1. No category

Muscle blood flow during forearm exercise in patients with severe heart failure.
J M Arnold, J P Ribeiro and W S Colucci
Circulation. 1990;82:465-472
doi: 10.1161/01.CIR.82.2.465
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1990 American Heart Association, Inc. All rights reserved.
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465
Muscle Blood Flow During Forearm Exercise
in Patients With Severe Heart Failure
J. Malcolm
0.
Arnold, MD, Jorge P. Ribeiro, MD, DSc, and Wilson S. Colucci, MD
Muscle fatigue is a prominent symptom in patients with chronic heart failure (CHF). To
determine whether it results from an intrinsic abnormality of vasodilating capacity of the
vasculature in exercising muscle, we studied local forearm blood flow (FBF) during exercise in
13 patients with severe CHF and in eight normal untrained subjects of similar age. Intermittent
forearm static exercise was performed by squeezing a hand dynamometer for 5 seconds, three
times per minute, for 5 minutes at 15%, 30%, and 45% of maximum voluntary contraction. FBF
was measured by mercury-in-rubber strain gauge venous plethysmography at baseline before
exercise and during the last 3 minutes of each exercise stage. Exercise was repeated after 24
hours of intravenous administration of milrinone in the patients with CHF. FBF increased with
forearm exercise in a reproducible manner during 24 hours in the normal subjects: rest,
2.54±0.23 (0 hours), 2.90±0.23, (24 hours); 15%, 7.25±0.92, 5.85±0.56; 30%17, 9.20±1.08,
10.05±0.85; 45%, 14.62±1.64, 13.85± 1.09 ml/100 mllmin;p=NS, 0 versus 24 hours. In patients
with CHF, FBF was reduced at baseline compared with normal subjects (1.70±0.15 ml/100
ml/min, p<0.05), but no significant differences from normal subjects were observed during
exercise (15%, 5.04+0.65; 30%, 7.64±0.99; 45%, 12.56+1.20 ml/100 mlmin). Peak exercise
blood flow was correlated negatively with central venous pressure (r=-0.65, p<0.05) and
positively with right ventricular ejection fraction (r=0.59, p<0.05). Twenty-four hours of
intravenous milrinone administration did not significantly alter FBF during exercise. Similar
results were seen for forearm vascular resistance and percent forearm oxygen extraction. The
exercise protocol did not significantly increase cardiac output in CHF patients (n=4) (baseline,
3.93±0.77; 45%, 4.05±0.63 1/min; p=NS). Because FBF was not significantly reduced during
submaximal forearm exercise in patients with severe CHF or improved by milrinone therapy,
we conclude that 1) a reduction in vasodilator capacity is not limiting at submaximal work
loads, and 2) an improvement in submaximal functional performance with milrinone may not
be secondary to increased intrinsic vasodilation of muscle vasculature during exercise.
Alternative explanations for muscle fatigue during whole-body exercise may include inadequate
cardiac output response or abnormalities in muscle metabolism. (Circulation 1990;82:465-472)
In patients with chronic heart failure (CHF),
exercise capacity is usually limited by symptoms
of dyspnea or fatigue. If the exercise is gradual
rather than abrupt in its onset and severity, fatigue is
more likely to result.' The specific cause of fatigue
remains unclear, but decreases in nutritive blood
flow,2,3 changes in muscle metabolism,45 and histological muscle fiber atrophy6 have been implicated.
From the University of Western Ontario (J.M.O.A.), London,
Ontario, and the Cardiovascular Division (J.P.R., W.S.C.),
Department of Medicine, Brigham and Women's Hospital and
Harvard Medical School, Boston, Massachusetts.
Supported in part by the Heart and Stroke Foundation of
Ontario, grant AN 1006. J.M.O.A. is a PMAC Career Health
Scientist.
Address for correspondence: J. Malcolm 0. Arnold, MD, FRCP
Edin, FRCPC, FACP, Cardiology Division, Victoria Hospital, 375
South Street, London, Ontario N6A 4G5, Canada.
Received October 11, 1988; revision accepted March 20, 1990.
Peripheral blood flow is reduced at rest in patients
with CHF.78 During upright exercise, blood flow to an
exercising limb remains reduced,2 but this could be
due to either a reduction in cardiac output and arterial
pressure or increased vascular tone. By studying forearm blood flow (FBF) during forearm exercise in
patients with CHF, it should be possible to differentiate these two contributions. However, Zelis et a19 in
a group of patients with severe rheumatic heart disease and fluid retention (New York Heart Association
[NYHA] functional classes III and IV) found an
inadequate arteriolar dilation during forearm exercise, whereas Wilson et al'0 suggested that vasodilation was not intrinsically impaired in patients with
nonedematous CHF (NYHA classes II and III).
Our present study was designed to address two
issues: 1) Is blood flow to a single exercising forearm
limb reduced in patients with severe CHF? 2) Does
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466
Circulation Vol 82, No 2, August 1990
TABLE 1. Characteristics of Study Patients With Chronic Heart Failure
Duration of
Evidence of
NYHA
LVEF
RVEF
symptoms
peripheral
Patient
class
(yr)
(%)
(%)
edema
(mo)
1
65
IV
7
25
60
None
2
43
IV
24
13
39
+ + +/4
3
IV
72
16
18
36
+ +/2
4
51
IV
15
NA
60
None
5
43
III
17
47
9
None
64
6
III
21
65
68
+14
7
32
IV
16
9
43
None
56
8
6
14
26
IV
+/4
9
40
III
13
39
15
+/4
44
16
34
21
10
III
None
8
11
69
55
11
IV
+/4
9
70
15
12
IV
24
++/
10
53
35
15
13
IV
None
CHF, chronic heart failure; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; RVEF,
right ventricular ejection fraction; CAD, coronary artery disease; DCM, dilated cardiomyopathy; NA, could not be
Age
Etiology
of CHF
CAD
DCM
CAD
DCM
CAD
CAD
DCM
DCM
DCM
CAD
CAD
DCM
CAD
analyzed.
milrinone, a new positive inotropic vasodilator that
improves functional exercise capacity acutely,11,12
improve blood flow during exercise because of
peripheral vasodilation?
Methods
Study Population
We studied 13 patients with CHF (11 men and two
women) who had a mean age of 54±4 years (range,
32 to 72 years) (Table 1). The etiology of CHF was
coronary artery disease in seven and idiopathic
dilated cardiomyopathy in six. All had severe left
ventricular dysfunction with a mean left ventricular
ejection fraction of 13.7±1.5% (range 6 to 24%) by
radionuclide gated blood pool estimates. All patients
had a documented clinical history of CHF (NYHA
functional class III [n=4] or IV [n=9]), were receiving digoxin and diuretics, and had been clinically
stable for at least 2 weeks. At the time of study, none
had decompensated left ventricular failure.
Eight normal subjects (seven men and one woman)
of similar age (mean, 49±3 years; range, 38 to 66
years) served as our control group. All were untrained, drug-free subjects with a sedentary lifestyle
and had no evidence of heart disease by clinical
history, physical examination, electrocardiography,
or chest radiography.
The protocol was approved by the Human Subjects
Review Committee of the institutions, and written,
informed consent was obtained.
Protocol
CHF patients had been on a 2-g sodium diet and a
stable dose of medications for at least 3 days before
enrollment. All vasodilators were then withheld for
at least 48 hours before study, and digoxin and
diuretics were withheld on the morning of the study.
A flow-directed triple lumen thermodilution catheter
was inserted into the pulmonary artery through the
right internal jugular vein on the first morning of the
study in the CHF patients only. An intravenous
catheter was inserted into an antecubital vein in the
dominant arm of all subjects, and the tip was
advanced 6 in. proximally to sample mixed venous
blood draining the forearm. Maximum voluntary
contraction of the dominant forearm was measured
with a hand dynamometer (Jamar, Alimed, Boston,
Mass.). Arterial pressure was measured in the opposite arm through an intra-arterial line in the CHF
patients and with a semiautomated indirect recorder
(Dinamap 845XT, Critikon, Tampa, Fla.) in the
normal subjects.
All studies were performed in a quiet, temperature-controlled environment (22-24° C) after an
overnight fast. Patients and normal subjects were
recumbent with head and shoulders comfortably supported. After 30 minutes of rest, baseline measurements of heart rate, blood pressure, cardiac output,
pulmonary capillary wedge pressure, and FBF were
obtained. FBF was measured with a mercuryin-Silastic rubber strain gauge applied around the
dominant forearm, which was comfortably supported
above the level of the heart.13 A wrist cuff was
inflated to 200 mm Hg 1 minute before recordings to
exclude hand blood flow.14 A venous occlusion pressure of 40 mm Hg was used in the upper arm cuff,
and FBF was measured as the slope of the change in
forearm volume. The venous cuff was inflated for
5-10 seconds for each flow measurement, then
released. The mean of at least six flows was obtained
at each measurement time. The mean of two sets of
baseline flows was used as the control flow.
After a stable hemodynamic baseline had been
obtained, forearm exercise was commenced and consisted of repetitive contractions on the hand dynamometer maintained for 5 seconds and released for
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Amold et al Muscle Blood Flow During Forearm Exercise
15 seconds, similar to that described by Zelis et al.9
Exercise was performed for 5 minutes at 15%, 30%,
and 45% of maximum voluntary contraction. All
patients and normal subjects were able to complete
the full protocol, but some required encouragement
because of fatigue. No patients complained of painful
muscles, although some normal subjects complained
of discomfort in the hand during the last minute of
exercise after inflation of the wrist cuff. Hemodynamics and FBF were measured during the last 3 minutes
of each exercise stage, and FBF was measured during
relaxation between contractions as described and
validated by Longhurst et al.15 Oxygen saturation of
mixed venous blood (Hemoximeter OSM2, Radiometer, Copenhagen) draining the exercising forearm
was measured before and at the end of each exercise
stage (immediately after the last flow measurement,
during muscle relaxation). Arterial oxygen saturation
was measured from the intra-arterial line in CHF
patients and from a warmed earlobe capillary sample
in the normal subjects. In five CHF patients, arterial
samples were taken before exercise and at the end of
each stage of exercise, but no significant change in
oxygen saturation was observed with this forearm
exercise protocol (rest, 95.5±0.9%; 15%, 94.7±1.2%;
30%, 94.1±1.3%; 45%, 95.0±0.7%). Therefore, in
subsequent patients and normal subjects, arterial
oxygen saturation was measured before exercise only.
Normal subjects were restudied in an identical
fashion 24 hours later. Intravenous and arterial lines
were left in situ in the CHF patients who received a
48-hour intravenous infusion of milrinone (50 gg/kg
during 10 minutes, 0.25 or 0.5 ,gg/kg/min for 6 hours,
0.5 ,ug/kg/min to 48 hours) during which repeat
forearm exercise testing was performed at 24 hours.
Plasma milrinone concentration between 24 and 48
hours of infusion was 166±18 ng/ml. The full hemodynamic effects of a 48-hour infusion of milrinone in
these patients are reported elsewhere with the results
of a multicenter trial.16
Neurohormones were assayed at rest in eight
CHF patients. Plasma norepinephrine concentration was measured by a standard radioenzymatic
technique17 and was 472±76 pg/ml. Plasma renin
activity was measured by radioimmunoassayl8 and
was 11.0±3.0 ng/ml/hr.
Measured Variables
Mean blood pressure was calculated as diastolic plus
one third pulse pressure in the normal subjects and as
the integrated intra-arterial pressure in patients with
CHF. Forearm vascular resistance was calculated as
mean blood pressure divided by FBF and is expressed
in arbitrary units. Blood oxygen content was calculated
as the product of hemoglobin concentration, 1.36 ml
OJg of hemoglobin, and percent oxygen saturation.
Oxygen extraction was calculated as the percent ratio of
the arteriovenous oxygen difference and arterial oxygen
content, and oxygen consumption (ml 01minm 100 ml)
as the product of the arteriovenous oxygen difference
and FBF divided by 100. Cardiac output was calculated
16
467
-
14
-
12
-
(/~~~~~~~
E 6-
8
4-
O
L - ,-
/
2-
ReSt
15%
30%
EXerCiSe
4596
FIGURE 1. Plot of forearmn blood flow (FBF) at rest and
duting foreanm exercise in nonnal subjects stucdied on 2
consecutive days o, Day 1; *, day 2. p=NS day 1 vs. day 2.
*p<.Ol FBF vs. preceding FBF on day 1.
by thermodilution from the mean of at least three
injections differing by less than 10%, and cardiac index
was calculated as (I/min/M2). Pulmonary capillary
wedge pressure was measured at end expiration. Systemic vascular resistance (dyne-*sec/cm5) was calculated as 80 multiplied by (mean blood pressure minus
right atrial pressure) divided by cardiac output.
Statistical Analysis
Increases in FBF during exercise in normal subjects
were compared by analysis of variance for repeated
measures with contrasts performed with Tukey's
method.19 Hemodynamic data at 0 and 24 hours were
compared with paired t tests. A p value less than 0.05
was considered significant. Data from CHF patients
before milrinone therapy were compared by unpaired
t tests with normal subjects at day 1 and CHF patients
after milrinone therapy at each level of exercise and
p< 0.025 was considered significant. Linear regression
was performed with the least-squares method. All
values are expressed as mean-+SEM.
Results
To assess the reproducibility of the exercise protocol. the results from the normal subjects on the two
consecutive days are shown in Figure 1. With each
stage of exercise, there was a progressive increase in
FBF, but no significant differences were seen
between the FBFs of the two days at any level of
exercise, confirming good reproducibility. Therefore,
for clarity, the subsequent figures show only the
normal results from day 1.
To confirm that the forearm exercise protocol was
p-rodcll-ingr local vascuilalr cagswithouit a change(
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2014
iin
Circulation Vol 82, No 2, August 1990
468
A
B
16o Normals
A CHF Pre MIL
& CHF Post MIL
1412-
FIGURE 2. Panel A: Forearm blood
60-
flow (FBF) at rest and during forearm
c
._
m c) 8-
40cr 0
E1 6-
>c 30-
4-
20-
21
10-
(I
nu a
1
C
1.4-
60c
x
W
E 1.0-
E 0.8-
g 40-
C._
.
D
1.2-
500
exercise in patients with chronic heart
failure (CHF) studied before and after
24 hours of intravenous administration
ofmilrinone (MIL). Panel B: Forearm
vascular resistance (FVR) at rest and
during forearm exercise in CHF
patients studied before and after 24
hours of intravenous MIL. Panel C:
Percent forearm oxygen extraction at
rest and during forearm exercise in
CHF patients studied before and after
24 hours of intravenous MIL. Panel D:
Forearm oxygen consumption at rest
and during forearm exercise in CHF
patients studied before and after 24
hours of intravenous MIL. o, Normal
subjects (day 1); A, pre-MIL; A, postMIL. *p<0.01, **p<0.001 vs. preMIL. Exercise is expressed as percentage of maximum voluntary contraction.
50-
E10-
m
'
cEO 6-i
30-
( CV
20-
(M
10v
(l
0
oE
0.4-
0.2,.
Rest
U
1
15%
30%
Exercise
45%
.
1
Rest
central pump function, hemodynamics were measured
before and at peak forearm exercise before milrinone
therapy in 12 CHF patients. Forearm exercise in CHF
patients resulted in no significant changes in heart rate
(89±3 and 90±3 beats/min), mean blood pressure
(75 ±3 and 77±3 mm Hg), pulmonary artery diastolic
pressure (27±3 and 28±2 mm Hg), right atrial pressure (10±2 and 10±2 mm Hg), or cardiac output
(3.93±0.77 and 4.05±0.63 1/min, n=4). In normal
subjects, the protocol did not increase heart rate
(65 ±4 and 69±4 beats/min), and mean blood pressure
tended to increase slightly (rest, 94±4; 15%, 97+4;
30%, 102±3; 45%, 107±3 mm Hg;p=0.06).
FBF responses to forearm exercise in the CHF
patients are shown in Figure 2A. Before milrinone
therapy, FBF was reduced at rest in the CHF patients
compared with the normal subjects (p<0.05); however, FBF progressively increased with exercise and
was not significantly different from that in normal
subjects. After milrinone therapy, FBF was significantly increased at rest, but exercise blood flow was
not altered. Similar changes were seen with forearm
vascular resistance (Figure 2B) and percent forearm
oxygen extraction (Figure 2C), which were both
increased at rest in patients with CHF. Milrinone
therapy decreased forearm vascular resistance and
percent oxygen extraction at rest but did not alter
either variable from that seen in normal subjects at
each stage of exercise. Indeed, because forearm
vascular resistance was higher at rest in patients with
l
15%
30%
Exercise
45I%
CHF than in normal subjects, yet the same at peak
exercise, the reduction in forearm vascular resistance
achieved during forearm exercise by patients with
CHF (41.1+4.0 units) tended to be greater than that
in normal subjects (31.4±3.5 units), although it did
not reach statistical significance. Forearm oxygen
consumption (Figure 2D) was normal in CHF
patients at rest and was not altered by milrinone at
rest or during exercise.
Because the control group completed more physical work than the CHF group, the results are also
shown in Figure 3 as the force developed with each
contraction. This illustrates that the points for the
control group have moved to the right and that
differences from the CHF group are further reduced
for FBF, forearm vascular resistance, and oxygen
consumption. Percent forearm oxygen extraction
remains increased in the CHF group to maintain
normal oxygen consumption because hemoglobin was
lower in the CHF patients (12.4 +0.5 versus 14.3+0.4
g%, p<O.Ol).
FBF during exercise at 45% of maximum voluntary contraction was found to correlate negatively
with resting central venous pressure and positively
with resting right ventricular ejection fraction (Figure 4). No correlation was seen between exercise
blood flow and resting plasma norepinephrine levels or plasma renin activity.
At rest, milrinone significantly improved cardiac
index (2.92±0.28 at 24 hours versus 2.12±0.25
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2014
Amold et al Muscle Blood Flow During Forearm Exercise
A
469
B
6050-
1.2
-
40-
*E
>.
30-
LL M
4-
20-
2-
10-
0-
U .*
C
l
l
l
A
D
60-
50-
o 40x
3020h10nv-.-
l
10
l
20
l
30
l
40
40
30
20
Kg
Kg
FIGURE 3. Panel A: Forearm blood flow (FBF) at rest and during forearm exercise in patients with chronic heart failure (CHF)
studied before and after 24 hours of intravenous administration of milrinone (MIL). Panel B: Forearm vascular resistance (FVR)
at rest and duringforearm exercise in CHFpatients studied before and after 24 hours of intravenous MIL. Panel C: Percent forearm
oxygen extraction at rest and during forearm exercise in CHF patients studied before and after 24 hours of intravenous MIL. Panel
D: Forearm oxygen consumption at rest and during forearm exercise in CHF patients studied before and after 24 hours of
intravenous MIL. o, Normal subjects (day 1); A, pre-MIL; A, post-MIL. *p<0.01, * *p<0. 001 vs. pre-MIL. Exercise is expressed
as force developed (kg) with each contraction.
Rest
1/min/m2 preinfusion, p<0.005) with a reduction in
systemic vascular resistance (1,061 + 110 at 24 hours
versus 1,382±143 preinfusion, p<0.01). Milrinone
therapy tended to reduce pulmonary capillary
wedge pressure (20.4± 1.4 versus 23.7± 1.8 mm Hg)
and right atrial pressure (7.0±+1.3 versus 8.4±1.9
mm Hg), with small increases in mean blood pressure (72.1±2.5 versus 70.9±3.9 mm Hg) and heart
rate (90.2±3.4 versus 86.1±3.0 beats/min), but
these changes were not significant.
Discussion
Using a reproducible protocol of forearm exercise
that did not cause significant central hemodynamic
changes in patients with severe CHF, we showed no
difference between CHF patients and normal subjects of similar age in the ability of their forearm
vasculature to dilate and increase blood flow during
exercise. This occurred even though their exercise
functional capacity by clinical assessment was significantly reduced and suggests that the development of
fatigue during exercise may not primarily result from
an intrinsic defect in the vasodilating capacity of the
muscle vasculature. This conclusion is supported by
the observation that milrinone, a drug known to
improve exercise capacity acutely in patients with
CHF, although producing vasodilation at rest, did not
improve vasodilation during forearm exercise.
The protocol used in this study required exercise to
45% of maximum voluntary contraction for 5 minutes, and the end point was not chosen to be maximum symptom-limited exercise capacity. However,
all patients and normal subjects complained of
fatigue during the protocol, and submaximal exercise
may be more relevant to a patient's performance of
activities of daily living than maximal exercise. The
protocol was designed to be similar to that described
by Zelis et al,9 except that we adjusted the strength of
contraction to allow for different muscle mass in
individual patients. If the present results are considered as force developed, then the patients with CHF
generated less force but had a similar vasodilation to
normal subjects, further supporting the conclusion
that the ability of their forearm muscle vasculature to
dilate was not impaired.
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470
Circulation Vol 82, No 2, August 1990
24-
r= -0.65
p<0.05
20-
Qc
0
>'g16-
i
8-
UIDO 12-
0
0
0Z
El~~~~~~
0
8~~~~~~~~~~~~~~~~~~~~1
IL-
4a
l
X
4
8
12
16
24
20
CVP mmHg
24-
20f
_E 16ae E
g 12L
L
?-
E 8r
=
p<
4-
0.59
0.05
ut
e
0
20
40
RVEF %
60
FIGURE 4. Plots of correlation ofpeak forearm blood flow
(FBF) during forearm exercise at 45% of maximum voluntary
contraction (MVC) with central venous pressure (CVP) and
right ventricular ejection fraction (RVEF) in patients with
chronic heart failure.
This type of forearm exercise increased local muscle blood flow but did not increase cardiac output in
the CHF patients. This represents an approximate 10
ml/min increase in FBF per 100 ml forearm volume.
If the average forearm volume is 1,000 ml, then
cardiac output would have been expected to increase
100 ml/min or 0.1 1/min. This is less than the measurement error of the thermodilution technique, and
therefore, we cannot confirm whether the local
increase in FBF resulted from a true central increase
or merely a redistribution of cardiac output.
Despite similar protocols, our conclusions differ
from those of Zelis et a19 and may reflect the subset
of patients they studied, all of whom had rheumatic
heart disease and clinical evidence of right ventricular decompensation with fluid retention. Diuresis
alone in these circumstances improves vasodilator
reserve capacity.20 We did find a correlation between
peak exercise blood flow and right ventricular dysfunction, as reflected by central venous pressure and
right ventricular ejection fraction. This is of interest
because right atrial pressure is known to negatively
correlate with survival,2' and right ventricular rather
than left ventricular ejection fraction correlates with
upright exercise capacity in CHF.22 Although
increased central venous pressure could be associated with increased tissue sodium and water retention and a decrease in vasodilator capacity, in an
experimental animal model of heart failure induced
by rapid atrial pacing, modest increases in mean right
atrial pressure with evidence of some fluid retention
and increased muscle water content were not associated with a decrease in peripheral arterial vasodilation.23 The degree of fluid retention was variable
among the animals, and the investigators did not
report a correlation between degree of fluid retention or central venous pressure and vasodilator
capacity. Thus, it remains possible that the decrease
in exercise blood flow seen by Zelis et a19 reflected
local tissue edema secondary to the very high venous
pressures present in their patients.24,25
Severe heart failure is also associated with neurohormonal activation,26,27 and plasma norepinephrine
has been shown to correlate positively with right
atrial pressure.28 This neurohormonal activation
could be a further independent influence on vasodilator capacity, although we found no association with
plasma norepinephrine levels or plasma renin activity
in our patients. Another consideration is that venous
plethysmography assumes the veins are empty at rest.
With high right atrial pressures, this may not be so,
and thus, further small increments in forearm volume
during intermittent venous occlusion may be operating on a flattened portion of the venous pressurevolume curve,29 thus underestimating forearm blood
flow. However, significant flattening of the curve does
not occur until pressures higher than 20 mm Hg, and
this elevation of right atrial pressure was present in
only one of our patients.
Our results support the observations of Wilson et
al,10 who studied a group of nonedematous patients
with less severe clinical heart failure (NYHA classes
II and III) than our population, but they used a
different protocol of forearm exercise. Blood flow
responses in the forearm30 and biochemical alterations within the muscle31 can be dependent on the
exercise protocol used. However, Wilson et al10 also
found increases in blood flow to be similar between
normal subjects and patients, suggesting that the
reduced vasodilation seen by Zelis et a19 is more
likely to be due to the edematous condition of the
patients they studied rather than to differences in
exercise protocol. In addition, our observations on
the effects of milrinone further support the conclusion that improvements in exercise capacity of
patients with compensated severe heart failure may
not be mediated through alterations in the intrinsic
vasodilator capacity of muscle blood vessels. Our
results differ from those of LeJemtel et al,3 who
compared one-leg with two-leg maximal bicycle exercise and concluded that the ability of the muscle
vasculature to vasodilate is impaired in patients with
CHF. However, oxygen uptake was significantly
increased in their model, and thus, changes in cardiac
output could have influenced their measurements of
blood flow. Sullivan et a132 also studied leg blood flow
Downloaded from http://circ.ahajournals.org/ by guest on September 11, 2014
Amold et al Muscle Blood Flow During Forearm Exercise
during maximal upright bicycle exercise and found
evidence of reduced perfusion at rest and during
exercise. Because nonleg blood flow and arterial
pressure were preferentially maintained during exercise at the expense of leg hypoperfusion, they concluded that a reflex-mediated peripheral vasoconstriction may occur in the exercising limb in the
setting of an inadequate cardiac output response.
Our findings complement the results of this study,
because we studied a small muscle mass, without a
change in cardiac output, and found no intrinsic
abnormality in vasodilator capacity with exercise.
Improved functional capacity after vasodilator
therapy in CHF could occur through other mechanisms such as increased cardiac output. During
whole-body upright exercise, this could maintain
muscle perfusion and perhaps performance. Thus,
our results are not inconsistent with previous observations during upright exercise that blood flow to
exercising skeletal muscle is reduced in CHF2 and
improved by long-term administration of drugs such
as captopril that increase maximum oxygen uptake.33
Muscle fatigue and decreased performance may also
involve alterations in skeletal muscle metabolism
with increased phosphocreatine depletion and low
pH.455Two studies in patients with heart failure have
suggested that these changes do not appear to be
secondary to impaired blood flow or muscle atrophy.34'35 Also, of interest, in a rat model of myocardial infarction and acute heart failure, milrinone
preferentially increased blood flow to oxidative
rather than glycolytic working muscle during maximal
treadmill exercise.36 Hence, although total FBF was
not increased in our patients, milrinone may improve
the distribution between oxidative and glycolytic
muscle fibers. If oxidative muscle fibers were to have
better resistance to fatigue compared with glycolytic
fibers, then this would be clinically helpful.
In summary, we found no impairment in the ability
of the local vasculature to dilate during submaximal,
intermittent forearm static exercise in patients with
compensated severe CHF despite the presence of
mild-to-moderate peripheral edema in some patients.
Milrinone did not further increase exercise forearm
blood flow. We conclude that impairment of functional exercise capacity in patients with CHF is
unlikely to be due primarily to an intrinsic vasodilator
abnormality of muscle blood vessels.
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Acknowledgments
We acknowledge the expert help of Diane Gauthier, BSc, RN, Gail Burton, RN, Gordon Marchiori,
PhD, and the excellent secretarial assistance of Paula
Hugin and Dale Arts.
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KEY WORDS * heart failure * exercise, forearm * blood flow,
muscle * milrinone
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