(Circulation. 1996;93:953-959.)
© 1996 American Heart Association, Inc.
Articles |
Failure of Reflex Venoconstriction During Exercise in Patients With Vasovagal Syncope
From the Heart Failure Research Unit, Department of Medicine, University of Queensland, Royal Brisbane (Queensland, Australia) Hospital.
Correspondence to Prof Michael Frenneaux, Cardiology Department, Royal Brisbane Hospital, Herston Rd, Brisbane, Australia 4029.
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Abstract |
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Background In this study, we tested two hypotheses. First, we tested the hypothesis that reflex constriction of the venous capacitance beds in patients with vasovagal syncope is impaired during both subhypotensive lower-body negative pressure. Second, we proposed that splenic venoconstriction may be impaired during exercise in patients with vasovagal syncope.
Methods and Results We evaluated 25 patients with vasovagal syncope (age, 45.0±15.9 years; 12 men, 13 women) and 24 control subjects (age, 41.3±13.7 years; 16 men, 8 women). A nuclear technique was used to assess changes in forearm venous tone during lower-body negative pressure and in splenic venous volume during cycle exercise. Changes in forearm vascular resistance (FVR) during cycle exercise were assessed with a strain-gauge plethysmography technique. The percentage reduction in unstressed forearm vascular volume during lower-body negative pressure was similar in patients and control subjects (9.0±8.0% versus 9.7±5.9%, P=NS). During exercise, splenic venous volume decreased less in patients than in control subjects (15.8±21.7% versus 42.6±12.6%, P<.0001). FVR decreased by 2±32% in patients but increased 108±90% in control subjects (P<.0001). There was no relation between percentage change in splenic volume and percentage change in FVR during exercise in either patients or control subjects (r=-.06, P=NS and r=-.18, P=NS, respectively).
Conclusions Patients with vasovagal syncope exhibit a failure of the normal increase in tone in the splenic capacitance bed and in forearm resistance vessels during dynamic exercise. Forearm venous tone increases normally during lower-body negative pressure.
Key Words: syncope • baroreceptors
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Introduction |
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Vasovagal syncope is a common disorder. Common precipitants include prolonged standing, emotion, and pain. Activation of left ventricular mechanoreceptors,1 especially in the setting of an underfilled hypercontractile ventricle, has been proposed as a mechanism of the vasovagal response.2 Stimulation of these receptors leads to reflex bradycardia and hypotension.3 4 Sneddon et al5 demonstrated impaired immediate vasoconstrictor responses during head-up tilt in patients with recurrent neurally mediated syncope, long before the onset of overt vasovagal syncope, which suggests an abnormality in cardiopulmonary baroreceptor reflex arc. Recent animal6 and clinical7 evidence calls the central role of this mechanism into question, at least in some patients. It was proposed recently that activation of other cardiopulmonary mechanoreceptors in the atria or great veins may be responsible for vasovagal syncope.8 The observation of a greater reduction in left ventricular volumes and increases in ejection fraction during tilt table testing in patients with vasovagal syncope than in control subjects also has been considered support for the concept that the vasovagal response may be related to a sudden reduction in cardiac volume.9 10 11 This might be explained by a failure or overriding of normal reflex venoconstriction in response to postural stress. Alternatively, the exaggerated decrease in cardiac volume may be a consequence of the vasovagal reaction (caused by the greater decrease in systemic vascular resistance) rather than its cause.
We previously demonstrated that patients with vasovagal syncope exhibit impaired constriction or paradoxical vasodilation instead of the normal reflex vasoconstrictor response of resistance vessels in nonactive muscle during exercise.12 In another report, we suggested that exercise syncope in some patients with normal hearts may be a variant of vasovagal syncope.13 This raises the possibility that patients with vasovagal syncope may have an exaggerated reflex response from cardiopulmonary mechanoreceptors during exercise, overriding the normal baroreflex vasoconstrictor mechanisms and leading to vasodilation. Dynamic leg exercise in normal subjects is associated with both a marked reduction in splanchnic venous capacitance14 and vasoconstriction of resistance vessels in nonexercising muscle.15 The latter helps to maintain or augment stroke volume in the face of the reduced diastolic filling time that accompanies exercise sinus tachycardia, thereby compensating for the diversion of blood volume to exercising muscles.
We tested two hypotheses in this study. First, we proposed that forearm venoconstriction may be impaired during application of subhypotensive lower-body negative pressure (LBNP) in patients with vasovagal syncope (ie, at a level of LBNP insufficient to induce an overt vasovagal response). Impaired venoconstriction might lead to the small hypercontractile ventricle proposed as the mechanism of the vasovagal response. We assessed this by plotting the forearm volume-pressure relation before and during LBNP to characterize the venous response. This method allows assessment of changes in venous tone. If the volume-pressure coordinates fall on a different curve during LBNP, an intrinsic change in forearm venous properties is implied (active venous response), whereas movement along the same volume-pressure curve represents no change in these intrinsic venous properties (passive venous response). Second, we proposed that splenic venoconstriction may be impaired during exercise in patients with vasovagal syncope and that this is associated with the impaired reflex increase in tone in resistance vessels that we previously described in patients with vasovagal syncope.12 13
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Methods |
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Patients
Sixty-eight patients were referred to the Royal Brisbane (Australia) Hospital Syncope Clinic between January 1993 and November 1994 for assessment of syncope. A diagnosis of vasovagal syncope was established in 35 patients on the basis of a typical history, negative cardiovascular and neurological examinations, normal echocardiography, a negative EEG and cardiac electrophysiological study (where appropriate), and a positive head-up tilt test without isoproterenol (45 minutes at 60° tilt). Patients who were not in sinus rhythm were excluded. Of these 35 patients, 25 (12 men, 13 women; age, 20 to 70 years [mean age, 45.0 years]) satisfied the above entry criteria and consented to be included in the study. Twenty-four normal subjects (16 men, 8 women; age, 21 to 70 years [mean age, 41.3 years]) from the Gastroenterology Department endoscopy database with no previous cardiac history or current symptoms, normal cardiovascular examination, normal ECG and echocardiogram, and a negative tilt test were enrolled as control subjects.
Study Protocol
The investigations were performed at the Royal
Brisbane Hospital
with the approval of the hospital ethics committee. Informed consent
was obtained from all patients and control subjects. Each subject was
studied on 3 consecutive days at 8 AM after fasting since
midnight. No control subjects were on vasoactive medications. Of the
patients with vasovagal syncope, 3 had been taking vasoactive
medications before enrollment in the study (atenolol 50 mg daily in 1,
metoprolol 50 mg twice daily in 1, and sotalol 80 mg twice daily in 1).
All vasoactive medications were withdrawn for at least five
half-lives before the study. The radionuclide scintigraphic studies
were performed on day 1, and assessment of exercise forearm vascular
responses during dynamic leg exercise was done on day 2.
Red Cell Labeling
Red cells were labeled with
99mTc pertechnetate by a
modified in vivo technique. A cannula was inserted into an antecubital
vein of the left arm. Ten minutes after intravenous
injection of 
1.7 mg of stannous pyrophosphate, 5 mL blood was drawn
into a heparinized syringe and incubated for 20 minutes with 925 MBq
(25 mCi) of 99mTc pertechnetate before reinjection.
Assessment of Changes in Forearm Venous Tone During Application of
Subhypotensive LBNP
The subjects lay in a specially constructed LBNP
bed and were
allowed to rest for 20 minutes. The laboratory was quiet and maintained
at a constant temperature of 22°C to 24°C. Venous tone was assessed
in the forearm with a standard radionuclide volume-pressure
technique.16 In brief, a sphygmomanometer cuff was placed
around the upper arm. The forearm was comfortably positioned and
restrained on the face of a wide-field-of-view gamma camera
(Siemens Orbiter ZLC) interfaced to a dedicated computer system (Max
Delta, Siemens) and equipped with a low-energy
general-purpose parallel-hole collimator. The region of
interest extended from the elbow to the wrist. The static image of the
forearm was recorded at 0, 10, 20, and 30 mm Hg venous occluding
pressure, beginning at 0 mm Hg and increasing stepwise at 90-second
intervals. The counts in the region of interest were acquired in the
final 30 seconds of each interval. Repeated studies were performed
during application of 20 mm Hg LBNP (insufficient to induce systemic
hypotension).
The count rate in this region of interest obtained with no occluding pressure or LBNP was arbitrarily taken to represent 100% forearm blood volume. All subsequent readings were expressed as a percentage of this value. Measures of scintigraphic vascular volumes (in percent units) at occluding cuff pressures of 0, 10, 20, and 30 mm Hg were used to construct venous volume-pressure plots after correction for physical decay.
Changes in Splenic Blood Volume During Erect Cycle
Exercise
One hour later, the patient was seated on an erect cycle
ergometer in a quiet room maintained at a constant room temperature of
22°C to 24°C. Imaging of the spleen was acquired on a
small-field-of-view gamma camera (GE 300A, GE Medical
Systems) fitted with a low-energy, general-purpose,
parallel-hole collimator and interfaced to a dedicated
microcomputer (Max Delta, Siemens). The detector was adjusted for the
posterior view with best imaging of the spleen. A 3-minute resting
acquisition was performed. Before exercise, a 5-mL blood sample was
drawn for subsequent analysis of radioactive counts per 1 mL.
The subjects then began exercise at a 25-W workload, increasing by 25-W
increments every 4 minutes until the patient was limited by symptoms.
Splenic counts were acquired continuously in 30-second epochs,
systolic pressure was measured by palpation at rest at the
middle of each stage of exercise and at peak exercise, and the ECG was
recorded continuously. In the final minute of exercise, another
5-mL blood sample was drawn for subsequent analysis of
radioactive counts per 1 mL. Exercise was terminated because of patient
fatigue or breathlessness.
Assessment of Changes in Right Atrial Pressure During Erect
Cycle Exercise
To explore the possibility that an attenuated reduction
in
splenic counts may reflect a shift caused by increased pressure along
the same venous volume-pressure relation rather than a failure to
appropriately increase venous tone, we measured right atrial pressure
during maximal erect cycle exercise in 5 patients with vasovagal
syncope who exhibited abnormal splenic venous responses in the initial
test and in 5 healthy approximately age-matched controls. A central
venous long line was inserted through the right antecubital fossa.
Pressures were measured with a Baxter transducer referenced to
atmosphere at the midchest level and recorded with an Acq Knowledge
data acquisition system (Biopac Systems) and an Apple Macintosh IIci
microcomputer.
Exercise Forearm Vascular Responses
Subjects were studied in
a quiet environment at a constant room
temperature of 22°C to 24°C. Forearm blood flow was measured with a
standard mercury-in-Silastic strain-gauge plethysmography
technique (Hokanson).17 Patients were positioned semierect
(at 70° to the horizontal) on a cycle ergometer. The right forearm
was elevated to allow free venous drainage. A pneumatic collecting cuff
was placed around the upper arm; a second cuff was placed around the
wrist and inflated for the duration of the recordings to
suprasystolic pressure to exclude hand circulation from the
measurements. Measurements of forearm blood flow were obtained by
inflating the collecting cuff to 40 mm Hg to prevent venous return.
Thus, the rate of increase of forearm girth was proportional to forearm
blood flow. The cuff was inflated for 10 seconds and then deflated for
10 seconds. This was repeated three times, and the forearm flow was
calculated from the mean of the three slopes. The volume variations of
the limb segment were measured by means of the electrical resistance
variations of the mercury-filled strain gauge. The volume output
from the strain gauge was measured with a high-gain preamplifier
and recorded with surface ECG data by an Apple Macintosh IIci
computer and an Acq Knowledge multichannel data acquisition system.
Blood pressure was measured in the opposite limb with a mercury
sphygmomanometer. After measurements were made with patients at rest,
patients performed symptom-limited semierect cycle exercise,
beginning at 25 W and increasing by 25 W every 3 minutes. Forearm blood
flow was measured during the final minute of each stage of exercise.
Forearm vascular resistance (FVR), expressed in resistance units, was
calculated as the quotient of the mean arterial pressure
(in millimeters of mercury) and forearm blood flow (milliliter per
minute per 100 mL).
Data Analysis
Forearm Venous Tone During LBNP
At 0 and -20 mm Hg LBNP, forearm counts were assessed at
each venous occlusion pressure to give paired venous
volume-pressure plots for each patient. Linear regressions were
performed on each set of data points to determine whether a linear
model described the data. A linear model was accepted if
r>.8. We then determined whether the slopes of the two
lines in each data set were different (ie, to determine whether the
lines were parallel or not) using an established method for testing the
difference between two independent regressions.18
Unstressed venous volume was defined as the intercept on the volume axis. Changes in unstressed volume reflect changes in venous tone.
Splenic Counts During Erect Cycle Exercise
A region
of interest was drawn around the spleen, and counts
were measured within this region of interest. Resting and peak exercise
crude counts were corrected for the counts per gram in the blood
samples taken at rest and at peak exercise to assess changes in splenic
volume.
Statistics
Data are expressed as mean±SD. Statistical
analysis was
performed with paired and unpaired t tests, the
2 test, and linear regression as appropriate. A
value of P<.05 was considered significant.
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Results |
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Patient Characteristics
Of the patients, 12 were men and 13 were women 20 to 70 years of age (mean, 45.0 years). The control group consisted of 16 men and 8 women 21 to 70 years of age (mean, 41.3 years) (statistically similar in age to the patient group). On specific inquiry, 5 patients but no control subjects recalled a history of exercise syncope or presyncope. Of these patients, 3 had previously demonstrated exercise-induced hypotension during erect treadmill exercise according to standard criteria.19 The patients had suffered 9.4±8.1 episodes of syncope in the past, whereas no control subjects had any previous episodes of syncope.
Forearm Venous Responses During LBNP
Two volume-pressure
plots were performed for each subject, one
with the patient resting and one with -20 mm Hg LBNP applied.
Linear regressions were performed on each plot, and r values
were .87 to .99 (mean, .96±.03). Therefore, a linear model was
adopted. All control subjects and 24 of the 25 patients showed a
downward shift in the forearm volume-pressure relation during LBNP.
One patient showed a paradoxical upward shift in the
volume-pressure relation during LBNP (ie, her unstressed forearm
vascular volume increased by 15% during -20 mm Hg LBNP).
Although volume-pressure plots varied in slope (compliance) between
individuals, within individuals there was little change in slope
between control and LBNP states. Thus, shifts induced by LBNP were
parallel. To confirm this, we used a standard method18 to
test whether the slopes of each set of paired data were different and
found that they were not (P=NS).
All patients and
control subjects completed the LBNP study without
complications. As Table 1
shows, heart rate and
systolic pressure in the two groups were similar at rest and at
-20 mm Hg LBNP. In no subject was systolic pressure
during LBNP >10 mm Hg lower than at rest.
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The percentage change in
forearm counts at -20 mm Hg
compared with rest was similar in patients and control subjects. Linear
regression yielded the equations V=Detected Activity
(cps)=647+5.90xBefore and V=Detected Activity
(cps)=593+5.90xDuring -20 mm Hg LBNP in patients with
vasovagal syncope (P<.0001). In normal subjects, linear
regression yielded the equations V=Detected Activity
(cps)=609+5.90xBefore and V=Detected Activity
(cps)=543+5.90xDuring -20 mm Hg LBNP
(P<.0001).
The percentage decrease in unstressed forearm vascular volume during
application of LBNP was similar in patients and control subjects
(9.0±8.0% versus 9.7±5.9%, P=NS). Fig
1
is an example of volume-pressure plots both at rest and during
-20 mm Hg LBNP from 1 patient.
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Splenic Volumes During Erect Cycle Exercise Testing
The erect
cycle exercise test was completed without complication
in all patients and control subjects. As Table 2 shows,
heart rate and systolic pressure were similar at rest in
patients and control subjects. At peak exercise, heart rate was similar
in the two groups, whereas systolic pressure was markedly lower
in patients versus control subjects (165±23 versus 191±12 mm Hg,
P=.001). Two patients developed presyncope during erect
cycle exercise associated with documented exercise-induced
hypotension. Both had previously given a history of syncope or
presyncope on exercise.
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As Table 2
and Fig
2 show, the patients exhibited an
attenuated reduction in corrected splenic counts during exercise
compared with control subjects (-15.8±21.7% versus
-42.6±12.6%, P<.0001). Three patients exhibited an
increase in counts during exercise, a response not seen in any control
subjects. An abnormal exercise splenic venous response was defined as
an increase in counts during exercise or a decrease of 
30% (ie, 1 SD
below the mean of the control group). On this basis, only 5 patients
exhibited a normal response.
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Right Atrial Pressure Measurements
The attenuated fall in
splenic venous volume during exercise in
patients might reflect either impaired venoconstriction or a movement
along the same venous pressure-volume relation resulting from an
increase in splenic venous pressure during exercise in patients. To
assess the latter possibility, 5 patients who exhibited abnormalities
of splenic venous volume change on the initial test (-25.2%,
-12.9%, -10.9%, 7.9%, and 28.4%) underwent another
upright cycle exercise test with measurement of right atrial pressure
at rest and during the same maximal workload as in the initial test and
were compared with 5 of the control subjects studied at rest and at
peak exercise. During exercise, right atrial pressure fell by 2 to 7 mm
Hg (mean, 4.3 mm Hg) in the patients; in the control subjects, right
atrial pressure changed by -4 to 2 mm Hg (mean, 0 mm Hg;
P=.05). This implies that the attenuated reduction in
splenic venous volume during exercise in patients reflects a failure to
increase venous tone.
Measurement of Forearm Blood Flow During Semierect Exercise
Testing
Semierect exercise was completed without complication in all
patients. As Table 3 shows, heart rates at rest and at
peak exercise were similar in the two groups, although mean blood
pressure tended to be slightly lower at peak exercise in patients
versus control subjects (116±18 versus 127±17 mm Hg,
P=.1). FVR was similar at rest in patients and control
subjects but decreased by 2±32% in patients and increased by
108±90% in control subjects during exercise (P<.0001).
FVR fell during exercise in 16 of the 25 patients, a response seen in
only 1 control subject.
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Relation Between Exercise Splenic Venous Volume and Changes in
Exercise Forearm Venous Responses
For both the patient and control
groups, the percentage change in
splenic venous volume was not related to the percentage change in FVR
(r=-.06, P=NS and
r=-.18,
P=NS, respectively).
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Discussion |
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The important new finding of this study is that patients with vasovagal syncope exhibit a normal increase in forearm venous tone during subhypotensive LBNP but markedly impaired reductions in splenic venous volume (and in 3 patients, paradoxical increases in splenic venous volume) during exercise. Assessment of right atrial pressure in a subset suggests that the latter reflects a failure to increase splenic venous tone on exercise. There was also a failure of constriction of resistance vessels in nonactive muscles, but the percentage changes in splenic volumes and FVR were unrelated.
Is the Vasovagal Response Caused by a Failure of Reflex
Venoconstriction?
Almquist and coworkers2 proposed that
vasovagal
syncope is a consequence of left ventricular
mechanoreceptor activation in the setting of an underfilled
hypercontractile ventricle. Hemorrhage experiments in conscious
rabbits were initially thought to support this concept. With
progressive hemorrhage, there is initial
tachycardia and increased renal sympathetic nerve activity
(phase 1), but when blood volume decreases by 30% and cardiac
output by 50% in this model, renal sympathetic nerve activity and
heart rate both decrease (phase 2), a phenomenon analogous to the
vasovagal response.6 This phase can be blocked by
intrapericardial procaine,20 leading to the suggestion
that left ventricular mechanoreceptor activation is solely
responsible. However, a recent report demonstrated that vagotomy does
not always completely abolish phase 2, although the onset is
delayed.6 Similarly, vasovagal responses have been
reported during aggressive tilt table protocols in cardiac transplant
recipients in whom there is cardiac vagal
deafferentation.7 Thus, left ventricular
mechanoreceptor activation probably is not the sole mechanism of the
vasovagal response. Dickinson8 recently suggested that
collapse firing of cardiopulmonary receptors at the
junction of the atria and the great veins may be responsible. It seems
likely on balance that firing of one or more groups of
cardiopulmonary mechanoreceptors may be at least partly
responsible for the vasovagal response. The observation of greater
decreases in left ventricular end-diastolic
volume and greater increases in ejection fraction during tilt testing
in patients with vasovagal syncope compared with control subjects is
consistent with an exaggerated decrease in cardiac volume as
the mechanism,9 10 11 perhaps because of
abnormal local left
ventricular wall stresses.21 This leads to the
hypothesis that a failure of appropriate reflex venoconstriction during
postural stress may result in an exaggerated decrease in cardiac
volume, the enhanced epinephrine response, which has been
demonstrated in patients with vasovagal syncope,22 and
finally paradoxical cardiopulmonary mechanoreceptor
activation. One group previously showed that patients who become
syncopal on head-up tilt have greater increases in calf venous
volume during tilt testing and less variability in the venous volume
during the tilted period.23 Another group demonstrated
impaired forearm venoconstrictor responses during mental arithmetic
stress,24 lending support to this concept.
In this study, we evaluated whether forearm venous tone increased normally during application of minor (subhypotensive) LBNP. Forearm venoconstriction was similar in patients and control subjects, although the observation of paradoxical venodilation during subhypotensive LBNP in 1 patient warrants further investigation in a large series and may suggest occasional individuals in whom a primary failure of venoconstriction during LBNP might occur. We demonstrated previously that during subhypotensive LBNP, impaired forearm constriction or paradoxical vasodilation of resistance vessels is present,25 implying that although hypotension has not developed, the vasovagal reaction may have already begun. The patient population for this earlier study had considerable overlap with the population in the present study. Similarly, Sneddon et al5 demonstrated impaired constriction of forearm resistance vessels after only 2 minutes of head-up tilt in patients with vasovagal syncope. Conversely, it must be noted that this group demonstrated exaggerated constriction of forearm resistance vessels during minor subhypotensive LBNP in patients with vasovagal syncope.26 Nevertheless, given the fact that our patient populations in the venous and resistance vessel studies are largely the same, it is reasonable to conclude that normal forearm venoconstriction is occurring at a stage when impaired constriction or dilation of resistance vessels is present. This makes it unlikely that a failure of venoconstriction during central volume unloading is the initial trigger for the vasovagal reaction. Despite this, venodilation may be an important contributory mechanism in other situations. As Manyari and Sheldon24 demonstrated, forearm venoconstriction is impaired during mental arithmetic stress. Similarly, a loss of venous tone is likely to occur with the onset of the vasovagal reaction and may then lead to a vicious circle of left ventricular volume reduction and hence aggravation of the vasovagal response.
Splenic Venous Capacitance During Exercise
We previously
reported that exercise syncope in patients with
normal hearts may be a variant of vasovagal syncope.13
Furthermore, we recently demonstrated that patients with vasovagal
syncope exhibit impaired constriction or paradoxical dilation of
forearm vessels during dynamic leg exercise.12 This
suggests that reflex vascular control mechanisms may be abnormal during
exercise in patients with vasovagal syncope. In this study, we tested
the hypothesis that there is failure of reflex splenic venoconstriction
during exercise in patients with vasovagal syncope. In normal subjects,
there is a marked reduction in splanchnic and splenic venous
capacitance during exercise.14 This may be an important
mechanism of augmenting stroke volume in the face of a reduced
diastolic filling time associated with sinus
tachycardia. Our data suggest that there is a markedly
attenuated reduction in splenic venous volume (and in 3 patients, a
paradoxical increase) during exercise compared with control subjects.
Simultaneous measurement of right atrial pressure during
exercise in a subset of patients and control subjects suggests that
this represents a failure of active venoconstriction rather
than passive venous volume changes.
Mark et al27 28 proposed that the abnormal vasodilator response seen in forearm resistance vessels during dynamic leg exercise in patients with aortic stenosis may be due to exaggerated left ventricular mechanoreceptor activation. Our observation of abnormal forearm resistance vasodilatation during exercise in patients with vasovagal syncope may have a similar basis, as may our previous observations about ischemic heart disease29 and hypertrophic cardiomyopathy.30 31 The mechanism of splenic and splanchnic venoconstriction during exercise is unclear. It may also be a consequence of exaggerated left ventricular mechanoreceptor activation, but this is speculative. Cardiac distension decreases venous tone presumably by activation of left ventricular mechanoreceptors.32 33 34 Stimulation of chemosensitive left ventricular receptors by intracoronary prostacyclin decreases intestinal venous tone.35 The recent observation of a marked decrease in splanchnic venous tone during phase 2 in the animal hemorrhage model described above is consistent with venodilation as a consequence of the vasovagal phenomenon36 but does not necessarily prove that it is due to left ventricular mechanoreceptor activation.
The lack of a relation between changes in splenic venous volume and FVR during exercise in both patients and control subjects, while not inconsistent with ventricular mechanoreceptor activation as the mechanism of the failure of venoconstriction in patients, may imply that the control mechanisms for the venous capacitance and resistance vessels during exercise are not identical. Given the known differences in hemodynamics in normal subjects and patients with cardiac disease during exercise in the supine versus erect position, the difference in exercise protocols (semierect cycle for the FVR studies versus erect cycle for the venous studies) dictates some caution in this conclusion.37 38 However, we have demonstrated that in normal subjects, the change in FVR is similar during semierect (70° to horizontal) versus supine exercise.39 The difference in forearm vascular response during supine cycle exercise at 70° to horizontal and erect cycle exercise is likely to be less than the difference between semierect and supine exercise.
Study Limitations
Although this study demonstrates forearm
venoconstriction to be
normal during application of subhypotensive LBNP in patients with
vasovagal syncope, we cannot exclude a failure of venoconstriction in
the quantitatively more important splanchnic and splenic venous beds.
Imaging of splenic venous volume in the LBNP bed proved technically
impossible, and intubation of the splenic vein to assess venous
pressure-volume relations rather than volume alone was not
ethically feasible.
One of the primary problems with this investigation is the different exercise protocols used to assess changes in splenic venous volume and changes in FVR. It was technically not possible to assess splenic venous volume on the semierect cycle because the spleen is best imaged posteriorly and the semierect cycle interferes with that imaging. Conversely, forearm vascular responses could not be obtained with any accuracy during erect cycle exercise because increased movement artifact in this position renders the traces unreadable. The exercise stages were also of slightly different lengths (4 versus 3 minutes). While conceding this limitation, as outlined earlier, we believe there is still some validity to comparing vascular responses during the two forms of exercise.
Conclusions
There is a failure of reflex constriction or
paradoxical dilation
of both resistance and venous capacitance vessels during exercise in
patients with vasovagal syncope, and this may lead to
exercise-induced hypotension in some patients. The mechanism of
this abnormality of reflex vascular control during exercise remains
speculative. Reflex venoconstriction during subhypotensive LBNP was
normal.
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Acknowledgments |
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This work was supported in part by grants from the NH&MRC of Australia (project grant number 665 941193, scholarship number 948220).
Received August 1, 1995; revision received September 27, 1995; accepted October 1, 1995.
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References |
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