II Glucose Propranolol
(20 to 30 g) (0.13 mgAg)
9 68 70 64
10 70 70 66
12 68 67 61
16 79 83 71
19 67 65 62
Mean 70 71 65
Significance P < 0.05
III Phenoxybenzamine Propranolol
(0.75 mgAg) (0.13 mgAg)
27 62 66 61
28 65 72 57
29 71 77 75
30 57 80 63
31 87 102 83
Mean 68 79 68
Significance P<0.05 P<0.05
IV Hexamethonium Propranolol
(0.85 mgAg) (0.13 mgAg)
11 69 84 83
17 63 102 87
18 69 93 87
20 64 95 83
22 86 105 98
Mean 70 96 88
Significance P < 0.01 P < 0.05
Abbreviations: TPR = . peripheral resistance; E2 and E2 = first and second experimental periods; C = control.
Significance: referred to column at left.

Placement of the two catheters was verified by
image-intensification fluoroscopy. A Coumand
needle was placed in the right femoral artery and
cup electrodes were fastened to the skin to permit
recording of the electrocardiogram. Arterial and
hepatic venous pressures were transduced by
Statham strain gauges and recorded, with the
electrocardiogram, on a Grass polygraph. Mean
pressures were obtained by electrical damping.
The reference level for pressure was 5 cm dorsal
to the angle of Louis.
Cardiac output was measured in duplicate by
the indicator-dilution technique using a Waters
densitometer and 5 or 10 mg of indocyanine
green dye. Splanchnic blood flow was estimated
by infusion of indocyanine green dye as described
by Caesar et al. (3) with corrections introduced
by Nielsen (4). No subject extracted less than
5035 of arterial indocyanine gTeen dye in a single
hepatic passage. Splanchnic oxygen consumption
was estimated by multiplying blood flow and the
arteriovenous oxygen content difference as meas-
CirfMon Riurcb, Vol. XXI, Stpumbtr 1967

Downloaded from http://circres.ahajournals.org/ by guest on March 8, 2015

 CONTROL OF THE SPLANCHNIC CIRCULATION 335

Arterial pressure (nun HHf) Cardiac output (Uter/min) TPR (mm Hg/liter per rain)
c Ki Ei C Ei Ei C Ei Ei

87 94 6.25 4.78 13.3 20.5

80 77 5.19 5.10 15.9 15.7
70 75 6.01 5.30 12.0 14.1
91 95 5.07 4.45 18.8 21.3
75 76 4.63 5.87 15.1 13.6

80.6 83.9 5.43 5.10 15.0 17.1

85 87 87 5.68 4.93 15.0 17.3

90 95 90 6.98 5.68 13.6 15.9
87 89 92 8.04 6.25 11.8 14.5
80 83 83 7.73 5.37 10.3 15.5
75 75 75 7.08 4.88 10.6 15.7
83.4 85.8 85.9 7.10 5.42 12.3 15.8
P < 0.01 P < 0.01

76 74 72 6.74 5.60 11.1 13.4

80 68 76 7.56 9.18 6.58 10.3 7.1 6.5
75 75 68 6.30 8.97 6.60 11.9 8.4 10.3
82 74 70 4.66 7.51 4.88 16.1 7.3 13.3
87 75 74 7.05 7.23 7.06 12.8 10.4 10.4
80.0 73.2 72.0 6.39 7.93 6.14 12.8 8.9 10.8
F < 0.05 P < 0.05

85 83 82 5.34 5.62 15.9 15.1

86 77 75 7.52 7.00 11.0 10.3
73 58 71 7.19 9.40 10.4 7.8
85 69 65 7.11 5.84 12.7 11.1
74 67 69 6.75 7.50 10.4 9.7
80.6 70.6 72.4 6.78 7.07 12.1 10.8
P<0.05 P < 0.05

ured by the method of Van Slyke and Neill ( 5 ) .
Similar calculations were used for carbon dioxide
production. Splanchnic vascular resistance was cal-
culated as perfusion pressure (mean arterial minus
mean hepatic venous) divided by the mean rate
of blood flow. Heart rate was counted from the
electrocardiogram. The hematocrit of arterial
blood was determined in capped Wintrobe
tubes spun for 30 min at 2300 X g (at the tip).
Before analysis all blood samples were stored at
4°C.
The tensions of oxygen and carbon dioxide and
Restarcb, Vol. XXI, Stptmbtr 1967
the pH of arterial and venous blood were meas-
ured using an Instrumentation Laboratories elec-
trode assembly model 113-S1. Blood glucose was
determined by an enzymatic method (6).
During the 30-min study period, three deter-
minations of splanchnic blood flow and single
determinations of arterial and hepatic venous
Pco2, Po2) pH, O2 content and CO2 content were
made. Glucose concentration was estimated in 15
individuals. Concentrations of epinephrine and
norepinephrine in arterial plasma were determined
in 11 cases by the method of Price and Price (7).

Downloaded from http://circres.ahajournals.org/ by guest on March 8, 2015

336 PRICE, COOPERMAN, WARDEN

TABLE 2
Local Hemodynamics and Metabolic Changes Following Treatment
Perfuflion preuure (mm Hg) SBF (llter/min) SVR (mm He/liter per min)
Group Subject C Ei Ej c Ei Ei C Ei

i
3 86 91 1.55 .99 57 92
4 78 75 1.50 1.18 52 63
5 69 74 2.66 1.86 26 40
6 87 95 1.60 1.07 55 89
32 74 76 .92 .73 81 104
Mean 78.8 82.2 1.65 1.17 54.3 77.6
Significance P<0.05 P < 0.01
II
9 84 84 84 2.32 2.45 2.36 37 35
10 87 91 87 1.55 1.46 1.31 56 63
12 86 88 91 2.45 2.53 1.94 35 35
16 80 83 82 2.11 2.22 1.61 38 38
19 75 75 75 1.37 1.36 1.12 55 55
Mean 82.4 84.2 83.8 1.96 2.00 1.67 44.1 45.1
Significance P < 0.05
m 53
27 73 73 70 1.68 1.40 1.24 43
28 77 65 75 2.32 1.80 1.27 34 38
29 72 74 66 1.23 1.36 1.07 59 55
30 79 74 70 1.07 1.18 1.04 74 62
31 84 74 74 1.90 1.82 1.42 44 41
Mean 77.0 72.0 71.0 1.64 1.51 1.21 50.0 49.8
Significance P<0.05
IV
11 84 82 82 2.90 2.86 2.73 29 29
17 84 77 75 2.42 1.90 1.46 35 40
18 72 58 71 2.13 1.83 2.27 34 31
20 85 69 65 1.74 1.46 1.27 49 47
22 74 67 69 3.58 2.43 2.64 22 27
Mean 79.8 70.6 72.4 2.56 2.10 2.07 33.7 35.0
Significance P<0.05 P < 0.05
Perfusion pressure — mean arterial minus mean hepatic venous pressure; SBF = splanchnic blood flow; SVR =
splanchnic vascular resistance (perfusion pressure/splanchnic blood flow); Qo2 = splanchnic oxygen consumption, ?yo2 =
hepatic venous oxygen tension; RQ = respiratory quotient; and others as in Table 1.

The indocyanine green dye clearance technique
estimates hepatic blood flow directly since the
liver is the only organ capable of removing the
dye from the circulation. The metabolic measure-
ments, however, apply to the entire splanchnic
area, i.e. those viscera (liver, stomach, pancreas,
gallbladder, small intestine, large intestine above
the sigmoid colon and spleen) from which venous
drainage eventually enters the hepatic vein.
Following the control period, the first 5 subjects
were given propranolol1 (0.13 mg/kg iv) over a
10-min period after which the measurements de-
tailed above were repeated. Five other individuals
iKindly supplied by Dr. Sahagian-Edwards of
Ayerst Laboratories.
received 300 ml of 10* glucose solution (one half
as a rapid intravenous infusion and the remainder
slowly during the remainder of the study). Five
subjects received hexamethonium (0.5 mg/kg in
divided doses). A final 5 subjects were given phen-
oxybenzamine (0.7 mg/kg) by an infusion dur-
ing a 20-min period followed by a 40-min wait
(to permit maximal action of the drug to occur).
In addition, all subjects received approximately
200 ml of 0.9* NaCl solution to replace blood
taken in sampling. The dose of propranolol se-
lected is the same as that used in our previous
study (1); that of phenoxybenzamine was the
largest amount which could be tolerated consis-
tently without the occurrence of fainting. The last
15 individuals were subjected to three study
periods, namely, (1) control, (2) following treat-
CtrcvUtion Rtsurcb, Vol. XXI, September 1967

Downloaded from http://circres.ahajournals.org/ by guest on March 8, 2015

 CONTROL OF THE SPLANCHNIC CIRCULATION 337

Qo, (mj/min) P TOJ (mm Hg) RQ

EJ c Ei Ei c Ei Ei C Ei Ei

75 62 34 33 0.00 0.10
65 64 42 45 0.59 0.17
84 70 41 43 0.42 0.55
84 63 43 43 -0.75 0.23
46 41 39 34 0.50 0.74
70.6 60.0 39.8 39.6 -0.09 0.36
P < 0.05 P < 0.05

36 44 45 37 45 44 49 -0.16 0.00 0.00

67 72 71 59 37 34 43 0.48 0.75 0.68
47 122 76 66 49 42 43 0.61 0.65 0.51
51 53 63 41 44 48 48 0.40 0.65 0.41
67 48 48 44 41 42 42 0.12 0.42 0.19
53.6 67.8 60.4 49.3 41.5 41.9 44.9 0.29 0.49 0.36
P < 0.05 P < 0.05 P<0.05 P<0.05

57 72 71 60 41 40 37 0.46 0.58 0.51

59 62 77 55 46 37 40 0.37 0.20 0.83
62 42 50 40 45 46 45 0.13 0.13 0.62
68 61 53 56 37 39 38 0.40 0.49 0.69
52 49 69 50 49 45 46 0.11 0.86 0.58
59.4 57.1 63.9 52.2 43.6 41.3 41.1 0.29 0.45 0.65
P < 0.05 P < 0.05

30 68 64 61 52 56 56 -0.51 -2.01 -1.14

52 81 46 45 44 44 41 -0.14 -0.17 -0.01
32 72 48 70 41 43 38 0.50 -0.08 0.30
51 68 88 69 40 36 36 0.04 0.36 0.68
26 74 82 55 49 42 46 0.46 0.84 0.26
38.1 72.5 65.5 60.0 45.5 44.0 43.3 0.07 -0.21 0.02

ment with glucose, hexamethonium or phenoxy-
benzamine and (3) after administration of
propranolol. This sequence was followed to deter-
mine both the effects of glucose, hexamethonium
or phenoxybenzamine and any modification of the
response to propranolol which the previous treat-
ment might effect.
The data were analyzed for statistical signifi-
cance using paired f-tests where applicable (Ta-
bles 1 and 2); for unpaired data a nonpaired
f-test was used (Table 3).
Results
The principal results are shown in Tables
1 and 2. In Table 2 each value for flow, re-
sistance, and perfusion pressure is an average
of three individual determinations. In brief,
the administration of propranolol to the fast-
CircuUtion Resttrch, Vol. XXI, Stfumbtr 1967
ing subjects (group I) was followed by a
reduction in splanchnic blood flow, oxygen
consumption, and indocyanine green dye
clearance. Heart rate also was reduced. Cal-
culated splanchnic vascular resistance in-
creased, as did the splanchnic respiratory
quotient, but perfusion pressure (mean ar-
terial minus mean venous) was unaltered.
Cardiac output was reduced in 4 of 5 sub-
jects.
An infusion of glucose (group II) had no
apparent effect, except to increase respira-
tory quotient, and the subsequent administra-
tion of propranolol caused the same direc-
tional changes as in the absence of previous
treatment with glucose, except that respira-

Downloaded from http://circres.ahajournals.org/ by guest on March 8, 2015

338
TABLE 3
Effect of Previous Treatment on Changes following Propranold Administration
SBF (liter/into) SVR (mm Hg'Hterper per min)
None Cyclo PBZ None
Previous treatment
Initial value 1.65 1.29 1.51 54
After propranolol 1.17 0.61 1.21 77
Change 0.48 0.68 0.30 23
SE 0.11 0.13 0.07 5 14
Significance P<0.05 P<0.05
Abbreviations: Cyclo = subjects anesthetized with cycloproprane; PBZ = subjects who had previous treatment
with phenoxybenzamine; others as in Table 2.
Significance: referred to control.
tory quotient did not increase further in re-
sponse to the blocking agent. Comparison of
the magnitude of the various responses to
propranolol showed no other significant dif-
ference depending upon previous treatment
except that the increase in splanchnic vascu-
lar resistance was less (P<0.01).
Phenoxybenzamine (group III) had no
apparent initial effect except to increase heart
rate. It apparently altered the response to
propranolol as follows: (1) the respiratory
quotient was still increased, but no longer
consistently so, (2) the increase in splanch-
nic vascular resistance was smaller (P <
0.001), and (3) the reduction in blood flow
was less (P<0.05).
In contrast, hexamethonium pretreatment
(group IV) apparently prevented all of the
actions of propranolol that were observed in
the untreated subjects and in those who re-
ceived either the glucose or the phenoxy-
benzamine pretreatment. The direct actions
of hexamethonium were to reduce splanchnic
indocyanine green dye clearance, perfusion
pressure, and blood flow.
In no subject was an elevated concentra-
tion of a catecholamine detected in arterial
plasma; the levels in the fasting subjects
ranged from zero to 0.12 fig/liter epinephrine
and from zero to 0.48 /Ag/liter norepineph-
rine. Pao2 ranged from 73 to 107 mm Hg and
Paco2 from 34 to 45 mm Hg. Arterial glucose
concentrations ranged from 76 to 110 mg per
100 ml of blood before treatment and were
unaffected by hexamethonium, phenoxybenza-
Downloaded from http://circres.ahajournals.org/ by guest on March 8, 2015
PRICE, COOPERMAN, WARDEN
PTOI t(mm Hg)
Cyclo PBZ None Cyclo PBZ
80 50 40 44 41
133 60 40 28 41
53 10 0 16 0
3 1.2 3.2 1.3
p <0.01 P < 0.01 P < 0.001
mine, or propranolol. During glucose admin-
istration the concentration in arterial blood
averaged 147 mg per 100 ml of blood. The
hepatic extraction of indocyanine green dye
was unaltered by any of the drugs which were
administered or by glucose.
Discussion
These results suggest that the splanchnic
vasculature in man is influenced by sympa-
thetic nerves which contain vasodilator as
well as vasoconstrictor fibers, or by identical
fibers which have both effects, depending
upon whether a- or /J-receptors are activated.
Our evidence for this is as follows:
First, propranolol is an exceptionally spe-
cific /3-receptor blocker and is apparently de-
void of direct sympathomimetic or vascular
actions (8, 9). Among its effects in this study
were an increase in splanchnic vascular re-
sistance and a reduction in blood flow and
oxygen consumption. The present results
(group IV) support the conclusion that these
actions depend upon the presence of tonic
sympathetic nervous activity, (i.e. are not
caused by nonspecific drug actions). A pos-
sible exception to this statement would occur
if propranolol, like certain a-receptor block-
ing agents, interfered with the uptake and
restorage of the norepinephrine liberated up-
on the arrival of nervous impulses at sym-
pathetic nerve terminals. This possibility has
not yet been examined, but it is believed to
be unlikely.
Second, propranolol can exert its effect in
CiraiUtio* Rtstarcb, Vol. XXI, Sfpttmttr 1967
CONTROL OF THE SPLANCHNIC CIRCULATION
the presence of a-receptor blockade. Al-
though we have no proof that a-receptor
blockade was total and complete this finding
apparently rules out the possibilities that pro-
pranolol acts only directly (via a-receptor
stimulation) or that it acts only reflexly (via
increased a-adrenergic nervous activity).
Third, there was no detectable level of
epinephrine in the plasma of our subjects. The
method used can detect a concentration of
0.1 /ig/liter in plasma which corresponds to
a secretion rate of about 0.1 /tg/min, an
amount believed to be physiologically insig-
nificant (10). The rate at which norepineph-
rine is secreted from the adrenal medulla in
resting man is also believed to be physiologi-
cally insignificant (10) and, moreover, the ef-
fect of infusing norepinephrine intravenously
is to cause splanchnic vasoconstriction, not
dilatation (11). The effect of giving propran-
olol consequently could not have depend-
ed upon blocking an action mediated via cir-
culating catecholamines.
Although a-receptor blockade did not sup-
press the response of the splanchnic vascula-
ture to propranolol, it did reduce it, and this
would favor either the existence of a tonical-
ly active sympathetic vasoconstrictor pathway
in our subjects at rest or the reflex activation
of a-receptors by propranolol. It is interesting
that in the previous study (1) performed in
5 anesthetized subjects, who had an abnor-
mally elevated level of sympathetic tone, the
administration of propranolol caused a
significantly greater increase in splanchnic
vascular resistance than it did in the present
investigation. Table 3 compares the effects
of propranolol on splanchnic vascular re-
sistance, splanchnic blood flow and venous
oxygen tension in three groups of individuals
studied by us who (presumably) had differ-
ent initial levels of sympathetic tone. The
data recorded during administration of cyclo-
propane were obtained in an earlier study
(1), but have not previously been fully re-
ported. The increase in resistance on giving
propranolol is significantly augmented by cy-
cloproprane administration and reduced by
previous treatment with phenoxybenzamine.
CircuUtio* Rtis+rcb, Vol. XXI, Sepltmbtr 1967
Downloaded from http://circres.ahajournals.org/ by guest on March 8, 2015
339
These differences are reflected in quantitative-
ly similar reductions in splanchnic blood flow.
It is of interest that the hepatic venous oxy-
gen tension, while insignificantly affected by
propranolol in fasting, conscious subjects, was
conspicuously diminished in those receiving
cyclopropane to a mean level approximat-
ing 30 mm Hg. From the standpoint of
splanchnic oxygen availability, it may be un-
wise to administer a y8-receptor blocking
agent when sympathetic nervous outflow is
augmented.
The existence of both a- and /3-recep-
tors in the splanchnic viscera could also
explain the curious result (12) that hemor-
rhage, although undoubtedly increasing sym-
pathetic nervous activity, may not increase
splanchnic vascular resistance. Although it is
stated that sympathetic vasodilator fibers do
not supply the splanchnic viscera (13, 14)
the evidence for this statement is not con-
vincing.
Since the vasodilator effects of y3-receptor
activation are accompanied by metabolic al-
terations, we were not surprised to find that
the increase in splanchnic vascular resistance
caused by propranolol was accompanied by
metabolic changes. In particular, ^-receptor
blockade resulted in a reduced splanchnic
oxygen consumption and an increased re-
spiratory quotient. Splanchnic oxygen ex-
traction and the Po^ of hepatic venous blood
in our normal, unanesthetized subjects were
unaltered by propranolol, suggesting that the
reduction in splanchnic blood flow resulted
from a quantitatively similar diminution in
oxygen demand.
It has been estimated that roughly 80* of
the oxygen consumed by the liver is used to
oxidize free fatty acids (15). Since the rate
at which free fatty acids are oxidized depends
directly upon their concentration in plasma
(16), it is not unreasonable to expect that an
agent, such as propranolol, which blocks the
mobilization of free fatty acids (17, 18) will
reduce hepatic oxygen consumption. In addi-
tion, the presence of circulating free fatty
acids causes inhibition of pyruvate kinase,
thus leading to gluconeogenesis (19). For this
340
reason the hepatic respiratory quotient should
be reduced by the presence of free fatty acids
and increased by any inhibition of free fatty
acid mobilization. Thus, not only the circula-
tory, but also the metabolic, effects of propran-
olol may best be explained as consequences of
the interruption of a tonic /} activity.
With respect to the low splanchnic re-
spiratory quotient values that we observed, our
results resemble those of Rowell and co-work-
ers (20). It is possible that ketosis accounts
in part for this finding, since the formation
of ketones from free fatty acids requires oxy-
gen but does not produce carbon dioxide. The
effects of glucose and propranolol on this
ratio were those to be expected. We cannot
explain the occasional apparent uptake of
carbon dioxide by the splanchnic viscera, a
phenomenon also noted by Rowell et al.
References
1. PRICE, H. L., DEUTSCH, S., DAVIDSON, I. A.,
CLEMENT, A. J., BEHAR, M. C , AND EPSTEIN,
R. M.: Can general anesthetics produce splanch-
nic visceral hypoxia by reducing regional blood
flow? Anesthesiology 27: 24, 1966.
2. PRICE, H. L., DEUTSCH, S., COOPERMAN, L. H.,
CLEMENT, A. J., AND EPSTEIN, R. M.: Splanch-
nic circulation during cyclopropane anesthesia
in normal man. Anesthesiology 26: 312, 1965.
3. CAESAR, J., SHALDON, S., CHIANDUSSI, L., GUE-
VARA, L., AND SHERLOCK, S.: Use of indocya-
nine green in the measurement of hepatic blood
flow and as a test of hepatic function. Clin.
Sci. 21: 43, 1981.
4. NIELSEN, N. C : Spectrophotometric determina-
tion of indocyanine green in plasma especially
with a view to an improved correction for
blank density. Scand. J. Clin. Lab. Invest. 15:
613, 1963.
5. VAN SLYKE, S. D., AND NETLL, J. A.: Determina-
tion of gases in blood and other solutions by
vacuum extraction and manometric measure-
ments. J. Biol. Chem. 61: 523, 1924.
6. BERCMEYER, H., AND BERNT, E.: D-glucose. De-
termination with glucose oxidase and peroxi-
dase. In Methods of Enzymatic Analysis, edited
20.
by H. Bergmeyer. New York, Academic Press,
1963.
7. PRICE, H. L., AND PRICE, M. L.: Chemical estima-
tion of epinephrine and norepinephrine in hu-
Downloaded from http://circres.ahajournals.org/ by guest on March 8, 2015
PRICE, COOPERMAN, WARDEN
man and canine plasma. II. A critique of the
trihydroxyindole method. J. Lab. Clin. Med.
50: 769, 1957.
8. SHANKS, R. G.: Pharmacology of beta sympa-
thetic blockade. Am. J. Cardiol. 18: 308, 1966.
9. BRICK, I., GLOVER, W. E., HUTCHISON, K. J.,
AND RODDA, I. C : Effects of propranolol on
peripheral vessels in man. Am. J. Cardiol. 18:
329, 1966.
10. PRICE, H. L.: Circulating adrenaline and nor-
adrenaline during diethyl ether anaesthesia in
man. Clin. Sci. 16: 377, 1957.
11. BEARN, A. C , BUXTNG, B., AND SHERLOCK, S.:
Effect of adrenaline and noradrenaline on
hepatic blood flow and splanchnic carbohy-
drate metabolism in man. J. Physiol. (London)
115: 430, 1951.
12. PRICE, H. L., DEUTSCH, S., MARSHALL, B. E.,
STEPHEN, G. W., BEHAR, M. G., AND NEU-
FELD, G. R.: Hemodynamic and metabolic
effects of hemorrhage in man, with particular
reference to the splanchnic circulation. Circu-
lation Res. 18: 469, 1966.
13. UVNAS, B.: Central cardiovascular control. In
Handbook of Physiology, sec. I, vol. 2. Wash-
ington, D. C , American Physiological Society,
1960, p. 1136.
14. GHAYSON, J., AND MENDEL, D.: Physiology of the
Splanchnic Circulation. Baltimore, Williams and
Wilkins, 1965, p. 91.
15. LUNDQUIST, F.: Metabolism of carbohydrates in
the normal liver and under the influence of
ethanol and hormones. Scand. J. Lab. Clin.
Invest. 18 (suppl. 92): 47, 1966.
16. STEINBERG, D.: Catecholamine stimulation of fat
mobilization and its metabolic consequences.
Pharmacol. Rev. 18: Parti, 217, 1966.
17. NAKANO, J., KUSAKARI, T., AND BERRY, J. L.:
Effects of propranolol on the circulatory
changes and mobilization of free fatty acids
by isoproterenol. Arch. Intern. Pharmacodyn.
164: 120, 1966.
18. Mum, G. G., CHAMBERLAIN, D. A., AND PEDOE,
D. T.: Effects of /9-sympathetic blockade on
non-esterified-fatty-acid and carbohydrate me-
tabolism at rest and during exercise. Lancet
1: 930, 1964.
19. WEBER, G., CONVERY, H. J. H., LEA, M. A.,
AND STAURM, N. B.: Feedback inhibition of
key glycolytic enzymes in liver: action of free
fatty acids. Science 154: 1357, 1966.
ROWELL, L. B., KRANING, K. K., EVANS, T. O.,
KENNEDY, J. W., BLACKMAN, J. R., AND KU-
SUMI, F.: Splanchnic removal of lactate and
pyruvate during prolonged exercise in man.
J. Appl. Physiol. 21: 1773, 1966.
OrcuUtion Rtiarcb, Vol. XXI, Stpttmbtr 1967
 Control of the Splanchnic Circulation in Man: ROLE OF BETA-ADRENERGIC
RECEPTORS
HENRY L. PRICE, LEE H. COOPERMAN and JOHN C. WARDEN

Circ Res. 1967;21:333-340

doi: 10.1161/01.RES.21.3.333
Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1967 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7330. Online ISSN: 1524-4571

The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circres.ahajournals.org/content/21/3/333

Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the
Editorial Office. Once the online version of the published article for which permission is being requested is
located, click Request Permissions in the middle column of the Web page under Services. Further information
about this process is available in the Permissions and Rights Question and Answer document.

Reprints: Information about reprints can be found online at:

http://www.lww.com/reprints

Subscriptions: Information about subscribing to Circulation Research is online at:

http://circres.ahajournals.org//subscriptions/

Downloaded from http://circres.ahajournals.org/ by guest on March 8, 2015