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47. Hanrwon, W. and Lunow, A. A. Gas exchange in
lung deprived of pulmonary arterial supply.
Yale J. Biol. & Med., 22: 251, 1960.

48. Houx, V. N. and Moser, K. M. Unpublished data.

49. Nexson, J. R. and Smita, J. R. The pathologic
physiology of pulmonary embolism. A physiologic
discussion of the vascular reactions following
pulmonary arterial obstruction by emboli of
various sizes. Am. Heart J., 58: 916, 1959.

50, Rosster, P. H., BuHtmann, A. A. and Wirsincer, K.
Respiration. Edited and translated by Luchs-

Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

inger, P. C. and Moser, K. M. St. Louis, Mo.,
1960: C. V. Mosby Co.

51. Dovt, J. T., Witson, J. S. and Warren, J. V. The
pulmonary vascular response to short term
hypoxia in human subjects. Circulation, 5: 263,
1952.

52. Duxe, H. N. Observatién on effects of hypoxia on
pulmonary vascular bed. J. Physiol., 135: 45, 1957.

53, Rivera-Estrapa, C., Sattzman, P. W., Sivcer, D.
and Karz, L. N. Action of hypoxia on pulmonary
vasculature. Circulation, 6: 10, 1958.

AMERIGAN JOURNAL OF MEDICINE

PO 882-973


Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al. 273

: ,

Fic. 3. Cineangiogram frames, A, poor filling of middle and lower lobes of right

lung. B, poor filling of upper lobe of left lung in posteroanterior projection.

G, oblique projection.

Surgical exploration was planned with cardio-
pulmonary bypass standby. It was believed from
available evidence that, since the major portion of the
right pulmonary flow was already obstructed, the
patient might tolerate complete occlusion of the right
main pulmonary artery, permitting open thromb-
endarterectomy without bypass. If relief of the right
pulmonary artery obstruction were achieved, the left
pulmonary artery then could be occluded, and repair
of obstructions to the left upper lobar branch accom-
plished. Cardiopulmonary bypass could have been
instituted promptly with a minimum of risk and
manipulation.

A bilateral anterior thoracotomy was performed in

vou. 35, aucusr 1963

the right fourth and left third interspaces with sternal
transection. Excellent surgical exposure of the lungs
and pulmonary arteries was afforded by this approach.
Vascular fibrous pleural symphysis was present over
the entire middle and lower lobes of the right lung
and over the apical posterior segment of the left lung,
The areas of involvement were further evident by
difficulty in maintaining a clean plane when dissect-
ing the adventitia of the large apical posterior pulmo-
nary artery branch on the left and upper and middle
lobe branches on the right. Palpation disclosed
marked fibrous thickening in these vessels and
strongly suggested complete occlusion.

The main pulmonary artery measured 3.5 to 4 cm.



278

cyanosis may be present if the cardiac output is
severely reduced. The chest may expand well
and may be normal to percussion and ausculta-
tion, as in the patient described herein.

Cardiac examination, however, is often more
revealing. A variety of murmurs has been
described whose unusual transmission and
timing may suggest an extracardiac origin
[20,22]. Most commonly noted has been a high-
pitched systolic murmur in the pulmonic
region [38,43], although occasionally a systolic
murmur at the apex has been reported. Dias-
tolic, “‘to-and-fro” and continuous murmurs
have also been described [22,43]. It is probable
that these murmurs arise from the turbulence
created in a large vessel by flow past a partial
obstruction. We have scen three patients with
high-pitched systolic murmurs in the pulmonic
area which appeared to extend through the
second sound (an observation confirmed in one
case by phonocardiography) and which became
louder with inspiration. One patient was the
subject of this report. The two other patients had
evidence suggesting pulmonary embolism in-
volving the upper lobe of the left lung. Such a
murmur, therefore, may have diagnostic value.
In reviewing the reported series, it appears that
the discovery of a systolic murmur with some
atypical features—in the absence of primary
cardiac disease—should suggest the possibility
of pulmonary vascular occlusive disease. How-
ever, the absence of murmurs does not exclude
the diagnosis [7,43].

The presence of an accentuated pulmonic
component of the second sound is the usual
finding in patients with extensive embolic
obstruction. However, it has been stated that a
normal pulmonary component may occur in
such patients and, when it does, suggests
obstruction of the pulmonary artery near the
pulmonary valve rather than in more distal
portions of the vascular tree [7].

As full-blown cor pulmonale appears, of
course, the characteristic physical findings
associated with right ventricular failure—
hepatomegaly, ascites and peripheral edema—
make their appearance.

Evidence of recent or remote peripheral
venous disease is the exception rather than the
rule in such patients. This indicates that either
the original venous embolic source was not in
the extremities or that the embolic source has
resolved before the patient’s problem reached
clinical detection. The frequency of mural

Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

thrombi in the right side of the heart as an
embolic foci in patients with emphysema and
cor pulmonale has recently been emphasized
by Baum and Fisher [42].

Laboratory Studies. The white blood cell count
and hematocrit are usually within normal limits
[2]. Polycythemia is not encountered with massive
pulmonary artery occlusion per se but when
present is a consequence of associated cardio-
pulmonary disease.

The chest roentgenogram so often reveals no
abnormalities that this does not exclude the
diagnosis [25,43,44]. Marked enlargement of the
pulmonary arterial shadows, particularly uni-
lateral enlargement, is suggestive. Zones of
radiolucency in the lung fields associated with
zones of increased vascularity elsewhere (as in
our patient) may provide a’ clue. Evidence of
old pleural disease and/or fibrotic linear
parenchymal residuals compatible with prior
infarction may be helpful. Of special value may
be the fluoroscopic observation of absent or
diminished hilar pulsations in a patient with a
prominent pulmonary conus or other evidence
of right ventricular overload.

The electrocardiogram is of little differential
value. With long-standing cor pulmonale, the
electrocardiogram shows the changes expected,
indicating right ventricular dilatation and
hypertrophy. Often, as in our patient, the
electrocardiogram is normal because the process
has not been of sufficient duration to have
induced significant alteration in the right
ventricle or atrium.

Since the routine studies, as described,
rarely provide a definitive answer, cardiac
catheterization, pulmonary angiography and
detailed measurements of the arterial blood
gases are usually necessary to confirm the
diagnosis. Although the first two procedures are
not without risk in patients with pulmonary
vascular compromise, one must have definitive
data if a decision regarding a procedure such as
pulmonary endarterectomy/embolectomy is re-
quired. However, before proceeding to catheter-
ization and angiography, arterial blood gas
studies may be used to provide supportive
evidence for the diagnosis of extensive embolic
occlusion.

Perhaps the simplest screening test is the
measurement of the end tidal-arterial carbon
dioxide gradient [45,46], This test is based on
the concept that embolic occlusion produces a
zone of ventilation without perfusion. Therefore,

AMERIGAN JOURNAL OF MEDICINE


Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

TABLE IV
VENTILATORY STUDIES

Per
cent

Pre-
Study Actual | Pe | of
Values | dicted | Pre
ues | dicted
Values
Postoperative®
‘Tidal air volume (cc.) 1,094 oe
Vital capacity (cc. 3,073 |3,946 | 78
‘Timed vital ca
1 second 36 | >85
2 seconds. 96 | >90
3 seconds. too | 100 | ...
‘Maximum breathing capacity (L./min. 90 | 116 | 78
Functional residual capacity (cc.). 2919 | we fans
Residual volume (cc. 873 | oo. | ee
‘Total lung capacity (cc.). 4,47 |5,818 | “83

Ratio of residual volume to total lung
‘capacity (%) +--+
Per cent Ne after 7 minutes.

2

Convalescent

‘Tidal air volume (cc.)

Vital capacity (cc.).

‘Timed vital capacity (%)
cond. :

iat

105

* December 13, 1961, six weeks after operation,
‘May 9, 1962, six months after operation,

normal. Ventilatory studies (Table 1v) yielded
normal results, and the chest roentgenogram (Fig.
2C) was unchanged from that obtained in mid
December. The end tidal-alveolar arterial blood
carbon dioxide tension gradient was 7 mm. Hg. The
patient has progressively improved following surgery.
At present, he is fully active and does not experience

275

dyspnea. The pulmonary component to the second
heart sound is no longer accentuated, the pulmonary
systolic murmur is absent, and the splitting of the
second heart sound is normal. His exercise tolerance
is similar to that which he enjoyed two years previously.

COMMENTS

In the past, extensive thrombotic occlusion of
the pulmonary arterial system attracted interest
primarily as an unusual postmortem finding in
patients who succumbed to chronic cor pul-
monale. However, with the advent of surgical
technics which have made pulmonary embolec-
tomy and endarterectomy feasible, “thrombotic”
cor pulmonale must now be added to the
important list of potentially curable forms of
heart disease. Indeed, it is now possible to
diagnose chronic massive thrombosis of the
pulmonary arteries prior to the development of
clinically detectable heart disease. Diagnostic
and surgical advances thus have imposed upon
the physician a demand for increased alertness
and accuracy in the detection of pulmonary
embolic obstruction—a demand which must be
met if “therapeutic availability” is to be
translated ‘into “therapeutic application.” Iden-
tification of patients with this disorder requires
familiarity with those situations in which it is
most likely to occur, the clinical features asso-
ciated with it and the laboratory studies which
can be called upon to confirm the diagnosis.

Incidence, It is almost axiomatic that height-
ened interest in a given disease leads to an
increased incidence of discovery. Therefore,
current opinions regarding the rarity of exten-
sive pulmonary thromboembolism may well be
revised in the future, and available estimates of
its incidence should be viewed in this light. Ring

TaBLe v*
BLOOD GAS STUDIES SIX MONTHS AFTER OPERATION
01% | PAQ: | PaO, Aca _| pCO:

Data Minute | yan'Siyke | (mm. He) | (mm. Hg) | (nm. Hg) | (am. Hg)| PH
Atrest..cccceeeeeceeeeeeeeeeeeaee 97 104 99 5 39 | 7.42
During exercise........ss0seeeeees 5 95 108 89 19 36 | 7.44

10 95 108 88 20 36 «| 7.44
After exercise... beeeees 10 98 105 100 5 38 | 7.43
During inhalation of 32% oxygen....| 10 100 181 40 (| 7.40

Nore: End tidal-arterial carbon dioxide tension difference at rest was 7 mm. Hg. Exercise level same. asin Table 1.

vou. 35, aucust 1963



274

in diameter and was tense. No palpable disease was
noted therein.

Complete occlusion of the right pulmonary artery
produced a palpable increase in pulmonary artery
pressure on the left and a bigeminal cardiac rhythm
which continued throughout the twenty-five minute
period necessary to complete the endarterectomy.
Careful dissection within the right pulmonary artery
freed an adherent, organized thrombus which had its
origin in the most distal portion of the right pulmo-
nary artery and extended into one of the upper, the
middle and the lower lobe branches. The specimen
(Fig. 4) measured 5 cm. in length. The staghorn
appearance was as expected from the cineangiograms.
Occlusion of the left pulmonary artery was then
easily tolerated, and fifteen minutes were required to
dissect free a complete occlusion of the first branch
(apical posterior) of the pulmonary artery to the
upper lobe of the left lung. Since the patient was
being maintained on heparin therapy, meticulous
surgical hemostasis was necessary. At the completion
of the surgical procedure, a tracheostomy was per-
formed to improve tracheobronchial cleansing and
assist respiration if such proved necessary.

Heparin anticoagulation, prophylactic penicillin
and streptomycin, and digitalis therapy were con-
tinued after the operation. Convalescence was smooth
with minimal drainage from the chest; the tubes were
removed on the fourth day after operation.

Clinical improvement was noted by the patient
in the early period after operation and was confirmed
by various physiologic measurements.

Despite the restrictive ventilatory effects of surgery
and mild associated alveolar hypoventilation twenty-
four hours after the surgical procedure, the end-
alveolar arterial blood carbon dioxide tension
gradient was recorded as 15 mm. Hg—a significant
reduction from the value of 27 mm. Hg before the
operation. .

In mid December (six weeks after the operation),
arterial blood gas studies and ventilatory studies were

Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

Fic. 4, Thrombotic cast of distal right pulmonary artery

and branches plus fragments of this thrombus and that
from upper lobe branch of left pulmonary artery.

obtained. (Tables m and 1v.) At that time the end
tidal-arterial blood carbon dioxide gradient was
12 mm. Hg. There was still a moderate restrictive
ventilatory defect present; this was due no doubt to
the effects of the bilateral thoracotomy. Chest
roentgenograms during this admission (Fig. 2B)
showed marked reduction in the size of the pulmonary
artery shadows.

The patient was readmitted six months after sur-
gery for restudy. Cardiac catherization was attempted.
However, no suitable vein could be found in the
upper extremities for introduction of the catheter. It
was not considered justified to catheterize the right
side of the heart via the inferior vena cava since it was
thought that this vessel had been involved at the time
of the original thrombophlebitis. Although it was
disappointing not to have hemodynamic data, the
repeated blood gas studies (Table v) indicated that
the patient’s alveolar gas exchange had returned to

Taste u1*
BLOOD GAS STUDIES SIX WEEKS AFTER OPERATION

, 02% | PAO: | PaO: Aca pCO:
Data Minute | Van Slyke | (mm. Hg) | (mm. Hg) | (mm. Hg) | (mm. Hg)| PH
95 107 5 32 38 | 7.40
5 93 103 69 ‘34 a |7.38
10 94 105 B 32 39 «7.37
10 96 115 82 33 31 | 7.40
During inhalation of 32% oxygen....| 10 101 199 113 be 29 «17.44

Nore: End tidal-arterial carbon dioxide tension difference at rest was 12. mm. ‘Hg. Exercise level same as in Table n.

AMERIGAN JOURNAL OF MEDICINE


Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

Mitral stenosis was present in six of twenty-three
cases in one series [7] and in nineteen of eighty-
eight cases in another (30]. More recently, the
percentage of patients with mitral stenosis in
whom extensive thrombotic occlusion develops
appears to be on the decline [70,22].

The available data, therefore, indicate that
cor pulmonale due to thrombotic occlusion of
major pulmonary arteries is most frequent in
those situations in which the diagnosis is easily
obscured by the presence of known cardiac or
pulmonary disease. The symptoms of occlusion
often have been dismissed as compatible with
“deterioration” of function due to the coexisting
disorder. It is likely that attention to un-
explained “deterioration,” especially in the
form of cor pulmonale, may lead to discovery of
additional cases amenable to surgical correction.

Symptoms. Chronic pulmonary thromboem-
bolism has been described in patients ranging
in age from fifteen months to eighty-nine years.
However, the disorder is most common in
patients beyond the age of forty in whom the
incidence of all forms of thromboembolism is
highest. As mentioned previously, antecedent
cardiac or pulmonary disease is commonly
present. There is no sex difference.

Dyspnea is by far the most commonly reported
complaint [7, 10,20,23,30,38,39]. This dyspnea is
frequently out of proportion to that expected on
the basis of collateral evidence of cardiopulmo-
nary disease. This disparity between “dyspnea
expected” and “dyspnea observed” is animpor-
tant diagnostic clue in patients with massive
thrombosis. The dyspnea is also rather char-
acteristic in its lack of response to treatment.
Indeed, unremitting progression despite vigor-
ous therapy is often noted.

Hemoptysis and pleuritic chest pain have
been frequently noted by previous investigators.
Carroll [20] reported such a history in four of
five cases and Ball et al. [7] in fourteen of
twenty-three cases. Both of these symptoms
often have been attributed to recurrent pneu-
monitis associated with underlying pulmonary
disease during life and recognized as manifesta-
tions of embolism only retrospectively. These
symptoms of repeated pulmonary infarction in
patients with massive occlusive thrombi proba-
bly reflect periodic release of clot fragments of
the primary thrombus to more distal pulmonary
arterial branches [77]. Recurrent episodes of
fever and cough, usually attributed to “pneumo-
nitis,” may provide an important historic clue,

vou. 35, aucust 1963

277

especially if associated with dyspnea, hemoptysis
and/or chest pain.

Severe substernal and epigastric pain also
have been described in a number of patients.
The mechanism of the former is poorly under-
stood and has been attributed by some to a vagal
reflex [33], by others to a decreased coronary
flow caused by right ventricular dilatation and
increased coronary venous pressure [39], and by
still others to dilatation of the pulmonary artery
with compression of the right coronary artery
at its origin. Epigastric pain most commonly
has been associated with hepatic congestion
after the development of right ventricular
failure, but has been encountered in some
patients well in advance of this event.

Worthy of special mention are the symptoms
suggestive of central nervous system disease
which have been noted in a number of patients
with extensive pulmonary thrombotic occlusion.
Syncopal attacks, often recurrent [7, 10,22),
blurred vision [39] and varying degrees of
mental confusion [7,70,22,30,40,47] have all been
described with some frequency. These symptoms
may have multiple etiologies including marked,
venous hypertension with cerebral edema,
severe reduction in cardiac output with cerebral
ischemia, “reflexes” initiated by embolism per se
and, rarely, terminal carbon dioxide intoxica-
tion [40,47]. Recurrent paralysis of the left
laryngeal nerve due to pressure from a distended
left pulmonary artery has also been reported
[70].

Although the symptoms of extensive pulmo-
nary thrombosis are numerous, it is important
to emphasize that they can easily be attributed
to the underlying cardiac or pulmonary disease
per se. It is essential to recognize that the
symptoms of massive occlusion are more fre-
quently insidious than dramatic. If sudden,
dramatic onset or progression of symptoms is
required before the diagnosis is entertained,
many cases will be overlooked [42].

Physical Signs. Like the historic features, the
physical signs encountered in chronic massive
occlusion are far from uniform. They are deter-
mined by the location, extent and duration of
the thrombotic process, as well as by the
presence of other cardiopulmonary disease.

In the absence of primary lung disease,
physical examination in’ such patients may be
surprisingly unrewarding despite a history of
severe dyspnea. Clubbing of the digits and
cyanosis are usually absent, although peripheral



Reprinted from
The AMERICAN JOURNAL OF MEDICINE
v.35 #2 August 1963

Chronic Thrombotic Obstruction of Major
Pulmonary Arteries"

Report of a Case Successfully Treated by Thrombendarterectomy, and a
Review of the Literature

Lr. Cupr. Vernon N. Houx, mc, usn, CHartes A. HuFNAGEL, M.D.,

Bethesda, Maryland

Washington, D. C.

Cmpr. James E. McCLenaTHAN, MC, usN and KennetH M. Moser, M.D.

Bethesda, Maryland

XTENsIvVE pulmonary thromboembolism is
E usually regarded as a sudden, dramatic
event accompanied by acute symptoms and an
appreciable immediate mortality. Less widely
recognized is the type of pulmonary thrombo-
embolic disease which is relatively silent and
clinically evident in the form of pulmonary
insufficiency and chronic cor pulmonale due to
marked reduction in the pulmonary vascular
bed area [7-5]. Recent improvements in surgical
capabilities have made discovery of patients
with “thrombotic cor pulmonale” of consider-
able importance since this form of cor pulmonale
is now, at least, potentially curable.

Most of the literature dealing with surgical
intervention in patients with extensive pulmo-
nary embolism has dealt with the feasibility of
immediate embolectomy in the face of acute,
massive occlusion of the pulmonary artery or its
major branches. In 1908 Trendelenberg [5]
first attempted this then daring procedure on a
patient who was at the point of death, uncon-
scious and without pulse so that no anesthesia
was required. Since this pioneer effort, there
have been multiple reports of attempted
emergency embolectomy, with several instances
of success [6-74]. Recently, the use of emergency
cardiopulmonary bypass has extended the
serious limitations of time imposed by massive
occlusion, thus enhancing the feasibility and
success of surgical intervention [75].

Washington, D.C.

The emphasis on detection and therapy of
acute massive pulmonary vascular obstruction is
understandable, since chronic obstruction of
major pulmonary arteries is less dramatic, less
frequently encountered and even less frequently.
diagnosed during life. Furthermore, despite a
history of embolic episodes preceding the
appearance of cor pulmonale, therapeutic
enthusiasm has often been dampened by the
assumption that the occlusive disease involves
multiple small peripheral branches and, there-
fore, is not subject to correction, and the
acknowledged increased risk of cardiac catheter-
ization and angiographic study of patients with
compromise of the pulmonary vascular bed.
Nevertheless, extensive pulmonary thrombi
constitute such a major threat to the patient in
terms of both morbidity [76-19] and mortality
that this potentially curable entity must be ruled
out in patients who present with the suggestive
signs and symptoms to be recounted here.

A search of the literature has revealed
approximately 250 reported cases. of chronic
thromboembolic obstruction of the major pul-
monary arteries. In only six. of these was the
diagnosis established before death [7,70,20,27],
and in only three was direct surgical therapy
attempted. In the first of these three, the patient
underwent an exploratory operation in 1950, at
which time the left pulmonary artery was found
to be small with minimal pulsations [20]. No

* From the Departments of Medicine and Surgery, U.S. Naval Hospital, Bethesda, Maryland, and the George-
town University Medical School, Washington, D.C. and The Pulmonary Section, Georgetown Clinical Research
Institue, Aviation Medical Service, Federal Aviation Agency, Washington, D.C. The opinions expressed are those of the
authors and do not necessarily reflect the opinions of the Navy Department. Manuscript received July 25, 1962.

vox. 35, aucusT 1963

269



280

cineangiography which permits detailed ob-
servation of a specific vascular bed area using
small amounts of contrast medium. Large
injections of contrast medium should be avoided
in the interests of safety. Repeated small injec-
tions via a catheter in the pulmonary artery or,
if this is not possible, in the right atrium or
ventricle, provide data which should be defini-
tive in patients with occlusion of major pulmo-
nary arterial branches.

Operative Approach, Certain features of the
operative approach in patients with massive
occlusion are worthy of mention. Although
unilateral occlusion may be employed success-
fully, as in the case reported herein, cardio-
pulmonary bypass has certain advantages:
further overload of the right ventricle during
occlusion is avoided; the pulmonary vascular
tree can be examined in detail; and the surgical
procedure itself can be accomplished in more
leisurely fashion. The disadvantages of bypass
(e.g., bleeding tendency after operation, neces-
sity for multiple cannulations) must be balanced
against these advantages.

Inspection—and even palpation—of the major
pulmonary arterial branches is not always
reliable in confirming the presence of a throm-
bus, particularly when soft thrombus or a
thrombus which partially occludes a vessel is
being dealt with. Thus, with angiographic
evidence of occlusion, arteriotomy should not be
abandoned when palpation of the involved
vessels fails to disclose a firm intravascular mass.

In patients severely disabled by their disease,
in whom surgery has not been feasible in the
past, the suggestion of Cooley and Beall [75]
that bypass be instituted using a portable
apparatus and peripheral vessels seems worthy
of mention. This procedure might also be used
in patients who would be benefited. by the
procedure but might otherwise be unable to
withstand the operation.

The need for anticoagulant therapy with
heparin before and after surgery should be
stressed also. In patients suspected of this dis-
order, heparin therapy should be utilized to
forestall further thrombotic or embolic disease
during the diagnostic period. Preservation of
vascular patency after surgery is obviously
critical, and heparin therapy is strongly advised,
especially if endarterectomy is required. Now
that high potency, low toxicity fibrinolytic
agents are available, it is possible that these
agents may be uéed in an effort to restore

Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

vascular patency in those patients in whom the
diagnosis is made promptly. They are also
worthy of trial when operative facilities for
definitive surgery are not available and when
evidence of rethrombosis appears in the period
after operation.

CONCLUSIONS

Our discussion has indicated that the path
leading to the diagnosis of treatable forms of
massive pulmonary embolic occlusion is a
difficult one to follow. Obviously, the diagnosis
is much more easily made in the patient without
coexisting pulmonary or cardiac disease. Yet,
despite the diagnostic difficulties involved, the
possibility of embolic occlusion should not be
abandoned in the face of other cardiopulmo-
nary disorders, for its incidence is greatest in
such patients. Discovery of extensive occlusion
may transform an apparent “end-stage” patient
into a treatable one. Even the demonstration
that multiple small peripheral emboli exist is
not without benefit; for, even though surgery is
not feasible in such patients, such data may lead
to re-evaluation of the need for anticoagulant
therapy in patients with chronic cardiopulmo-
nary disease.

It seems likely that heightened awareness of
the possibility of remediable massive occlusion,
plus the increasing availability of sophisticated
diagnostic and surgical technics, will lead to the
report of many similar cases in which this
disorder is treated successfully in the future.

SUMMARY

A case is reported of chronic massive thrombo-
embolic occlusion of major pulmonary arterial
branches successfully treated with embolectomy
and endarterectomy. The historic features,
physical signs and pathophysiologic alterations
which form the basis for the diagnosis of this
disorder are reviewed.

REFERENCES

1, Batt, K. P., Goopwm, J. K. and Harrison, C. V.
Massive thrombotic occlusion of large pulmonary
arteries. Circulation, 14: 766, 1956.

2. Harvey, R. M. and Ferrer, M. I. A clinical con-
sideration of cor pulmonale. Circulation, 21: 236,
1960.

3. Peau, C. P. Cor pulmonale from recurrent pulmo-
nary emboli. Lancet, 1: 345, 1951.

4. Hargis, P. and Hears, D. The Human Pulmonary
Circulation, p. 318. Baltimore, 1962. Williams &
Wilkins Co.

5. TRENDELENZERG, F. Ueber die Operative Behand-

AMERIGAN JOURNAL OF MEDICINE


Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

the end tidal (“mean alveolar’) carbon dioxide
tension falls below the directly measured arterial
carbon dioxide tension by an amount propor-
tional to the area blockaded. Although the
development of infarction, the presence of
associated pulmonary disease and other factors
[45,47] limit the utility of this procedure, it
would seem to have its greatest value in the
patients under discussion herein—those with
massive embolic occlusion. The end tidal-
arterial carbon dioxide gradient in the case
reported herein was definitely abnormal and
diagnostically helpful. This patient’s gradient
of 27 mm. Hg before operation was well above
the value of 17.2 mm. Hg observed in the most
severely emphysematous patient (residual vol-
ume/total lung capacity = 67 per cent) yet
studied in our laboratory [50].

Measurement of lung volumes is of value only in
excluding the presence of associated obstructive
or restrictive ventilatory defects. Demonstration
of normal lung volumes is helpful in ruling out
other disorders which may produce dyspnea.

Measurement of the arterial blood gases at rest,
during exercise and during the breathing of
oxygen-rich mixtures is of greater value than
lung volume determinations. The physiologic
abnormalities induced by extensive pulmonary
embolization have been reviewed in detail by
Parker and Smith [26] and by Nelson and Smith
[49]. These investigators have pointed out that
the pulmonary vascular reserve is so vast that
occlusion of 60 to 70 per cent of the vascular
bed is required before pulmonary hypertension
appears with the subject at rest. However, study
of arterial blood gases, particularly during
exercise, may reveal occlusions of lesser degree.
Arterial .blood gas values with the patient at
rest are usually within normal limits, although
the carbon dioxide pressure may be slightly
reduced due to alveolar hyperventilation. Dur-
ing exercise, however, the increase in pulmonary
blood flow may be associated with a widening
of the alveoloarterial oxygen tension gradient
characteristic of a diffusion insufficiency. This
widening of the oxygen tension gradient reflects
critical reduction of the alveolocapillary area
available for gaseous exchange [2,48]. The high
diffusibility of carbon dioxide and the char-
acteristics of the carbon dioxide dissociation
curve prevent the appearance of significant
elevation in arterial carbon dioxide tension
under these circumstances. In truly massive
occlusion, an abnormal A-a ‘oxygen gradient

von. 35, aucusT 1963

279

may be present at rest with normal pulmonary
blood flow, and this gradient widens further
with exercise. Inhalation of oxygen-rich mix-
tures serves to differentiate shunt from diffusion
insufficiency, since normal oxygen saturation is
achieved in diffusion defects but not when a
significant shunt is present. The type of diffusion
abnormality encountered in extensive embolic
occlusion is similar to that seen following
pneumonectomy, i.e., it is due to a critical loss
of available diffusing surface rather than a
thickened alveolocapillary membrane.

Right heart catheterization is a valuable pro-
cedure in establishing the diagnosis of embolic
occlusion. The presence of congenital cardiac
defects which might be associated with pulmo-
nary vascular obliteration can be excluded. In
the absence of such defects, the characteristic
abnormalities of “primary pulmonary hyper-
tension” are discovered. Assumirig that the
pulmonary artery and “wedge” can be entered,
catheterization with the subject at rest will
disclose a normal wedge pressure but mild to
moderate pulmonary hypertension which is
sharply accentuated during exercise. In patients
with less extensive occlusion, exercise during
catheterization becomes critical since normal
pulmonary arterial pressures may be present at
rest. With exercise, however, progressive eleva-
tion in pulmonary arterial pressure will be noted
as the pulmonary bed becomes a “fixed resist-
ance” system in which increased flow is attained
only with an increase in pressure. The level of
flow at which hypertension appears is a function
of the degree of vascular depletion although
associated hypoxemia may increase the degree
of pulmonary hypertension [57-53].

Unfortunately, all the studies mentioned thus
far may not yield a diagnosis. In those instances
in which congenital cardiac disease or significant
lung disease exists, the data obtained may be
compatible with these disorders and the possible
contribution of embolic occlusion uncertain.
Furthermore, occlusion of a major pulmonary
arterial branch—even total unilateral occlusion
—may be difficult to detect by cardiac catheter-
jzation and arterial blood studies if the un-
obstructed lung is normal. Finally, even though
the diagnosis is strongly suggested by prior
studies, localization of the occlusion(s) is vital
in determining the feasibility and technic of
surgical attack. Such localization is possible
only by angiocardiography. In carrying out this
procedure, the preferred method is selective



276

and Bakke [23] found twenty-one cases of
massive pulmonary arterial occlusion in 11,511
autopsies carried out between 1935 and 1954, an
incidence of 0.18 per cent. Billings [24], in an
extensive review, reported an ‘incidence in
various autopsy series ranging from 0.2 to
0.7 per cent.

Such reports indicate that major thrombotic
occlusion of the pulmonary vascular bed occurs
with sufficient frequency to merit consideration
in any patient with apparent “primary pulmo-
nary hypertension.” It has been demonstrated
that thromboembolism constitutes the most
frequent cause of pulmonary vascular obstruc-
tion [25] and that primary disease of the pulmo-
nary vessels is rare [70]. Indeed, there is a
growing body of evidence which suggests that
a significant percentage of patients with
“primary pulmonary hypertension” actually
represent instances in which prior widespread
pulmonary embolism and thrombosis has par-
tially resolved, leaving in its wake histologic
evidence suggesting primary vascular disease
[70,26].

Although pulmonary embolic disease as a
“pure” cause of cor pulmonale—as in the case
reported herein—appears rather uncommon
[2], thromboembolism as a major contributory
cause to cor pulmonale in subjects with pre-
existing cardiac or pulmonary disease is un-
doubtedly more frequent than is currently
suspected. Pulmonary embolism is most com-
mon beyond the third decade [26], when latent
and overt cardiopulmonary disease is also more
frequent. The higher incidence of pulmonary
embolism and infarction in patients with known
cardiopulmonary disease is widely appreciated.
Therefore, it is cogent to suggest that pulmonary
vascular occlusion be considered in patients
with antecedent cardiopulmonary disease who
appear to be abruptly “deteriorating.” If
vascular occlusion of major branches is detected,
such “deterioration” may prove to be surgically
reversible.

Etiologic Substrates. In discussing the various
conditions associated with major pulmonary
arterial occlusion, one must touch upon the
controversy as to whether the thrombi developed
in situ as a primary thrombotic process, arose
exclusively in the periphery and reached the
lung as emboli or represent embolism with
subsequent thrombotic extension. The problem
is a knotty one not subject to definitive answer
in many instances even after microscopic study.

Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

Available evidence appears to indicate that
primary in situ thrombosis does occur under
special circumstances in which the pulmonary
artery or its branches are the site of, or involved
in, an inflammatory process. Instances believed
to represent primary thrombosis have been
reported in association with pulmonary artery
aneurysms and syphilytic arteritis [27-29] and
acute arteritis secondary to inflammatory disease
of the surrounding lung [70,28,30]. In some
reports, primary thrombosis has occurred under
circumstances suggesting a generalized tendency
towards thrombosis [7], whereas in other cases
the etiology remained obscure even at autopsy.
An apparent association between direct trauma
to the chest and the subsequent discovery of
pulmonary arterial thrombosis has been noted
in young persons who were otherwise healthy
[37-33]. Trauma has also been cited as a cause of
phlebitis with subsequent embolization [34].
Of special interest is the occurrence of pulmo-
nary thrombosis in patients with chronic pulmo-
nary disease and congenital heart diseases with
left to right shunt. Chronic pulmonary disease
probably promotes thrombosis by the following
three mechanisms: (1) destruction of pulmonary
parenchyma and vascular bed with the produc-
tion of pulmonary hypertension and, ultimately,
pulmonary arterial atherosclerosis [27]; (2)
production of obliterative arteritis; and (3)
development of polycythemia [23]. Since certain
forms of congenital heart disease share several
of these same factors, the frequency of pulmo-
nary thrombosis in such patients is not un-
expected [27,28]. The incidence of extensive
thrombotic obstruction has been particularly
notable in patients with interatrial septal
defects and large left to right shunts [37,35,36].
Even though primary thrombosis of the
pulmonary artery does occur in the specialized
circumstances mentioned, most investigators
agree that chronic massive occlusion is usually
embolic in origin. In many instances—as in the
case reported herein—the history and the
presence of a known embolic source appear to
document this sequence. Silent or overt periph-
eral venous thrombosis, often in association
with right ventricular failure, may well be the
single most common source for massive em-
bolization [7,27]. However, extensive occlusion
also has been noted in association with mural
thrombosis following myocardial infarction [37],
and a significant number of reported cases have
occurred in patients with mitral stenosis.

AMERIGAN JOURNAL OF MEDICINE


272 Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

present with the patient at rest; this was markedly
accentuated during exercise, a peak level of 70 mm.
Hg being reached in the tenth minute of exercise
when the cardiac output was approximately two and
a half times the resting value. The calculated pulmo-
nary resistance remained essentially unchanged with
exercise. Although there was hyperventilation at rest
and during exercise (as indicated by the decreased
carbon dioxide tension values), arterial desaturation
was present at rest and worsened during exercise.
The A-a oxygen tension gradient, which widened
appreciably during exercise, reached a maximum
value of 65 mm. Hg during the tenth minute of
exercise.

Ten minutes after exercise, pulmonary arterial
pressure declined, oxygen saturation improved and
the A-a oxygen tension gradient narrowed. With the
patient breathing 32 per cent oxygen, arterial oxygen
saturation normalized, and pulmonary arterial pres-
sure fell to the upper limits of normal. Normal
arterial oxygen saturation was achieved with the
inhalation of 100 per cent oxygen, and the mean
pulmonary arterial pressure remained at the upper
limits of normal. Cardiac catheterization disclosed
no evidence of an intracardiac shunt.

The data suggested that the patient had primary
vascular disease of the lung. Furthermore, it appeared
that this vascular disease had resulted in a sufficient
reduction in the pulmonary capillary bed area to
produce a diffusion abnormality and pulmonary
hypertension.

An end tidal-arterial carbon dioxide tension
gradient, which was carried out while the patient
was at rest (Table m), revealed that gradient to be
27 mm. Hg. This abnormally wide gradient indicated
that a large area of the lungs was ventilated but not
perfused.

A selective pulmonary cineangiogram was carried
out next. This revealed a marked reduction in blood
flow to the middle and lower lobes of the right lung
and to the upper lobe of the left lung. The dye stream
was interrupted abruptly in these regions, and there
appeared to be a constant filling defect in the right
pulmonary artery. (Fig. 3.) The study was inter-
preted as indicating obstruction of the middle and
lower right and upper left lobar branches of the
pulmonary artery.

It was considered that these data justified an
attempt at surgical correction of. the obstructive
defects. Without correction, it was evident that the
chronic increase in right ventricular work due to
pulmonary hypertension would lead to the develop-
ment of right ventricular hypertrophy and failure in
subsequent years. Furthermore, the risk of extension
of the existing embolic occlusion to the remaining
lobar branches was thought to be considerable.

The patient was maintained on heparin therapy
throughout hospitalization. On November 1 he
underwent exploratory thoracotomy.

Tape u*
BLOOD GAS AND CIRCULATORY DYNAMICS BEFORE OPERATION

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AMERICAN JOURNAL OF MEDICINE


Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

Fic. 1. Electrocardiogram obtained on September 15,
1961, showing nonspecific changes in the S-T segment
and T wave.

and was. heard best in the third intercostal space
3 cm. lateral to the left sternal border. This murmur
increased markedly with inspiration and radiated
toward the left shoulder; it was heard well in the
neck, back and axilla on the left but was not heard
to the right of the mediastium, The liver was not
palpably enlarged. There was no clubbing or cyanosis.

Laboratory data showed a hemoglobin of 12.2 gm.
per cent, hematocrit of 38 per cent and a normal
white blood cell count. The electrocardiogram (Fig.
1) showed nonspecific changes in the S-T segment
and T wave.

A chest roentgenogram (Fig. 2A) showed relative
avascularity of the upper left lung field. The heart
was normal in configuration, but the pulmonary

Fic. 2, A, Chest roentgenogram before operation (September 1
avascularity of the upper lobe of the left lung and tenting

TABLE i
VENTILATORY STUDIES BEFORE OPERATION
Per
Pree | cent
Study Actual | dicted | of
Values dicted
Values
‘Tidal air volume (cc.) os prs
Vital capacity (cc.). 3,946 116
‘Timed vital capaci
1 second. 86 >85
2 seconds 92 >90
3 seconds. 100 100 eee
Maximum breathing capacity (L./mi 164 116 141
Functional residual capacity (cc. 2,885 |... | wee
Residual volume (cc.) 1,844 eee wes
‘Total lung capacity (cc, Ti [6420 |5,8i8 | 110
Ratio of residual volume to total lung
capacity (9). » 29 | <30
Per cent Ne after 7 2.6) <2.5)

outflow tract and major branches of the pulmonary
artery were prominent. There were pleural adhesions
on the right with moderate elevation of the right
hemidiaphragm.

Because the clinical data accumulated to this point
suggested extensive pulmonary vascular occlusive
disease, detailed evaluation of cardiopulmonary func-
tion was carried out. Ventilatory studies (Table 1)
disclosed no evidence of impairment; indeed, the
maximum breathing capacity and vital capacity were
well above the predicted normal values. Since these
data did not suggest the presence of significant
parenchymal involvement to explain the patient’s
dyspnea, arterial blood gas studies and cardiac
catheterization were performed. The patient was
studied at rest, during and after exercise, and during
periods of breathing 32 and 100 per cent oxygen. The
data (Table m) were of great interest. Pulmonary

- arterial hypertension (mean: 35 mm. Hg) was

8, 1961) showing prominent pulmonary arterial shadows,

of the right hemidiaphragm. B and C, chest rocntgenograms

after operation (January 9 and April 8, 1962) showing decrease in size of pulmonary arterial shadows.

vou. 35, aucusT 1963



270

attempt was made to relieve the obstruction.
The second patient underwent an exploratory
operation because of a lesion in the right lung,
and a lower right lobectomy was carried out
[70]. The pulmonary artery to that lobe was
surrounded by dense inflammatory tissue and
was filled with thrombi. Microscopic examina-
tion revealed a thickened vessel wall indicative
of endarteritis. Subsequently this patient died,
and autopsy revealed massive thromboembolic
occlusion of the left main pulmonary artery and
adherent emboli in the right main pulmonary
artery. The third patient underwent thora-
cotomy because of a suspected aneurysm of the
pulmonary artery. The occluded vessel and the
entire lung were resected [27].

Thus, although embolectomy or endarterec-
tomy in chronic obstruction of the major
pulmonary arteries has been suggested (22], our
review of the literature failed to disclose an
instance in which this procedure was success-
fully carried out. This presentation is the
description of a patient with this condition who
was significantly improved by bilateral pulmo-
nary embolectomy-endarterectomy.

CASE REPORT

A forty-one year old white man (K. E.) was first
admitted to a hospital on July 19, 1961, because of
increasing dyspnea of five days’ duration.

History disclosed that the patient had been an
extremely athletic and vigorous man. A routine
electrocardiogram taken one year previously had been
normal. Approximately six months prior to hospital
admission, he had dislocated his left shoulder and had
been placed in a shoulder spica for three weeks. Since
that time, he had noted mild but definite dyspnea on
moderate to severe exertion. On July 14, 1961, after
a fairly rough and extended airplane trip, he became
nauseated, weak and dyspneic. The next day he noted
diarrhea and increasing dyspnea. His temperature
was recorded at 100.4°r., and at rest, his pulse ranged
from 104 to 120 beats per minute. The fever and
diarrhea disappeared in three days, but increased
dyspnea and tachycardia persisted. An clectro-
cardiogram showed sinus tachycardia and T wave
inversion in leads V; and V2. Two days later (July
19), the electrocardiogram was unaltered, but a fric-
tion rub was heard over the precordium, and the
patient was admitted to the hospital.

Physical examination on admission revealed nor-
mal temperature, blood pressure and pulse. The
patient was moderately dyspneic at rest. There was no
cyanosis or neck vein distention. The lungs were
clear. The heart was not enlarged. There was a
“to-and-fro” friction rub in the fourth intercostal

Chronic Thrombotic Obstruction of Pulmonary Arteries—Houk et al.

space at the left sternal border. A high-pitched, blow-
ing systolic murmur was heard over the base of the
heart that radiated toward the left shoulder and into
the back. The second heart sound in the pulmonic
area was greater than that in the aortic area and was
widely split. A systolic gallop sound was present.
The remainder of the examination revealed no
abnormalities.

The electrocardiogram on the day of admission
showed T wave inversion in leads u, aVF and V;R
through Vs. A chest roentgenogram suggested
moderate enlargement of left pulmonary artery, The
hemoglobin, hematocrit, white blood cell count,
urinalysis and serum glutamic oxalacetic trans-
aminase (SGOT) were within normal limits.

‘The initial clinical impression was that of a viral
myocarditis, The patient was placed at bed rest and,
because of the persistence of the pulmonic systolic
murmur, the possibility of a pulmonary arteriovenous
fistula was entertained. Arterial oxygen saturation
determined with the patient at rest and breathing
room air was reported to be 95 per cent. On July 21
the arm to lung circulation time was seven seconds
and arm to tongue, twenty-seven seconds. Venous
pressures were normal. On July 25 the patient com-
plained of pain in the right groin, and by July 26 this
had developed into clinical thrombophlebitis. He was
given heparin on July 27 and 28. A single dose of 60
mg. warfarin sodium given on July 27 clevated his
prothrombin time into the usual therapeutic range,
and it was maintained in that range with warfarin
sodium therapy. On August 3 while his prothrombin
time was recorded at fifty-nine seconds (control
thirteen seconds), he started to move about; he
experienced new tenderness in the calf of the right
leg and was again placed at bed rest. The following day
he experienced pleuritic pain on the right side of the
chest, and a friction rub was heard over that area. He
remained at rest until August 27 when anticoagulant
therapy was discontinued, and he was permitted to be
ambulant again. During the course of this hospitaliza-
tion serial electrocardiograms revealed inverted T
waves in leads V; through V3 until July 26. By August
21 the T waves were inverted only in leads V,R and V}.

The patient was transferred to the U. S. Naval
Hospital, Bethesda, Maryland, for evaluation on
September 15. On admission physical examination
revealed a well developed, well nourished, muscular
white man who was not dyspenic at rest. The vital
signs were within normal limits. The neck veins were
not distended at 30 degree elevation, and hepato-
jugular reflex was not elicited. The lungs were clear
to palpation, percussion and auscultation. The heart
was not clinically enlarged; normal sinus rhythm was
present. The second heart sound was widely split on
inspiration but closed normally with expiration. The
pulmonary component of the second heart sound was
accentuated. There was a grade 2 blowing holo-
systolic murmur which broached the second sound

AMERICAN JOURNAL OF MEDICINE


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19.

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21.

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23.

24.
25.

26.

27.

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