Case Reports

Primary Pulmonary Hypertension

Effect of Unilateral Pulmonary Artery Occlusion

and Infusion of Acetylcholine*

BERNARD L . CHARMS, M .D .
Cleveland, Ohio

NCREASED PULMONARY vascular tone has been
I suggested as an important factor in the
etiology and pathogenesis of primary pul-
monary hypertension and the ensuing right
ventricular hypertrophy and failure .'-1 Patho-
logic changes observed are all compatible with
pulmonary hypertension due to any cause
All attempts at treatment with hypotensive
drugs or by surgical means have failed to
alter the inexorable course of the disease .',',' I
A method for lowering the high pulmonary
vascular resistance present, similar to that used
in systemic hypertension, would be obviously
desirable if the pulmonary blood vessels were
still reactive .
Utilizing the method of temporary unilateral
pulmonary arterial occlusion in patients with
pulmonary hypertension due to mitral stenosis
or cardiac failure,' or chronic pulmonary
disease,' a marked decrease in arteriolar
resistance was observed in the unoccluded
lung . In these studies sudden release of tone
was produced despite very high initial re-
sistances .
Recently, acetylcholine has been shown to
lower pulmonary artery pressure when injected
directly into the pulmonary artery at a dosage
level which would not affect systemic pressure .'
When infused at a suitable constant rate into
the pulmonary artery, a decrease in pressure
and vascular resistance occurs in normal
subjects and this reduction is accentuated when
the pulmonary artery pressures are raised by
hvpoxia .'o'1' In patients with pulmonary
* From the Hexter Cardio-Pulmonary Laboratory, Mount Sinai Hospital of Cleveland, Cleveland, Ohio . Aided by
grants in aid from the Cleveland Area Heart Society .
hypertension secondary to mitral valvular
disease the effect is even more striking .''-14
Wood et al 12 also noted a marked reduction of
pressure in patients with primary pulmonary
hypertension .
It is the purpose of this communication to
.' report the results of temporary unilateral
pulmonary artery occlusion and infusion of
acetylcholine in a patient with primary pul-
monary hypertension proved by cardiac cath-
eterization and pulmonary biopsy .
CASE HISTORY
This twenty-nine year old Negro woman was ad-
mitted to the hospital with a two week history of
progressive swelling of the abdomen and edema of
the face and extremities, weakness and faintness nn
effort . Slight systemic hypertension had been noted
during pregnancy two years prior to admission .
On physical examination, the arterial blood pres-
sure was 160/110 mm . Hg, the pulse was 96 per
minute and regular, respirations 16 per minute and
temperature 98 .8F . The significant findings in-
cluded edema of the face, liver edge palpable 3
fingcrbreadths below the right costal margin, signs of
abdominal fluid and 3 plus pitting edema of the ex-
tremities . A soft diastolic murmur was heard to
the left of the sternum in the third and fourth inter-
costal spaces and, at times, a systolic murmur was also
audible, The pulmonic second sound was tambouric
and split . The lungs were clear .
Roentgenogram of the chest and an electrocardio-
gram showed right ventricular hypertrophy (Figs . 1
and 2) . Results of ventilatory function studies were
within normal limits .
She was treated with digitalis and mercurial diuret-
94 THE AMERICAN JOURNAL OF CARDIOLOGY
 Primary Pulmonary Hypertension
Pte . 1 . Chest roentgenogram.
ics and showed an excellent response with a fourteen
pound weight loss . Lung biopsy revealed some evi-
dence of pulmonary vascular disease (Fig . 3) but most
sections were normal .
METHODS
Cardiac catheterization was carried out in a rest-
ing postabsorptive state . Pulmonary function studies
had been performed on the previous day to acquaint
the patient with laboratory surroundings and per-
sonnel . No premedication was given . A special
triple lumen catheter was used with an inflatable cuff
on the middle lumen as previously described .'' The
catheter was positioned fluoroscopically in the right
main pulmonary artery so that the proximal lumen
lay iust beyond the pulmonic valve and the cuff just
at the root of the right main pulmonary artery . An
indwelling arterial needle was placed in the brachial
artery for measurements of pressure and sampling of
arterial blood . A polyethylene tube with lead
sinker r%-as placed fluoroscopically in the esophagus at
the level of the seventh thoracic vertebra for measure-
ment of esophageal (i .e ., intrapleural) pressures . 1 '
After resting twenty minutes control values were
obtained . Pulmonary wedge pressure could not be
obtained . Pulmonary arterial pressure was obtained
by a Sanborn electromanometer and brachial and
esophageal pressures measured via Stathamn strain
gauges . Respiratory minute volumes were deter-
mined by collection of expired air in Douglas bags for
ten minute periods and oxygen consumption and
respiratory quotients determined by analysis on a
Scholander 0 .5 cc . gas analyzer . Blood samples were
analyzed by the spectrophotometric method of
Huckabeell and by Van Slyke manometric tech-
Jot y 1961
95
Ftc . 2. Routine electrocardiogram.
nics .'s Cardiac output was determined by Fick
principle and pulmonary vascular resistance calcu-
lated from standard formulas . The wedge pressure
was not obtained ; therefore, the pressure distal to
occlusion was used as pulmonary wedge pressure .
This distal pressure has been identical with wedge
pressures .''
After control values were obtained, the cuff in
the right main pulmonary artery was inflated under
fluoreseopic control with 35 per cent Diodrast
However, the catheter was pulled distally and
probably occluded only the right middle and lower
lobes . No symptoms ensued and after fifteen minutes,
repeat studies were obtained . the cuff was then
deflated and, after the pressures were stabilized, an
infusion of acetylcholine, 0 .5 mg . per tninute. into
the main pulmonary artery was begun . After
fifteen minutes of infusion repeat studies were again
obtained .
RESULTS
The findings of cardiac catheterization are
listed in Table r . Severe pulmonary hyper-
tension and slight systemic hypertension were
noted . The control cardiac output, arterio-
venous oxygen difference and peripheral oxygen
saturation were within normal limits . The


96 Charms

Fm. 3 . Biopsy specimen of lung showing some degree of pulmonary arteriolar disease.

TABLE I
Catheterization Findings

Arterial
Pressures (mm . Hg) Oxygen

Effects Pulmonary Artery Brachial artery Esophageal

Capacity
Inspira- Expira- (vol . %)
S I D M Distal S 1) N1 tion tion -

Control 100 65 74 150 105 122 -5 0 15 .6

Occlude right, middle and lower lobes 106 70 177 130 105 117 -5 -1 15 .6
Acetylcholine infusion (0 .5mg ./min.) 42 20 35 150 110 130 -3 0 15 .6

Nom : Right ventricular pressure, 100/5 (mean pressure, 48) . S = systolic ; D = diastolic ; M = mean .

THE AMERICAN JOURNAL OF CARDIOLOGY



Primary Pulmonary Hypertension 97

markedly elevated pulmonary arteriolar re- COMMENTS

sistance is evident .
Following occlusion of the arteries to the
right middle and lower lobes, a slight incre-
ment in main pulmonary arterial pressure
occurred while the peripheral arterial pressure
fell (Fig. 4A) . No change was noted in
esophageal pressure . The pressure beyond the
occluding cuff fell to wedge levels as previously
described . Peripheral oxygen saturation re-
mained within normal limits . However, the
arteriovenous difference increased and cardiac
output fell slightly . Although the total cal-
culated pulmonary arteriolar resistance ap-
parently increased, the actual resistance of the
perfused lung had decreased by at least one-
third since the total perfusion of the lungs was
now proceeding via the left lung and upper
lobe of the right lung only .
With infusion of acetylcholine, a striking de-
crease was noted in pulmonary artery pressure
and at the same time a sharp transient rise in
systemic pressure with gradual return to
control levels (Fig . 4B) . Esophageal pressure
and heart rate were unchanged and only a
transient decrease in respiratory rate took place .
Systemic arterial oxygen saturation fell and
cardiac output rose . Marked decrease in
pulmonary arteriolar resistance was evident .
After cessation of the infusion, the pulmonary
artery pressure returned to control levels within
fifteen minutes .
As we have demonstrated previously, many
patients with pulmonary hypertension due to
cardiac or pulmonary disease can withstand
occlusion of one main pulmonary artery with-
out change in cardiac output or pulmonary
artery pressure . 7 's This was also true in this
instance although some fall in cardiac output
and systemic pressure did occur, indicating
incomplete release of tone and fall in resistance
of the perfused lung .
Infusion of acetylcholine evoked profound
decrease in pulmonary arterial pressure and
arteriolar resistance . The only change in
systemic vascular pressure was a temporary
increase due to the abrupt release of pulmonary
arteriolar tone and the increased cardiac output .
No change in heart rate or respiratory rate
occurred, emphasizing the absence of systemic
effect . The action of the drug seems to be
directly on the pulmonary arterioles, as sug-
gested by Wood et al ." and Soderholm and
Werkol' The fall in arterial oxygen saturation
was noted in the present study and coincides
with other reports ." It seems likely that the
augmented pulmonary blood flow and release
of tone of vessels perfusing poorly ventilated
alveoli resulted in venous admixture in the
lung and systemic hypoxemia .
This patient is of particular interest because
of the evidence of high degree of tone of the
pulmonary vessels with very little demonstrable

TABLE I (Continued)

Arterial
Oxygen
A-V Os Respiratory Cardiac Pulmonary
0, Concen- Minute Cardiac
Respiratory Output Index Arteriolar
Per Cent Difference tration Volume Quotient (L./min Resistance
Content (vol. %) (cc ./min.) (L ./min .) (L./min .) ./ (dynes sec.
Satura-
(vol .%)
% tion cm - s)

14 .5 93 4 .1 193 6 .9 0 .97 4 .7 3 .1 1153

14 .5 93 5 .1 226 8 .1 0 .94 4 .4 2 .9 1311
13 .8 89 4 .0 209 6 .8 0 .89 5 .2 3 .4 463

R = PA M - LAM X 1332 X 60 s ec.

C O X 1000 cm .s

JULY 1961
98 Charms

B
Fin . 4 . A, effect of occlusion of right middle and look' lobe branches of pulmonary artery, on pulmonary artery,
brachial artery and esophageal pressures . B, effect of infusion of acetylcheline, 05 mg . per minute, directly into main
pulmonary artery on pulmonary artery, brachial artery and esophageal pressures .

histologic change . It is suggested that the
increase in tone is the primary difficulty in
this disease and that the pathologic changes
are secondary to long-standing pulmonary
vasospasm . The mechanism of the increased
tone is as yet unexplained .
and pulmonary arteriolar resistance without
any systemic effects, suggesting direct action of
the drug on the pulmonary arterioles .
It is suggested that, in this case, increased
tone is the primary defect and the histologic
vascular changes secondary .

SUMMARY
A case of primary pulmonary hypertension is
presented with evidence of increased vascular
tone . Temporary unilateral occlusion of right
middle and lower lobes caused a decrease in
estimated arteriolar resistance of unoccluded
lung . Infusion of acetylcholine caused a
profound decrease in pulmonary artery pressure
ACKNOWLEDGMENT
I wish to express my gratitude to Drs . P . M . Kohn,
T. Inoue, and Miss J. Wood and MMrs . M. Strauss for
their assistance in this work .
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THE AMERICAN JOURNAL OF CARDIOLOGY


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