Download Paroxysmal Hypotension Associated with Sympathetic

PAROXYSMAL SYMPATHETIC WITHDRAWAL/Williams and Bashore
901
22. Caldwell PD, Ricketts HJ, Dillard DH, Guntheroth WG: Ventricular tachycardia in a child: an indication for angiography?
Am Heart J 88: 777, 1974
23. Engle MA, Ebert PA, Redo SF: Recurrent ventricular
tachycardia due to resectable cardiac tumor. Circulation 50:
1052, 1974
tachycardia and ventricular fibrillation in a young population.
Circulation 60: 988, 1979
21. Ferrer PL: Arrhythmias in the neonate. In Cardiac
Arrhythmias in the Neonate, Infant and Child, edited by
Roberts, NI, Gelband H. New York, Appleton-CenturyCrofts, 1977, p 291
Paroxysmal Hypotension Associated
with Sympathetic Withdrawal
A New Disorder of Autonomic Vasomotor Regulation
R. SANDERS WILLIAMS, M.D.,
AND
THOMAS M. BASHORE, M.D.
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SUMMARY We evaluated a patient who had transient episodes of hypotension with clinical and laboratory
features apparently distinct from previously recognized disorders of vasomotor regulation. In between his
abrupt attacks of hypotension, the patient is asymptomatic and demonstrates normal autonomic modulation of
heart rate and blood pressure in response to changes in body position, Valsalva maneuver, cold, and exercise.
During periods of hypotension, his plasma norepinephrine falls markedly and he has blunted or absent
responses to stimuli that normally have a pressor effect due to sympathetic efferent discharge. Mechanical or
known hormonal disorders that produce episodic hypotension have been excluded by extensive testing. We
suggest two possible causes for our patient's paroxysmal sympathetic withdrawal: first, a centrally mediated
inhibition of sympathetic discharge to peripheral resistance and capacitance vessels, but with no afferent
stimulus reflexly producing sympathetic withdrawal readily evident; or second, an episodic release of an unknown endogenous compound with inhibitory effects upon central or preganglionic sympathetic neurons or
upon postganglionic sympathetic neurons by a presynaptic inhibition of norepinephrine release.
HYPOTENSION associated with abnormal autonomic modulation of vasomotor function is a prominent feature of several neurologic disorders-117 (table
lA). Other disorders may also lead to paroxysmal
hypotension by one of three major mechanisms:
episodic or variable vascular obstruction,18 22 abnormal activation of vasodepressor reflexes,23 26 or abnormal episodic release of endogenous vasoactive substances27-32 (table 1B).
We recently evaluated a patient with paroxysmal
hypotension in whom extensive laboratory investigation revealed features that appear to be distinct from
any recognized disorders of vasomotor regulation.
Case Report
A 50-year-old Caucasian man was referred to our
Cardiovascular Laboratory for the evaluation of frequent episodes of presyncope associated with hypotension. His spells of lightheadedness occurred one to
three times daily and lasted 1 minute to 4 hours. He
From the Division of Cardiology, Duke University Medical
Center, and the Veterans Administration Medical Center, Durham,
North Carolina.
Address for correspondence: R. Sanders Williams, M.D., P.O.
Box 3945, Duke University Medical Center, Durham, North
Carolina 27710.
Received November 21, 1979; revision accepted March 5, 1980.
Circulation 62, No. 4, 1980.
had to remain supine to avoid syncope. The onset of
the spells was not related to body position. There were
no premonitory symptoms, no apparent periodicity,
and no evident precipitating events (such as exertion,
meals or emotional stress) associated with the
episodes. He occasionally had bitemporal headaches
during or after a period of hypotension, but had no
other associated symptoms. He had no flushing of the
skin. In between the episodes he was asymptomatic,
with no orthostatic lightheadedness or abnormalities
of sweating or micturition.
He first noted similar spells in 1971, though from
that time until late 1978 they had been less frequent
(one or two per month) and were shorter (5-60
minutes) than the more recent spells. Previous
therapeutic trials of ephedrine, atropine and
fludrocortisone acetate had been ineffective in preventing or moderating his symptoms.
His medical history included numerous episodes of
superficial and deep thrombophlebitis of the lower extremities, dating from a deep-vein thrombosis during
hospitalization for an appendiceal abscess at age 12
years, and including several vein-stripping procedures.
In 1971 he suffered an angiographically documented
pulmonary embolus despite systemic anticoagulation,
and underwent percutaneous insertion of an umbrella
filter device33 into his inferior vena cava. He also had a
history of abuse of alcohol and minor tranquilizers
and reported several hospital admissions for psy-
CIRCULATION
902
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TABLE 1. Disorders of Vasomotor Control Leading to Hypotension
A. Neurologic disorders associated with autoiiomic dysfunction
Peripheral neuropathies: diabetes mellitus;2 alcoholism;3
acute intermittenit porphyria; 4 tabes dorsalis5
Wernicke's disease6
Parkinson's disease7
Holmes-Adie syndrome8
Familial dysautonomia (Riley-Day)9
Lesch-Nyan syndrome'0
Guillain-Barre syndrome"1
Shy-D)rager syndrome12 aiid idiopathic orthostatic hypotensionl3
Acute pandysautonomia14
Autonomic epilepsy1"
Old age"6
Postprandial glucose loading17
Numerous drugs with hypotensive effects
B. Disorders producing episodic hypotension (excluding
cardiac dysrhythmias)
IJtermittent vascular obstruction
Atrial myxomals
Defective cardiac valve prosthesisl9
Pregnancy or large iiitra-abdomiiial tumor2'
Aortic stenosis21
Idiopathic hypertrophic subaortic steniosis (IHSS)22
Abnormal activation of autoniomic reflexes
Centrally mediated vasodepressor syncope23
Hypersensitive carotid sinus syndrome24
Micturition syncope2'
Cough syncope26
? Aortic stenosis2l and ? IHSS22
Abnormal release of vasoactive substances
Pheochromocytoma (epinephrine, dopamine, other
amines)27
Carcinoid syndrome (serotonin)28
Systemic mastocytosis (histamine)29
Anaphylactic shock (histamine, kiniins, SR1S-A);°
Septicemic shock (endotoxins)31
Hereditary angioedema (complement activation)12
chiatric evaluation and care. Although he denied
alcohol or drug abuse in the 3 months before admission, he did note prominent symptoms of depression.
He also gave a history of hypertension that had intermittently been treated with diuretics.
On physical examination he weighed 235 lbs and
was 5'10" tall. His supine vital signs were pulse rate 72
beats/min and blood pressure 150/90 mm Hg, changing normally with standing to a pulse rate of 76
beats/min and blood pressure of 142/90 mm Hg. During a typical hypotensive spell (fig. 1) his blood
pressure fell precipitously, to a range of 50/30 mm Hg
to 80/50 mm Hg, usually with no change in heart rate
or a slowing to a range of 48-68 beats/min. His
periods of hypotension during hemodynamic monitoring ranged from 3 minutes to 21/2 hours. During
hypotension he remained oriented and conversant,
VOL 62, No 4, OCTOBER 1980
though at times he appeared drowsy; his extremities
remained warm; he did not become diaphoretic; his
pupils were midposition and his pupillary responses to
light were preserved; and his respiratory rate generally
increased slightly, although he had no striking
hyperventilation.
His skin showed stasis hyperpigmentation of the
lower extremities. His head, eyes, ears, nose and
throat were normal. His jugular venous pulsations
were normal, as was his thyroid gland. He had
bilateral carotid bruits, which were more prominent
on the left. His left ventricular impulse was in the fifth
left intercostal space, 12 cm from the midsternal line,
and was normal. S, and S, were normal, and an S4
gallop was present. No cardiac murmurs or other abnormal sounds were present. His lungs, abdomen, rectum, and genitalia were normal. The lower extremities
showed superficial varicosities and 1 + peripheral
edema. The peripheral arterial pulsations were normal. His neurologic examination was within normal
limits.
Baseline laboratory data included a chest
radiograph that was normal except for some calcification in the aortic knob and an ECG that showed nonspecific ST-T-wave changes only. His ECG was unchanged during hypotension. A complete blood count,
urinalysis, serum electrolytes, urea nitrogen, blood
sugar, and SMA-12 were within normal limits, except
for a uric acid of 8.7 mg%. His prothrombin time was
12.3 seconds (control 11.8 seconds). Partial thromboplastin time was 32.3 seconds (control 39.8 seconds).
Other laboratory data included erythrocyte
sedimentation rate (Westergren) 38 mm/hour fluorescent antinuclear antibody titer 1:160 with weakly
speckled pattern, VDRL negative, hepatitisassociated (surface) antigen negative, rheumatoid factor negative, LE prep negative, thyroxine 9.8 mg/100
ml, RT3U 27%.
Radioisotope quantification of plasma volume by
1251-albumin was within normal limits. Plasma cortisol
was normal. A toxic screen of plasma at the time of
admission revealed only trace levels of benzodiazepine
metabolites. Urinary excretion per 24 hours of 5HIAA was undetectable, and of VMA was normal at
3.4 mg. Computerized axial tomography of the abdomen was normal.
Laboratory Evaluation of Hypotensive Episodes
The hemodynamic characteristics of our patient's
hypotensive episodes were studied in the cardiac
catheterization laboratory and by continuous hemodynamic monitoring on the coronary care unit. Recordings of intra-arterial blood pressure during normotension and during typical hypotensive episodes are
shown in figure 1. Hemodynamic measurements obtained in the catheterization laboratory before and
during a hypotensive spell are listed in table 2. The initial pulmonary capillary wedge pressure of 18 mm Hg,
observed in the catheterization laboratory, followed
the injection of radiographic contrast media; more
typical measurements during continuous hemo-
PAROXYSMAL SYMPATHETIC WITHDRAWAL/ Williamis and Bashore
AE
CONTROL
903
DECREASED BP
Spontaneous BP Fall
ECG
200r
ARTERIAL
PRESSURE
100
(mm Hg)
N...
HR 65
,W
0t
1 Sec.
B
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ARTERIAL PRESSURE
(mm Hg)
100
0-
1 Min.
Frc RF. 1. Intra-arterial pressure recordings during hypotenivive epis odes. (A ) Hrpoten.is ive episode iin the
catheterization laboratory. Tracings are not continuous. (B) Continuous miioni.toring of radial arteriy
pressvre. This tracing illustrates the typical abrupt swings in blood pressure. front normotension at left to
profound hripotension,followed bir a rapid return to normotension again. BP blood pressuare; IR - heart
rate.
dynamic monitoring on the coronary care unit during
normotension ranged from 8-14 mm Hg, and during
hypotension ranged from 5-8 mm Hg.
Injections of contrast media into the right atrium
revealed no evidence of right atrial myxoma, and no
left atrial filling defects were noted during levophase.
An echocardiogram was normal. Because we
suspected intermittent venous obstruction of the inferior vena cava at the level of his umbrella device,
pressure measurements above and below the umbrella
TA\BLE 2. Heniodlynamstl ic illeasurcuents Bcforc andIl)ring
Hypotensive Spell
Ilxoteinsion
Noinotenlsionilly
Arterial pressure (mrin Jig)
158 /4
78/46
a
hleart rate (bhets/naini)
Arterioveniouis oxygeni
differenlce (vol (()
58
158
5.4
6.6
5.8
2.5
100
4.0
t.7
Cardiac outpult, (Fick)
(/rnilln)
Cardiac inidex (1/ralilln lln2)
Stroke volume (nil)
Systemiic resistance
(Wood ullits)
Mean pulm-nonatry capillary
wedge pressuire (mm lig)
16.4
18
69
11.5
8
made and contrast injections were performed
during normotension and during hypotension. There
was no pressure gradient, and dye flowed freely across
the umbrella during hypotension.
We tested our patient's responses to a number of
stimuli known to activate intrinsic autonomic
responses in normal subjects.1 Unlike his normal circulatory responses to changes in body position while
normotensive, during a hypotensive episode his blood
pressure fell still further with changes from the supine
to sitting position, evoking symptoms of presyncope,
and he failed to elevate his heart rate with sitting.
Valsalva maneuvers during normotension elicited
the expected fall in arterial pressure and tachycardia
during the late strain phase, followed by the normal
"overshoot" of blood pressure with slowing of the
heart rate upon release (fig. 2A). During hypotension,
these responses were markedly blunted (fig. 2B). The
adequacy of the Valsalva maneuver in each instance
was documented by a rise in intrathoracic pressure of
at least 40 mm Hg for at least 10 seconds as recorded
by a central venous catheter. Similarly, placing his
hand in ice water during normotension evoked the
were
normal pressor response (fig. 3A), while little effect
was noted during a hypotensive episode (fig. 3B).
Massage of either the left or right carotid sinus
produced bradycardia during normotension, but did
not produce hypotension; during hypotension, it
produced slight sinus slowing or had no effect.
(IOTBER 1980
Voi- 62, No 4,
CIlRCULATION
904
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Lr
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lOL
-----
c
--- VALSALVA
>1
4 Sec.
FIU REi 2. Intra-arterial pressure recordings during Valsuala maneuvers. (A J Valsalva m?anelul er dlurinig
normotension. A`Wte the prominent -overshoot of arterial pressure after the release of intrathoraci
.
(B) Valsalva maneuver during hvpotension. Note the absetnce ofthe -overshoot- phenomenon.
pressure
Plasma catecholanmines were measured by radioenzymatic assay34 on blood obtained from an indwelling venous needle left in place at least 15 minutes
before sampling. On 2 days, after blood samples were
obtained while the patient was supine and his blood
pressure was greater than 120/80 mm Hg, a hypotensive episode began. Repeat blood sampling was
done 5-15 minutes after the onset of a fall in arterial
pressure to levels less than 80/50 mm Hg. Each time
hypotension was associated with a fall in plasma
A.
200
..
,
5S
5~~
C)
~C EC
S~~
WATER IMMERSION --------------
POST
-
T-
E
FE
B.
LUJ
D
1i
LU
HR 55
a-
HR 45
HR 52
100k-1
4i
1 SEC
0-
PRE
ICE WATER IMMERSION
POST
[Iwt,'Ri, 3. Intra-arterial pressure recordings during immersion of the right hanid inz ice water. (A) Ice
water immersion during normotens ion. Note the rapid and sustained rise in arterial pressu4re. fllob wed hi a
retuirni to baseline after the cold stimiiulus was withdrawn. (Two nminutes elapse at the break ini the tracing. o
(B) Ice water immersi.on during hipotension. Note the absence of a significatt pressor effect. HR heart
=
rate.
PAROXYSMAL SYMPATHETIC WITHDRAWAL/ Williams and Bashore
300D
E
0
-c
,-z' lep(*.05
200.11
-
0
c
.a
.1
0
,'
.11
BP
Syst 120
100
(mm Hg)
Diast
1.1
,,1l~
C1
,
0
z
0
E
1.'
,
,
c
HR
(bpm)
0^ 100l
905
80
60
40
20)l
80
60
40
ICE
OFF
zu-
^L---i
U
--
40
80
120
160
Systolic Blood Pressure (Supine) (mm Hg)
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FIGURE 4. Plasma norepinephrine levels plotted against
the systolic blood pressure at the time of blood sampling.
Values during normotension are expressed as open squares
and values during hypotension as open circles. The dotted
lines connect determinations that were made serially within
1 hour of each other. The mean plasma norepinephrine during normotension (closed square) differed significantly from
the mean value during hypotension (closed circle) at the
p < 0.05 level by one-way analysis of variance. Vertical lines
represent the SEM.
norepinephrine to roughly one-half the resting value
(fig. 4).
An electroencephalogram with nasopharyngeal
leads was within normal limits during normotension
and was unchanged during a hypotensive episode.
Forearm venous plethysmography was monitored by
standard techniques35 before and during a hypotensive
episode, with results roughly paralleling the central
hemodynamics during cardiac catheterization.
Hypotension was associated with an abrupt fall in
forearm vascular resistance (fig. 5). When this occurred, ice placed on the forehead, perhaps a more potent sympathetic stimulus than placing the hand in ice
water, was associated with a slight, although blunted,
pressor response. During normotension, a bicycle
ergometer exercise test was unassociated with abnormalities in his ECG, and his heart rate and blood
pressure responses to exercise were normal. His ventricular function as assessed by gated blood pool
radionuclide angiography was normal both at rest and
with bicycle exercise.
Response to Cardiac Pacing, Pharmacologic
Agents and Biofeedback
Right atrial or right ventricular pacing (fig. 6) during a hypotensive episode did not correct the hypotensive state. Two types of drug studies were performed:
acute i.v. or intranasal drug administration during a
hypotensive episode aimed at correcting the hypotension and oral drug administration over a 72-hour
0
3
6
9
12 15 18 21 24 27 33 36 39
TIME (mins)
FIGURE 5. Heart rate (HR), bloodpressure (BP), forearm
blood flow (FBF) and forearm vascular resistance (FVR)
before and during a hypotensive episode. Note the rapid
decline in forearm vascular resistance occurring
simultaneously with the fall in systemic arterial pressure.
The application of ice to the forehead (arrow) produced a
rise in vascular resistance and a slight increase in arterial
pressure, though without returning arterial pressure to the
normal range.
period aimed at the prevention or modification of the
hypotensive spells. Because of the marked spontaneous variation in the duration of his hypotensive
spells, all acute interventions were performed several
times. Neither i.v. atropine (2 mg), propranolol (5
mg), or isoproterenol (4 ,g/min) produced a pressor
response during hypotensive episodes (fig. 6B and 6C),
although a cardioacceleratory effect of both atropine
and isoproterenol did occur. With i.v. phenylephrine
at an infusion rate of 75 ,ug/min, blood pressure
returned to or above the normal range each of the
three times it was tested (fig. 6D). A dose-response
effect was observed for phenylephrine in that lower
doses evoked smaller pressor effects. The doses of i.v.
phenylephrine necessary to produce a pressor response
were similar to those required for pressor effects in
normal subjects.`e Thus, we did not observe the hypersensitivity to infused catecholamines that may be present in patients with idiopathic orthostatic hypotension.37 Intranasal phenylephrine (1%) solution in doses
CIRCULATION
906
B=
EGG
E
E
PRE~ATROPINE
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Li
Er
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Ir
Li
FIGURE 6. Effects of cardiac pacing and drugs upon blood
during hypotension. ECG monitoring and radial
artery pressure (RA P) during hypotension before and during
right ventricular pacing (A), before and 5-10 minutes after 2
mg of i. v. atropine (B), before and during i. v. infusion of 4
g/mmin ofisoproterenol (C), and before and during i. v. infusion of 75 ,g/min of phenylephrine (D). The correction of
hypotension by phenylephrine was confirmed twice during
pressure
separate
hypotensive episodes.
as high as 5 mg was ineffective in correcting the
hypotension.
We attempted to prevent or modify our patient's
hypotensive episodes with a variety of pharmacologic
agents, with each drug administered orally in the
stated dosages for at least 72 hours. Neither carbamazepine 200 mg for 1 day, 400 mg for 1 day, then
600 mg every day for 3 days, indomethacin 25 mg
three times daily, ephedrine 25 mg four times daily,
the combination of diphenhydramine 50 mg three
times daily plus cimetidine 300 mg four times daily,
nor transylcypromine (monoamine oxidase inhibitor)
VOL 62, No 4, OCTOBER 1980
10 mg twice daily, induced any observable change in
the frequency, severity or duration of the hypotensive
episodes.
Biofeedback techniques and hypnosis were used to
find clues to possible centrally mediated factors
leading to his hypotensive episodes. Although a hypotensive spell occurred once during hypnosis, it could
not be reversed during or in the hour after hypnosis,
and voluntary induction or reversal of hypotension
could not be reproducibly accomplished on other occasions. The patient denied any voluntary control over
the episodes or any insight into psychological trigger
mechanisms. Surreptitious drug administration was
excluded by intra-arterial pressure recordings
documenting numerous typical hypotensive episodes
during sleep, during direct observation of the patient
in the catheterization laboratory, and during direct
visual monitoring of the patient by closed-circuit
television in the coronary care unit.
Discussion
Our patient's hypotensive episodes appear to be
different from previously reported disorders causing
hypotension. During periods of normotension, he
demonstrated normal autonomic vasomotor and cardiac chronotropic responses to standing, Valsalva
maneuver, cold and exercise. His periods of hypotension were associated with signs of dramatic
withdrawal of peripheral sympathetic efferent tone in
both resistance and capacitance vessels. During hypotension his total peripheral vascular resistance and
forearm vascular resistance fell markedly, his pulmonary capillary wedge pressure fell, he demonstrated
blunted or absent responses to maneuvers that normally activate sympathetic neural reflexes, and he had
an inappropriate bradycardia and an inappropriate
absence of cutaneous signs, such as pallor or sweating,
given the profound level of hypotension present. In addition, his plasma norepinephrine fell markedly with
the onset of hypotension, and the hypotension could
be readily corrected by i.v. phenylephrine, presumably
through its effect upon postsynaptic vascular aadrenergic receptors, but not by cholinergic antagonists, ,3-adrenergic agonists or antagonists, cardiac pacing, prostaglandin synthesis inhibitors,
histamine antagonists, monoamine oxidase inhibitors,
or antiepileptic medication.
We considered several possible causes for our patient's hypotensive spells. Anatomic loss of sympathetic neurons, inflammatory neuritis, or metabolic
abnormalities, such as diabetes mellitus leading to
autonomic insufficiency, were excluded by the highly
transient nature of the hypotensive episodes, the
absence of other neurologic dysfunction, and the
absence of discernible metabolic abnormalities. In addition, he had no other clinical evidence for the
neurologic disorders listed in table IA that have been
associated with hypotension. Centrencephalic epilepsy
causing stimulation of pathways inhibitory to the
peripheral release of norepinephrine was probably ex-
PAROXYSMAL SYMPATHETIC WITHDRAWAL/ Williams and Bashore
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cluded by the normal electroencephalogram during
hypotension and the lack of a therapeutic response to
carbamazepine.
Intermittent vascular obstruction at the site of his
inferior vena cava umbrella filter was excluded by
angiographic studies. There was no evidence for right
or left atrial myxoma, valvular heart disease, or
hypertrophic subaortic stenosis. In addition, intermittent vascular obstruction alone could not explain the
failure of the expected signs of reflex sympathetic
stimulation to appear with the onset of hypotension.
Abnormal release of vasoactive substances producing vasodilatation and episodic hypotension has been
observed in the situations cited in table 1 B, but plasma
or urine analyses, the failure of antagonist drug trials,
or the lack of other expected concomitant clinical
features excluded these known disorders.
The clinical and laboratory data suggesting episodic
withdrawal of peripheral sympathetic tone in association with our patient's hypotensive spells are strong.
However, the stimuli leading to sympathetic
withdrawal were not identifiable, unlike the common
form of vasodepressor syncope or the hypotensive syndromes of hypersensitive carotid sinus, micturition
syncope, or cough syncope. Also, the duration of his
hypotensive periods was often much longer than that
observed in these syndromes. There was no evidence
of a relationship between our patient's episodic hypotension and the other clinical abnormalities we
observed - the history of psychiatric disturbances,
the history of venous thromboembolic disease, the
carotid bruits, the elevated uric acid, and the moderate
antinuclear antibody titer.
We propose that one of two hypothetical
mechanisms leads to the apparent withdrawal of sympathetic tone that accompanies the episodic hypotension noted in our patient.
First, the withdrawal of peripheral sympathetic
vasomotor tone may be mediated centrally by reduced
firing of afferent neurons from the medullary
vasomotor centers. The primary stimulus that
produces this centrally mediated sympathetic
withdrawal could be from higher central nervous
system pathways impinging upon the vasomotor
centers of the brainstem, or from the activation of the
afferent limb of an undescribed vasodepressor reflex,
perhaps a sympathetically mediated analogy of the
vagally mediated Bezold-Jarish reflex38 in laboratory
animals. The opportunity to test this hypothesis must
await either identification of a stimulus that produces
hypotension in our patient or a method that allows us
to record the rate of afferent sympathetic neuronal firing in our patient.
Second, an apparent sympathetic withdrawal could
be produced by the episodic release of some unknown
endogenous compound, perhaps a tumor product,
with inhibitory effects either upon activation of central, pre- or postganglionic sympathetic neurons, or
upon the release of norepinephrine from postganglionic nerve terminals, perhaps by stimulation of
inhibitory presynaptic a-adrenergic receptors.
907
Acknowledgment
The authors gratefully acknowledge the assistance and advice of
Dr. John Baker and Dr. Jeffrey Medoff in the clinical evaluation of
the patient; Dr. Redford Williams for the forearm venous
plethysmography analysis and biofeedback efforts; Dr. Steven
Grossman, Dr. J. Caulie Gunnells and Robin Sykes for the plasma
catecholamine assays; and especially Dr. Joseph Greenfield and Dr.
Eugene Stead for their advice during the laboratory evaluation of
this patient and their review of the manuscript. We also thank Linda
Ashley and Janice James for their assistance in the preparation of
the manuscript.
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Paroxysmal hypotension associated with sympathetic withdrawal. A new disorder of
autonomic vasomotor regulation.
R S Williams and T M Bashore
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Circulation. 1980;62:901-908
doi: 10.1161/01.CIR.62.4.901
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