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Clinical Science ( 1990)79,13 1-1 38
131
Haemodynamic and metabolic effects of infused adenosine in
man
ANDERS EDLUND', ALF SOLLEVI* AND BIRGITTA LINDE'
'Department of Clinical Physiology, Huddinge and Karolinska Hospital, Huddinge, and *Departmentof Anaesthesiology,
Sodersjukhuset, Stockholm, Sweden
(Received 31 January 1990; accepted 23 March 1990)
SUMMARY
1. Haemodynamic and metabolic effects of intravenous infusion of adenosine, an endogenous vasodilator,
were studied in healthy humans.
2. Catheters were inserted into pulmonary and
brachial arteries and into the hepatic and subclavian
veins. Cardiac output was determined according to the
Fick principle, and splanchnic blood flow was measured
by using extraction of Indocyanine Green. Skin blood
flow was estimated by a laser Doppler technique, calf
blood fiow by venous occlusion plethysmography and
skeletal muscle and adipose tissue blood flow by a local
isotope clearance technique.
3. Adenosine (infused in steps from 40 to 80 pg min-'
kg- into a central vein) elicited a gradual reduction in the
peripheral vascular resistance to less than 50% of the
basal level. There was a slight increase in the systemic
blood pressure, but the pulmonary arterial and the
ventricular filling pressures were unchanged. Cardiac
output was doubled, accomplished by a combination of a
positive chronotropic effect and an increase in stroke
volume, which may be secondary to diminished
peripheral resistance.
4. Skin blood flow increased by 100% at 50 pg of
adenosine min-' kg-', whereas splanchnic blood flow
rose sigmficantly at 60 ,ug of adenosine min-' kg-'.
Blood flow in the calf, gastrocnemius muscle and adipose
tissue did not change significantly.
5. Arterial concentrations of noradrenaline and
adrenaline increased by 62 and 43%, respectively, during
infusion of adenosine. Arterial levels of glycerol were
depressed by more than 50%, but those of glucose and
pyruvate were unchanged.
6. In conclusion, exogenous adenosine caused a
marked systemic vasodilatation, with different responsiveness in the investigated vascular beds. The vasodilata-
'
Correspondence: Dr Anders Edlund, Department of Clinical
Physiology,Karolinska Hospital, S- 10401 Stockholm,Sweden.
tion occurred in the presence of an increase in generalized
sympathetic activity. Adipose tissue blood flow was
unaltered despite a considerable reduction in fat
mobilization.
Key words: adenosine, cardiac output, catecholamines,
glycerol, regional circulation.
INTRODUCTION
Adenosine is mainly formed by dephosphorylation of 5'adenosine triphosphate or hydrolysis of S-adenosylhomocysteine [l, 21. Due to cellular uptake and
enzymatic degradation, adenosine is effectively eliminated
from the blood in humans with a half-life of less than 10 s
[31.
The cardiovascular effects of adenosine were first
recognized in 1929 by Drury & Szent-Gyorgyi [4], who
reported a general vasodilator effect and negative
inotropic, chronotropic and dromotropic effects in the
isolated heart. Later, adenosine has been demonstrated to
dilate most vascular beds: in heart [S], skeletal muscle [6,
71, intestine [8]and brain [9, 101. The renal circulation
may be an exception as transient vasoconstriction has
been reported in the dog [ 111. Adenosine also has a wellknown anti-lipolytic effect in animals [ 12, 131. In nervous
tissue adenosine antagonizes neurotransmission [ 14, 151,
but in man there are reports of increased or unchanged
levels of circulating catecholamines [16, 171. Depending
on the dose and mode of administration, both bradycardia with atrioventricular-block (bolus administration)
[18, 191 and tachycardia [17, 201 have been reported in
man. Systemic infusion of low doses of adenosine to
healthy man caused a minor increase in cardiac output,
paralleled by a decrease in peripheral vascular resistance,
the arterial blood pressure being unchanged [21]. To what
extent different vasculatures were dilated was not
analysed.
Thus, knowledge of the effects of adenosine mostly
derives from isolated tissues or from experiments in intact
132
A. Edlund et al.
animals, with relatively few studies of the effects in man.
Information about regional circulatory effects as well as
metabolic effects of adenosine in humans is of
importance, since the compound has been recently introduced as a vasodilator compound in different clinical situations [7, 221. The aim of the present study was therefore
to investigate in conscious healthy humans the effects of
intravenous adenosine, up to the highest tolerable dose,
on central and regional haemodynamics as well as on
some metabolic variables.
METHODS
Subjects
Ten healthy volunteer subjects, six women and four
men, aged 20-35 years, were investigated. Their heights
and weights averaged 172 4 cm and 63 k 3 kg, respectively. The investigation was approved by the Ethics
Committee of Huddinge Hospital.
*
Procedure
The subjects reported to the laboratory in the morning
after an overnight fast, including more than 12 h without
tobacco and coffee (or other xanthine-containing
beverages). With the subject resting in the supine position,
a double-lumen Swan-Ganz catheter was introduced
percutaneously into a right antecubital vein and advanced
under fluoroscopical control to a position with the tip in
the pulmonary artery. A Cournand catheter no. 6 was
similarly inserted into a hepatic vein through the right
femoral vein. Thin polyethylene catheters were introduced into the brachial artery and subclavian vein.
After a resting period of 60 min, infusion of adenosine
into the subclavian vein was started at a rate of 40 pg
min-' kg- Every 20 min the infusion rate was increased
by 10 pg min-' kg-' to a final dose of 80 pg min-l kg-I.
Due to side-effects, not all subjects tolerated the highest
infusion rates.
'.
Haemodynamic measurements
Heart rate was monitored continuously by a one-lead
electrocardiograph. Blood pressure was registered after
16-18 min at each infusion rate in the brachial and
pulmonary arteries and the right atrium.
Peripheral resistance was calculated as
Mean arterial pressure - right atrial pressure
cardiac output
according to the Fick principle by sampling expired air
for 5 min (once during basal conditions and once at each
infusion step after 15-20 min of infusion), calculating
oxygen uptake and measuring the systemic
arterial-pulmonary arterial oxygen concentration difference (blood samples taken at start and end of air
sampling, using the mean value for further calculation).
Splanchnic blood flow was measured by extraction
(arterial-hepatic vein content) of Indocyanine Green [24,
251 basally and every 5 min at each rate of adenosine
infusion. A laser Doppler probe, connected to a flowmeter (Periflux; Perimed AB, Stockholm, Sweden [26]),
was attached to the skin just below the middle of the
clavicle for continuous recording of relative skin blood
flow. The flowmeter gives a linear response both to
velocities and flux of erythrocytes [27, 281. Flow is
expressed as a percentage of the basal value. However, a
portion of the instrument signal has its origin in internal
tissue motion other than blood flow. Thus, the percentage
change in flow signal underestimates the true changes in
blood flow.
Adipose tissue blood flow was measured continuously
by clearance of locally injected 133Xe[29, 301 after
bilateral injection of 40 kBq into the abdominal subcutaneous fat. Calf blood flow was determined basally and
every 5 min during adenosine infusion by venous occlusion plethysmography as described by Dohn [31], using a
distal arterial occlusion to exclude foot circulation.
Muscle blood flow was followed in the gastrocnemius
muscle in the contralateral leg by the local 133Xeclearance
technique [32] after injection of 400 kBq of isotope. Since
the disappearance rate from muscle was multi-exponential, it was compared with a control study, performed
in another eight healthy subjects, who were not subjected
to infusion of adenosine. Blood flow in the adipose tissue
and the calf is expressed in ml s - I 1- tissue volume.
Blood samples for determination of lactate, pyruvate,
glycerol (arterial and hepatic venous), adrenaline and
noradrenaline (arterial) were taken basally and at each
infusion step after 16-1 8 min of infusion.
'
Analytical procedures
The oxygen content in blood was analysed according to
standard procedures. Adrenaline and noradrenaline were
analysed by using h.p.1.c. with electrochemical detection
[33]. Lactate, pyruvate and glycerol were determined
fluorimetrically as described elsewhere [34, 351. Glucose
was analysed in deproteinized plasma with a Glucose
Analyzer (Beckman;Palo Alto, CA, U.S.A.).
and pulmonary resistance as
Data analysis
Mean pulmonary arterial pressurepulmonary capillary venous pressure
No statistically significant differences were found
between determinations made at different times during
each infusion step, which is in accordance with the steadystate level of cardiac output and peripheral resistance
observed during 15 min of infusion of adenosine by Bush
et al. [21]. Therefore, the mean values for each period
were used for further calculations and presentations.
cardiac output
When missing (in five subjects), the pulmonary capillary
venous pressure was replaced by the diastolic pulmonary
arterial pressure (cf. [23]).Cardiac output was determined
Haemodynamic effects of intravenous adenosine
Statistics
Results are means fSEM. For calculation of statistical
differences, one-way analysis of variance with the Fisher
test was used.
but increased markedly at higher infusion rates (Table 1,
Fig. 3),being almost doubled at the highest rate.
The basal skin blood flow showed small oscillations
around a stable mean level. During infusion the mean
RESULTS
The basal uptake of oxygen was 2 1 8 f l l ml/min.
Infusion of adenosine did not significantly alter the
consumption of oxygen, which measured 243 f 16 ml/
min at the highest infusion rate. The respiratory Guotient
and ventilatory volume did not change significantly from
the basal values (0.80 f 0.03 and 7.3 f0.2 I/min, respectively) during infusion of adenosine. All subjects experienced symptoms such as cutaneous flushing, chest
oppression, palpitations, headache, abdominal pain or
anxiety. Due to these sensations only five subjects
accepted the dose of 80 pg min-' kg-I.
133
SVR
2olT
Central haemodynamics
Cardiac output displayed a gradual, marked increase
during adenosine infusion (Fig. l), being twice the basal
output at the highest infusion rate (5.0f 0.3 and 9.6 f0.7
I/min, respectively). Heart rate increased gradually from
6 0 f 2 beats/min, reaching a maximum of 9 0 f 6 beats/
min at 80 p g of adenosine min-' kg-I (Fig. 2). Stroke
volume increased at the lowest infusion rate with a only
minor further increase at higher infusion rates (Fig. 2). As
a consequence of the increased cardiac output, during
unchanged whole body oxygen uptake, the arterialpulmonary artery concentration difference for oxygen
decreased markedly, from 44 f 2 ml/l in the basal state to
2 6 f 2 ml/l at an infusion rate of 80 pg of adenosine
min- kg - I (P<0.00 1), indicating a hyperkinetic circulation.
Systolic blood pressure and pulse pressure amplitude
showed gradual increases from 1 2 9 f 3 and 5 9 f 3
mmHg, respectively, to 1 4 2 f 5 and 8 3 f 4 mmHg
( P < O . O l and 0.001, respectively) at 80 pg of adenosine
min-' kg-I, whereas diastolic pressure did not change
sigdicantly ( 6 9 f 2 and 6 0 f 3 mmHg, respectively).
Mean arterial pressure was not sigmficantly altered.
Pulmonary artery pressure (21 f 1 mmHg systolic, 9 f 1
mmHg diastolic), right atrial pressure (5f 1 mmHg) and
pulmonary capillary venous pressure (9 f 1 mmHg) did
not change.
During infusion there was a gradual decrease in the
systemic vascular resistance, amounting to more than
50% at the highest infusion rates (Fig. 1).The decrease in
pulmonary vascular resistance, from the basal level of
0.7f0.1 to 0.5f0.1 mmHg min-' I-' at the highest
infusion rate, did not reach statistical significance.
Basal
I
I
I
I
i
40
50
60
70
80
Adenosine (pgmir-' kg-')
Fig. 1. Cardiac output (CO) and systemic vascular
resistance (SVR) in the basal state and during infusion of
adenosine (40-80 pg min-' kg-l intravenously).
Statistical sigmficance:*P< 0.05, **P< 0.01, ***PC 0.001
compared with basal. Values are means f SEM.
120
80
40
"
1
HR
I
I
I
I
I
I
Basal
40
50
60
70
80
Adenosine (pg mir-'kg-')
Peripheral haemodynamics
The basal blood flow in the splanchnic region
measured 1.4 f 0.1 I/min. Flow remained unchanged at
infusion rates of 40 and 50 pg of adenosine min-' kg-I,
Fig. 2. Stroke volume (SV) and heart rate (HR) in the
basal state and during infusion of adenosine (40-80 pg
&-I
kg- intravenously). Statistical significance:
*P<0.05, **P< 0.01, ***P< 0.001 compared with basal.
Values are means f SEM.
134
A. Edlund et al.
amplitude of the Doppler signal was doubled at an
infusion rate of 50 pg of adenosine min-l kg-' (Table 1,
Fig. 3) and the oscillations were magnified (Fig. 4).
Furthermore, even at the lowest infusion rate there were
repeated blood flow peaks of variable magnitude,
amounting at most to twice the mean level and lasting a
few minutes each (a typical response is shown in Fig. 4).
After discontinuation of the infusion of adenosine, skin
blood flow gradually returned towards the basal level,
which was not reached until after 10-20 min. This is in
contrast to other effects of adenosine, such as the increase
in heart rate and the subjective symptoms (e.g. chest
oppression, abdominal discomfort), which disappeared
within a few minutes.
Blood flow in the adipose tissue and the calf (plethysmographic measurement) did not change significantly
during adenosine infusion (Table 1).The disappearance
curves for 133Xefrom the gastrocnemius muscle during
adenosine infusion and control were congruent, suggesting that there was no change in muscle blood flow during
these doses of adenosine infusion.
Metabolic variables
The arterial concentrations of glycerol showed a
gradual decrease (Table 2), whereas those of pyruvate,
lactate and glucose were unchanged. The hepatic
exchange of these metabolites did not show any significant changes, except for a transient increase in lactate
uptake (Table 2).
Arterial plasma catecholamines
From a basal level of 0.90 f 0.15 nmol/l, arterial noradrenaline increased and reached 1.46 f0.18 nmol/l at
the highest infusion rate (Table 2). Arterial adrenaline was
slightly elevated already in the basal state, measuring
0.53 f 0 . 1 2 nmol/l, but increased further during adenosine infusion, reaching a maximal level of 0.75f0.18
nmol/l at 60 pg of adenosine min- I kg- I (Table 2).
DISCUSSION
This investigation is the first to present data on simultaneous central and regional haemodynamic responses to,
as well as some metabolic effects of, systemic adenosine
administration in healthy volunteers. Previous studies in
conscious subjects have only examined the influence of
adenosine on systemic blood pressure, heart rate [ 17,201
and central haemodynamics [211.
Central haemodynamics
The stepwise increase in the adenosine infusion rate
from 40 to 80 pg min-' kg-I was associated with a dosedependent decrease in peripheral vascular resistance to a
value as low as half the basal one at the highest dose level.
This vasodilatation was accompanied by a major increase
in cardiac output, which was doubled at 80 pg of adenosine min-l kg-l. The systemic blood pressure was only
slightly affected, showing a minor increase in systolic
pressure and pulse pressure at the higher infusion rates.
The maintenance of the systemic blood pressure and the
increased heart rate in our conscious volunteers is in
agreement with previous clinical investigations [ 17, 20,
2 11. The systemic vasodilatory effect of adenosine (reduction in systemic vascular resistance) is thus paralleled by a
reflex increase in cardiac output, resulting in unaffected
mean arterial blood pressure with increased pulse
pressure. This is in contrast to the effects during
anaesthesia, when infusion of adenosine causes dosedependent hypotension, due to an inadequate reflex
increase in cardiac output [16, 361. Furthermore, in
patients with sympathetic autonomic dysfunction,
infusion of adenosine causes reduction in blood pressure,
supporting the view that baroreceptor activation is
involved in the maintenance of blood pressure during
intravenous administration in conscious healthy subjects
~71.
In the present study, the responses of heart rate and
blood pressure were of the same magnitude as those in the
study of Biaggioni et af. [17], although our maximal
infusion rate was only 80 pg min-l kg-l as compared
with 140 pg min-' kg- in the latter study. Bush et af. [21]
found less pronounced effects on peripheral vascular
resistance and heart rate than those seen in this study at a
comparable dose level. These discrepancies in the
reported effects of adenosine may be explained by the
different sites of infusion. Due to the extremely rapid
inactivation of adenosine in the circulation (half-life less
than 10 s [3]), a more peripheral venous infusion site
results in more degradation before the arterial circulation
is reached.
Table 1. Blood flow in the splanchnic region (dye extraction), the skin (laser Doppler technique), the calf (venous
occlusion plethysrnography) and in the abdominal subcutaneous fat (isotope clearance) during infusion of adenosine
(40-80 pg min- kg- intravenously) in healthy subjects
Values are means fSEM.Statistical significance: *P< 0.05, **P< 0.01, ***P< 0.001 compared with basal.
Dose of adenosine (pgmin
~
I
kg- I ) .
..
Basal
( n= 10)
Splanchnic blood flow (l/min)
1.40 f0.13
Skin blood flow (arbitrary units)
23f3
Calf blood flow (mls - I I - ' )
0.24f0.02
Adiposetissuebloodflow(mls-'l-~) 1.2fO.2
( n = 10)
40
50
( n= 10)
60
( n=9)
1.46 f 0.14
33+6
0.24f0.02
1.3f0.2
1.50 k0.18
50 f 16*
0.23+0.03
1.3 f 0.2
1.97+0.33*
4 8 f 12*
0.23f0.03
1.4f0.3
70
( n =6)
2.22 f 0.52**
48 f 12*
0.20f0.03
1.3f0.2
80
( n= 5 )
2.18 f 0.38***
46+11*
0.17 f 0.03
1.1 f 0 . 2
Haemodynamiceffects of intravenousadenosine
The increase in cardiac output was accomplished by a
combined elevation of stroke volume and heart rate. The
increase in stroke volume may be due primarily to the
decrease in peripheral resistance. Whether or not changes
in inotropy also contributed cannot be determined from
the present study. Adenosine-induced enhancement in
*
*
*-
T
T
*
135
inotropy has not been reported, but in isolated hearts
adenosine exerts negative inotropic effects in the atria
[37].Since the end-diastolic volumes were not measured,
one cannot tell whether an increased preload may have
contributed to the increase in stroke volume, but the
ventricular f i i g pressures (right atrial pressure, diastolic
pulmonary artery pressure and pulmonary capillary
venous pressure) were not affected. The positive chronotropic response to adenosine infusion has been suggested
to be caused by a combination of vagal withdrawal and
sympathetic activation [20].The latter is indicated in our
study by the slightly elevated levels of circulating noradrenaline. It is worth noting that in vitro and after bolus
injections in humans, adenosine exerts dose-dependent
and transient (seconds)negative chronotropiceffects [ 181.
The discrepancy between the present situation in vivo on
the one hand and previous bolus injections in vivo and
studies in vitro on the other hand could possibly be
explained by the much higher adenosine concentrations
that were reached in the latter situations and the lack of
reflex adjustmentsin those cases.
Splanchnic
Peripheral haemdynamics
-100
-+
Basal
I
I
I
I
40
50
60
70
I
80
Adenosine (pg min- kg- I )
Fig. 3. Percentage change in blood flow in the skin and
the splanchnic region during infusion of adenosine
(40-80 pg min- kg- intravenously).Statistical significance: *P<0.05, **P< 0.01, ***P< 0.001 compared with
basal. Values are means f SEM.
'
.I
100,
$ 1
0 1 /-
'
1 min
Basal
Infusion of adenosine
Fig. 4. Skin blood flow, as measured by the laser Doppler
technique, in one healthy subject in the basal state and
during infusion of adenosine (80 pg min-' kg-' intravenously),showing a typical response. The basal flow was
low, with small oscillations.During adenosine infusion the
mean blood flow increased, the oscillations were greatly
magdied and peaks of high blood flow of a few minutes
duration occurred. Flow is expressed as a percentage of
the maximal response of the instrument.
The regional vascular effects of adenosine suggest that
the skin is the most sensitive of the four tissues studied.
This is illustrated by the fact that skin flow started to
increase at 40 p g of adenosine min-' kg-' and was
maximal at 50 pg of adenosine min-I kg-I, whereas
splanchnic flow did not increase until 60 pg of adenosine
min-' kg-l (Fig. 3). On the other hand, skeletal muscle
and adipose tissue did not show any vasodilatation at all
at adenosine doses of up to 80 pg min-' kg-I. The doseindependent and long-lasting effect of adenosine on skin
blood flow differs markedly from other cardiovascular
responses, e.g. the increases in heart rate and coronary
blood flow ([38];A. Edlund et al., unpublished work).We
therefore speculate that, in the skin, adenosine may
release some long-lasting vasodilator, possibly a peptide
such as calcitonin-gene-related peptide [39].
With respect to the different regional flow responses, it
is possible that the rapid elimination of adenosine causes
the plasma concentration during exogenous administration to be higher in arterial blood reaching a proximal
vascular bed, such as the coronary circulation, than in
more distal tissues. However, the transit time and,
consequently, the blood concentration of adenosine is
unlikely to differ much between three of the peripheral
tissues studied. the skin (thoracic region), adipose tissue
(abdomen)and the splanchnic area. Skeletal muscle blood
flow, on the other hand, was studied more peripherally
(the calf), and possibly the adenosine concentrations may
have been somewhat lower at the effector sites of the
vasculature in this tissue.
A rough estimate of the increases in blood flow in the
skin and splanchnic region cannot account for the total
increase in cardiac output. The cerebral [lo] and
coronary [ 5 ] vasculatures are also known to dilate in
response to adenosine infusion, but probably other
regions are dilated as well.
136
A. Edlund et al.
Sympathetic
activation
.
.
The plasma levels of catecholamines, especially noradrenline, were elevated during adenosine infusion,
indicating sympathetic activation. This is in contrast to
fiidings in vitro, where adenosine inhibits the release of
noradrenaline [14, 401. The increase in circulating noradrenaline in this study, in agreement with the findings of
Biaggioni et al. [17], indicates that sympathetic reflex
mechanisms overcome this possible inhibitory effect.
Increased sympathetic activity during adenosine infusion
in man has in fact been found by a direct recording
technique [41]. This sympathetic discharge may be
secondary to baroreceptor activation due to the pronounced peripheral vasodilatation, but an activation
through afferent myocardial receptors may also occur
[42]. This sympathetic reflex may thereby counteract a
direct vasodilating effect of adenosine. The vasculature in
skeletal muscle is indeed sensitive to the vasodilating
effect of adenosine, since a threefold increase in leg blood
flow has been demonstrated during
- local infusion of
adenosine into the femoral artery (19 pg/min or about 0.3
pg min-l kg-l) [43]. However, such infusion probably
provides higher local plasma concentrations of the drug
and possibly without enhancing sympathetic reflex
discharge to the leg tissues.
The feelings of discomfort experienced by the
volunteers at ;he highest dose(s) of adenosine may have
induced physiological effects by themselves. However,
although the rises in the catecholamine levels are of
similar magnitude, the haemodynamic and metabolic
response patterns during mental stress and adenosine
infusion are markedly different. Thus, despite the fact that
a considerable increase in cardiac output occurred during
intense mental stress, the reduction in the peripheral
resistance was less pronounced, and the systemic blood
pressure rose markedly [44]. Vasodilatation occurred
primarily in skeletal muscle and adipose tissue [45], which
were unaffected by adenosine. Furthermore, lipolysis
increased markedly during mental stress. In addition,
effects of adenosine were found at doses too low to elicit
any subjective discomfort. Therefore, it seems unlikely
that physiological stress factors would contribute sigmficantly to the haemodynamic and metabolic responses
found in this study.
Metabolic effects
Adenosine produces powerful anti-lipolytic effects in
animal models both in vitro and in vivo [ 12, 13, 461 and
has been proposed to be a physiological regulator of
Table 2. Arterial concentrations, arteriovenous concentration differences and splanchnic uptake of glycerol, pyruvate,
lactate and glucose, and arterial concentrations of adrenaline and noradrenaline, in the basal state and during infusion of
adenosine (40-80 c(g min- * kg- intravenously) in healthy subjects
Values are means f SEM.Statistical significance: *P< 0.05, **P< 0.01 compared with basal.
Dose of adenosine
(pgmin-l kg-l)...
Glycerol
Arterial concn. (pnol/l)
(Arterial-hepatic vein) concn.
difference (pmol/l)
Splanchnic uptake
(pmol/min)
Pyruvate
Arterial concn. (pmol/l)
(Arterial-hepatic vein) concn.
difference (pmol/l)
Splanchnic uptake
(pmol/min)
Lactate
Arterial concn. (pmol/l)
(Arterial-hepatic vein) concn.
difference (pmol/l)
Splanchnic uptake
(pmol/min)
Basal
( n= 10)
40
( n= 10)
50
(n=lO)
60
(n=9)
70
( n=6)
80
(n=5)
64f9
47 f 7
61f10
45f6
54f4
39f7
40 f 5*
26 f 8*
37 f 6**
25f5*
28 f 7**
17f6**
57fll
67f22
57f12
41 f 9
46f13
47f19
53f6
6f 5
52f5
7f4
52f4
14f2
49f4
14f 1
50f4
6f3
49f5
7f2
6f7
11 f 6
22f6
27f9
14f6
16f5
434 f 36
126 f 12
431 f 26
148fll
406 f 20
159f18
392 f 28
138f 16
386 f 25
112f17
387 f 30
75fll*
147 f 25
192 f 27.
217 37*
*
243 45*
*
188f34
167f33
4.29 f 0.1 1
- 0.60 f 0.43
4.26 f 0.27
- 0.43 f 0.36
4.36 f 0.27
- 0.23 f 0.09
4.09 f 0.22
-0.63 f0.13
4.20 f 0.25
-0.16 f 0.16
- 0.6 1 f 0.50
- 0.40 f 0.43
-0.28f0.11
-0.89 f 0.23
-0.13 f 0.18
Glucose
4.36 f 0.26
Arterial concn. (mmol/l)
(Arterial-hepatic vein) concn. - 0.12 f 0.15
difference (mmol/l)
-0.18 f0.18
Splanchnic uptake
(mmol/min)
Adrenaline
Arterial concn. (nmol/l)
0.53 f0.12
0.45 f0.09
0.59f0.14
0.75 f0.18*
0.72 f0.18*
0.76 f0.18*
Noradrenaline
Arterial concn. (nmol/l)
0.90 f 0.15
0.82 f 0.09
0.98 f 0.08
1.32f0.16*
1.32 f 0.14**
1.46 f0.18**
Haemodynamic effects of intravenous adenosine
lipolysis [46]. In t h e present subjects, the arterial glycerol
concentration decreased by more than 50% without any
concomitant increase in the hepatic uptake of glycerol,
suggesting reduced lipolysis. This reduction was not
mediated by an adenosine-induced depression of sympathetic activity, which was, on the contrary, slightly
elevated. The results therefore suggest that exogenous
adenosine causes an inhibition of lipolysis but a maintained blood flow in adipose tissue. Whether the
inhibition of lipolysis is a local direct effect or also
involves interactions with regulatory hormones still
remains to be elucidated. This inhibition of the lipolytic
rate may be a factor that counteracts a direct vasodilatory
effect of exogenous adenosine in adipose tissue, since
enhanced lipolysis is known t o be associated with an
augmented blood flow [46].
Conclusion
It is concluded that exogenous adenosine produced a
dose-dependent reduction in systemic vascular resistance,
accompanied by increased cardiac output, thereby maintaining mean arterial blood pressure in healthy conscious
volunteers. The vasculatures in the skin and splanchnic
regions may be more sensitive t o adenosine than those of
skeletal muscle and adipose tissue. A marked antilipolytic effect of exogenous adenosine was also demonstrated.
ACKNOWLEDGMENTS
This study was supported by grants from t h e Swedish
Medical Society, the Swedish Medical Research Council
(project nos. 7154 and 7485) and the Karolinska Institute.
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