Download Pulmonary Venous and Arterial Hypertension due

Pulmonary Venous and Arterial Hypertension
due to Chronic Fibrous Mediastinitis
Hemodynamics and Pulmonary Function
By JAMES T. BOTTICELLI, M.D., DONALD P. SCHLUETER, M.D.,
AND
RAMON L. LANGE, M.D.
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ALTHOUGH chronic fibrous mediastinitis
is responsible for 8 to 23% of the cases
of superior vena caval obstruction,1-7 it may
also compress or obstruct other mediastinal
structures. Involvement of the tracheobronchial tree" 8, 9pulmonary artery,10-12 esophagus," 9, 13 aorta, and coronary arteries14 has
been reported. Obstruction of pulmonary veins,
however, is uncommon and may not be recognized as a cause of pulmonary hypertension.", 15-17
This report describes the clinical findings,
the abnormal hemodynamic and ventilatory
functions, and pathological material in a case
of complete or partial obstruction of the
superior vena cava, the bronchial tree, and
pulmonary veins with associated pulmonary
hypertension and diffuse interstitial fibrosis.
Repeated observations, including hemodynamic and pulmonary function studies, were made
over a 3-year period. The presumptive diagnosis of pulmonary vein obstruction secondary
to chronic fibrous mediastinitis was confirmed
by thoracotomy following which the patient's
condition has remained stable for 10 months.
vein distention and increasing shirt collar size.
Since age 21, he had been subject to frequent
"colds" characterized by cough productive of
clear sputum, dyspnea with exertion, and a sensation of chest "congestion" and heaviness.
The pulse rate on admission was 76, blood pressure was 108/80 mm Hg; respiratory rate, 16
and body temperature 99.6 F. The patient had a
"bull neck" appearance and markedly distended,
nonpulsatile neck veins. Collateral venous patterns were prominent over the anterior chest wall.
Inspiratory and expiratory wheezes were noted in
all lung fields, and the expiratory phase was prolonged. The heart size was normal. No murmurs
were heard, but fixed splitting of the second sound
at the base was noted along with accentuation
of the pulmonic closing sound. There was no
clubbing, cyanosis, or edema.
Hemoglobin concentration was 12.8 g per 100
ml. A serologic test for syphilis was nonreactive.
Sputum smears and cultures for acid-fast organisms were negative as were cultures for fungi.
The histoplasmin skin test caused a 4 + reaction,
but results of tuberculin tests with PPD and OT
and other fungal skin tests were negative. Complement fixation studies were nonreactive for
blastomycosis, coccidioidomycosis, and both the
yeast and mycelial phases of histoplasmosis. Electrocardiogram revealed right axis deviation and
right ventricular hypertrophy.
Slightly increased bronchovascular markings and
normal pulmonary artery were present on a routine chest x-ray taken in 1955. Chest x-ray
taken on admission showed marked increase in
bronchovascular markings with bilateral nodular
densities and partial atelectasis of the left lower
lobe (fig. 1 left). No evidence of major bronchial
obstruction was found at bronchoscopy. Esophogram and intravenous pyelography were normal.
A bronchogram of the left lung revealed compression of the left lower lobe bronchi with
some distal atelectasis (fig. 1 right).
The long duration of superior vena caval obstruction without evidence of malignant disease,
radiographic evidence of pulmonary fibrosis, and
right ventricular hypertrophy suggested a diagnosis of chronic fibrosing mediastinitis with asso-
Report of Case
R. B., a 35-year-old truck driver, was admitted
to the hospital on May 2, 1962, complaining of
severe hemoptysis. At age 18, he noted neck
From the Department of Medicine, Marquette
University School of Medicine, Milwaukee, Wisconsin.
Work was carried out during tenure of Dr. Botticelli as Advanced Research Fellow of the American
Heart Association.
This investigation was supported by U.S. Public
Health Service Grant HE-07434 and by National
Institutes of Health Research Grants HTS-5538 and
07488.
862
Circulation, Volume XXXIII, June 1966
FIBROUS MEDIASTINITIS
863
ciated pulmonary fibrosis and cor pulmonale.
Spirometric studies indicated moderately severe
ventilatory impairment, and cardiac catheterization and angiography confirmed the diagnosis of
pulmonary hypertension and superior vena caval
obstruction (tables 1 and 2).
The patient was discharged to the care of his
physician. He was readmitted on January 7,
1965, because of right lower chest pain and
dyspnea. He related that he had been able to work
only intermittently, as during the preceding 18
months, exertional dyspnea and easy fatigue had
increased.
The patient appeared acutely ill, cyanotic, and
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Figure 1
Left. Chest roentgenogram made in 1965. Diffusely increased interstitial markings and enlarged
pulmonary artery may be noted. Except for the right pleural effusion, there was no change
from 1962. Right. Bronchogram of left lower lobe made in 1962 demonstrates compression
of major bronchi and some atelectasis.
Table 1
Hemodynamic Data
Catheter position
Subelavian vein
Right atrium
Right ventricle
Pulmonary artery
Pulmonary artery wedge
Left atrium
Left ventricle
Femoral artery
Cardiac index, L/min/m2
Systemic vascular resistance
Total pulmonary resistance
Pulmonary postcapillary resistance
Pulmonary arteriolar resistance
*Mean pressure.
pressure.
tEnd-diastolic
Circulation, Volume XXXIII, June 1966
Pressure,
mm
Hg
1962
C02,
vol %
S02,
%
1965
C02,
vol %
S02,
78/0 4t
78/23 40*
9.08
56
18*
0*
14.12
88
14.33
3.25
21.2
12.3
5.5
6.8
89
Pressure,
mm
Hg
%
15*
3/0 2*
70/0
70/18 35*
4*
8.01
52.8
88/0 5t
100/58 72*
112.93
2.53
l8.00
85.4
105/56 72*
BOTTICELLI ET AL.
864
Table 2
Pulmnonary Function Studies
VC, L
FEV1, L
FEV1/VC, %
MVV, L/min
MMEF, L/sec
MEFRO.2-1.2' L/sec
Helium dilution
RV, L
TLC, L
RV/TLC, %
Predicted
Observed
4.61
3.72
>75
160
>2.2
>7.0
4.09
2.35
58
81
1.1
3.4
1962
% Predicted
88
-
-
57
-
1.41
6.02
23
Observed
1965
% Predicted
3.56
1.89
53
69
0.71
2.67
77
1.65
5.21
32
117
87
1.79
5.35
33
127
89
43
Plethysmographic
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RV, L
TLC, L
RV/TLC, %
1.41
6.02
23
1.87
5.96
31
132
99
Abbreviations: VC, vital capacity; FEV1, forced expiratory volume in 1 sec; MVV, maximum
voluntary ventilation; MMEF, maximum midexpiratory flow; MEFR, maximum expiratory flow
rate; RV, residual volume; TLC, total lung capacity.
dyspneic despite inhalation of oxygen. The
pulse rate was 96, blood pressure 120/80, respiratory rate 24, and temperature 98.6 F. Tender hepatomegaly was noted in addition to right
pleural effusion, rales, and expiratory wheezes.
Since the patient manifested severe dyspnea,
had a pleural transudate without generalized
anasarca, and had a history of hemoptysis, the
possibility of pulmonary venous obstruction due
to the adhesive mediastinal process was considered. Accordingly, hemodynamic and pulmonary
function studies were repeated.
Hemodynamic and Pulmonary Function Studies
Angiography was done in 1962. Following injection of contrast material into the subclavian
vein, marked collateral circulation was demonstrated, with no opacification of the superior vena
cava. Inferior vena caval injection revealed enlargement of the main pulmonary artery,
without evidence of constriction of major pulmonary arteries. In addition, reduced distribution
of contrast material was evident in the left lower
and in portions of the left upper lobe.
Hemodynamic studies from 1962 and 1965 are
presented in table 1. These confirm the presence
of superior vena caval obstruction since subclavian
vein pressure exceeded right atrial and inferior
vena caval pressure. Marked pulmonary hypertension without evidence of right heart failure
and normal cardiac output were found at the
time of both studies.
In 1965, the pulmonary artery wedge pressure
was 18 mm Hg in the left upper lobe and also
in the left lower lobe. The mean left atrial
pressure (transseptal technique) was 0. Since
the pressure gradient from the pulmonary artery
to the left atrium was 40 mm Hg and that from
the "pulmonary capillary" to the left atrium was
18 mm Hg, approximately half of the total pressure gradient, and therefore pulmonary vascular
resistance was located between the pulmonary
capillary bed and the left atrium. With exercise, a
marked increase in pulmonary artery (105/38 mm
Hg) and pulmonary artery wedge (31 mm Hg)
pressures occurred (figs. 2 and 3). At rest, only
slight variation in arterial systolic pressure was
seen despite considerable respiratory variation in
the pulmonary artery wedge pressure which was
not apparent in the left atrium. Aside from artifacts produced by catheter movement, the pulmonary artery wedge tracing lacked pulsatile
characteristics and did not resemble the left atrial
pressure. With exercise, considerably more respiratory variation could be seen in wedge and
arterial systolic pressures (fig. 2).
Indocyanine-green indicator-dilution curves
(fig. 4), following injection into the pulmonary
artery, revealed an 8-second appearance time and
normal contour. Injection into pulmonary artery
branches of the left upper and lower lobes resulted in indicator-dilution curves with appearance times corresponding to those obtained on
main pulmonary artery or inferior vena caval injection. However, there was marked prolongation
of the curve suggesting delayed washout of indi-
Circulation, Volume XXXIII, June 1966
FIBROUS MEDIASTINITIS
865
cator from the lung segments which had received
the bolus of indicator.
The results of pulmonary function studies are
shown in table 2, and are compatible with com-
5T
1
1
bined restrictive-obstructive ventilatory impairment of progressive severity. The lack of improvement with inhalation of isoproterenol in both
studies ruled out reversible bronchoconstriction.
1
I
1
1Tr
rv1
v7r
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Figure 2
Elevated pulmonary artery wedge pressure (PAW) with moderate respiratory variations may
be noted. With exercise, the wedge pressure rose from 18 to 31 while the femoral arterial
pressure also increased. Respiratory variation in pressure is present in the femoral arterial
tracing.
Figure 3
Pressure recording during pull back from left ventricle
to
left atrium demonstrates low atrial
and ventricular diastolic pressures with little respiratory variation.
Circulation, Volume XXXIJI, June 1966
BOTTICELLI ET AL.
866
gas studies (table 4) indicate slight arterial
unsaturation at rest (91%). With exercise, there
was a further decrease in arterial oxygen saturation to 89%, despite a considerable increase in
ventilation (02V 40). The carbon monoxide
diffusion capacity was reduced to 58% of the
predicted value.
1I
p
INSP
6
4Thdi
FeF
Sampk
Figr/I
Ar.
Operative Findings
4
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Figure 4
The indicator-dilution curve sampled from the femoral
artery following injection into the main pulmonary
artery has a normal cont.our. That following injection
into the left upper lobe segment, however, demonstrates nearly the same appearance time, but markedly delayed washout of indicator suggesting markedly diminished flow in the lung segment receiving
most of the injectate.
Marked abnormality of ventilation-distribution was
demonstrated since the dynamic lung compliance
was markedly decreased with respiratory rates
increasing from 25 to 160 per minute (table 3).
The nonelastic resistance (airway plus tissue)
was considerably elevated in inspiration and expiration. Both the elastic and nonelastic work
were moderately increased and could be related to the increased retractive force of the
lung due to fibrosis (elastic) and to the severe
airway obstruction (nonelastic). Arterial blood
The possibility that the pulmonary venous obstruction might be correctable led to surgical
exploration. Dense vascular adhesions were encountered and the superior vena cava was completely occluded throughout its entire length. The
lungs, which were firm and somewhat nodular,
failed to collapse. All right pulmonary veins were
severely narrowed in their extrapericardial segments. The lung parenchyma was woody hard
for 2 to 5 cm into the hilar region. Palpation of
the left hilum yielded similar characteristics. The
intrapericardial segments of pulmonary veins
were free from adhesions and collapsed partially
with each diastole. Insertion of a catheter into the
smaller radicles of the pulmonary veins via the
left atrial appendage revealed pressures as high
as 40 mm Hg in the smaller tributaries with
gradual reduction to 0 as the catheter was withdrawn into the left atrium. Since no operable
locus of venous obstruction was found, the procedure was terminated.
Biopsies of the pericardium and subpleural
areas of the right middle lobe showed an extreme
degree of fibrous thickening which, in some areas,
was markedly vascular. The pleural fibrosis extended into the interlobular and interalveolar
septa (fig. 5). Most of the vessels showed significant hypertrophy of the walls, and the smaller
branches of the pulmonary artery had an increased number of nuclei, indicating intimal
hyperplasia (fig. 6). Granulomata were not found
in the biopsy material, and treatment with meth-
Taible 3
Mechanics of Respiration
Static compliance, L/cm H20
Dynamic compliance, L/cm H20
Nonelastic resistance,
cm
H20/L/sec
Work of breathing, kg-m/min
Normal
1962
1965
0.22 0.05
0.18 + 0.04
0.19
0.16
1.5 -3.0
1.2
0.6
1.8
-
5.18*
-
25 bpm
43 bpm
100 bpm
120 bpm
160 bpm
Inspiration
Expiration
Elastic
Nonelastic
Total
0.139
0.115
0.094
0.077
0.022
6.41
9.03
3.92
3.72
7.64
*Interrupter method.
Circulation, Volume XXXIII, June 1966
867
FIBROUS MEDIASTINITIS
Table 4
Arterial Blood Gas Determinations
1962
Exercise
Predicted
so2, %
pCO2, mm Hg
pH
HCO3 mEq/L
02V
DLCO, cc/mm Hg/min
94
86
38
35 -44
7.38- 7.42
24 -30
25 -35
26
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enamine silver and Ziehl-Neelson stains failed to
reveal fungi or acid-fast organisms.
Postoperative convalescence was prolonged and
complicated by severe respiratory distress related to recurrent right pleural effusion. Chlorothiazide, digitalis, and low sodium diet were not
effective, and mercurial diuretics were required
along with occasional thoracentesis. Subsequently,
it was found that pleural transudation could be
prevented by aldosterone inhibition (Aldactone
A). During 10 months of observation, the patient's course appears to have stabilized. Although
unable to work, he is ambulatory and free of
edema.
Discussion
Three of the various obstructive phenomena
Rest
91
39
7.41
24
1965
Exercise
89
39
7.41
24
40
15
associated with fibrous mediastinitis are demonstrated in this case: that in the superior
vena cava, the tracheobronchial tree, and the
pulmonary veins. Aside from the cosmetic effects, superior vena caval obstruction produced no untoward physiological disturbance.
A bronchogram in 1962 showed partial
obstruction of the left lower lobe bronchi with
some distal atelectasis. Pulmonary function
studies are compatible with moderately severe,
nonreversible obstructive disease. In particular, the high inspiratory resistance and nonelastic work of breathing are suggestive of fixed
airway obstruction which would result from
Figure 5
Lung parenchyma showing marked thickening of the pleura and interlobular septa by edematous, fibrous, vascular connective tissue. The interalveolar septa are thickened; some alveoli
are collapsed; others are distended.
Circulation, Volume XXXIII, June 1966
BOTTICELLI ET AL.
868
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Figure 6
Small branch of the pulmonary artery showing marked concentric proliferation of cells. The
adjacent alveoli are lined by culboidal epithelium of respiratory ducts, and the spaces are
filled with large mononuclear cells.
bronchial compression. Marked abnormality of
ventilation-distribution was demonstrated by
the decrease in dynamic compliance with
increasing respiratory frequency. The low
static compliance noted in 1965 was compatible with pulmonary fibrosis and resulted in an
increase in the elastic work of breathing.
Three possible causes of pulmonary hypertension in chronic adhesive mediastinitis may
be considered. Local pulIoMary artery obstruction, functionally resembling coarctation,
has been described in a few cases."' 12
The absence of a characteristic murmur and
the lack of obstruction of major pulmonary
arteries on angiography is strong evidence
against this possibility. Furthemore, the microscopic appearance of the distal pulmonary
vessels in the lung biopsy show the marked
medial hypertrophy associated with pulmonary arteriolar hypertension.18
Data from the cardiovascular study suggest
that pulmonary hypertension was due to pulmonary venous obstruction since marked elevation of the pulmonary artery wedge pressure
was noted. The postcapillary location of
vascular obstruction implied by elevation of
the "pulmonary-capillary" pressure was confirmed by retrograde pulmonary venous catheterization at the time of surgery. The pulmonary artery wedge pressure is usually normal
in cases of pulmonary hypertension due to
pulmonary fibrosis.'9 The normal left atrial
and ventricular pressures clearly rule out left
heart disease as the cause of pulmonary hypertension and indicate a locus of resistance
estimated at nearly 50% of the total pulmonary
resistance in the postcapillary segments of the
lesser circulation. The rise in pulmonary
artery and wedge pressures with exercise further supports the interpretation of a fixed
pulmonary venous resistance.
The findings in this case provide an explanation for the hemoptysis which is a frequent accompaniment of pulmonary venous
hypertension when due to mitral stenosis
or cor triatriatum20, 21 or adhesive mediasti" In addition, the symptoms of left
nitis.' '1
heart failure and the pleural transudate can
Circulation. Volume XXXIII, June 1966
FIBROUS MEDIASTINITIS
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be related to the pulmonary venous and consequent pulmonary capillary hypertension.
The markedly delayed washout of indicator
following segmental pulmonary arterial injection probably reflects decreased flow in the
segments receiving most of the injectate. This
may be due to partial atelectasis in the case
of the left lower lobe, but more likely reflects
variations in the degree of pulmonary venous
obstruction in various segments with consequent uneven flow distribution. Hurwitz and
associates22 have studied the venous collateral
circulation in dogs following pulmonary venous ligation and have shown that collateral
veins drain into the azygos system via pleural
adhesions and return blood to the right heart.
This collateral system is capable of carrying
up to 20% of the flow of an unobstructed
lung. A significant shunt (left-to-right) is ruled
out in this case by the normal contour of the
indicator-dilution studies following inferior
caval and proximal pulmonary arterial injection.
The vascular changes in the pulmonary arterioles closely resemble those reported in mitral
stenosis and other forms of secondary pulmonary hypertension. These so-called "protective" lesions have been described in pulmonary lobes with pulmonary venous
obstruction while those areas without venous
obstruction are spared.3 1 23
Andrews23 has suggested that interstitial
fibrosis is the result of complete, partial, or
intermittent pulmonary venous obstruction.
His evidence is not convincing, however, since
two of his five patients had left atrial enlargement without definite pulmonary venous obstruction, two had mediastinal fibrosis and
the fifth had several congenital defects
in addition to left pulmonary venous stenosis.
Additional reports of congenital pulmonary
venous stenosis24-26 have described pulmonary
fibrosis, and Stovin and Mitchinson27 have
reported a case of pulmonary fibrosis with
obstruction of intrapulmonary veins. The rarity
of extensive pulmonary fibrosis in mitral
stenosis, most cases of atrial thrombosis, atrial
myxoma, cor triatriatum, and chronic severe
left heart failure suggest that pulmonary
Circulation, Volume XXXIII, June 1966
869
fibrosis may not be causally related to pulmonary venous hypertension in man. Reports
of animal experiments28-30 in which pulmonary
fibrosis followed acute pulmonary venous
ligation have doubtful application since acute
hemorrhage and infection invariably follow
acute ligation. A common etiology for pulmonary and mediastinal fibrosis is a more
attractive hypothesis.
A common infectious cause for the pulmonary fibrosis and mediastinitis may exist
in our case. Histoplasmosis has been frequently
implicated in the past decade9 31-33 and is
suggested by the 4+reaction to skin-testing
in this patient. Despite the negative complement-fixation studies, negative histological
examination, and negative fungus culture, histoplasmosis may be present.34 36 On the other
hand, a positive skin test alone is inconclusive
evidence. Other etiological agents which have
been reported, such as tuberculosis, syphilis,
and actinomycosis were eliminated from consideration by history and appropriate studies.
Hawk and Hazard35 pointed out the gross
and histological similarity of fibrous mediastinitis, fibrosing retroperitonitis, and Riedel's
struma. These conditions may represent variable manifestations of a tissue response to
one or more undetermined factors.
Summary
A patient with chronic fibrous mediastinitis
presented with bronchial, superior vena caval,
and pulmonary venous obstruction, pulmonary
hypertension, and pulmonary fibrosis. Pulmonary venous obstruction was confirmed at
surgery and explains the hemodynamic findings of elevated pulmonary artery and pulmonary wedge pressures despite low left atrial
pressure. Pulmonary function studies showed
marked alterations in ventilation-distribution,
diffusion, work of breathing, and fixed airway
resistance.
It is concluded that the pulmonary arterial
hypertension was due, in large part, to the
pulmonary venous hypertension caused by
pulmonary venous obstruction. Unsuccessful
surgical intervention has been followed by 10
BOTTICELLI ET AL.
870
months of observation during which aldosterone inhibition together with use of chlorothiazide has prevented recurrence of heart failure
and pleural effusion.
The relationship between the physiological
abnormalities and the patient's symptoms is
discussed along with the possible relationship
between pulmonary venous obstruction and
pulmonary fibrosis.
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Acknowledgments
indebted to Dr. Paul Kimmelstiel,
authors
are
The
Research Professor of Pathology, Marquette University School of Medicine, for review of the histological
sections, and Dr. Dudley Johnson, Resident in Cardiovascular Surgery, for his cooperation in obtaining
data at surgery.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
1 1.
12.
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An Intellectual Exercise and Challenge to Contemporary Writing
The scientific paper is a fraud in the sense that it does give a totally misleading narrative of the processes of thought that go into the making of scientific discoveries. The
inductive format of the scientific paper should be discarded. The discussion which in
the traditional scientific paper goes last should surely come at the beginning. The scientific facts and scientific acts should follow the discussion, and scientists should not be
ashamed to admit, as many of them apparently are ashamed to admit, that hypotheses
appear in their minds along uncharted by-ways of thought; that they are imaginative
and inspirational in character; that they are indeed adventures of the mind.-P. B.
MEDAWAR: Is the Scientific Paper Fraudulent? Yes; It Misrepresents Scientific Thought.
Saturday Review, p. 43 (Aug. 1), 1984.
Circulation, Volume XXXIII, June 1966
Pulmonary Venous and Arterial Hypertension due to Chronic Fibrous
Mediastinitis: Hemodynamics and Pulmonary Function
JAMES T. BOTTICELLI, DONALD P. SCHLUETER and RAMON L. LANGE
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Circulation. 1966;33:862-871
doi: 10.1161/01.CIR.33.6.862
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1966 American Heart Association, Inc. All rights reserved.
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