Patent Ductus Arteriosus in the Adult

Actn Medica Scandinavicr. Vol. CLV, fasc. 11, 1966.

From the lVth Medical Service and the Central Laboratory, S:t Erik’s Hospital and the Surgical Clinic, Sabbatsberg’s Hospital, Stockholm, Sweden.

Piltent Ductus Arteriosiis in the Adult. BY

H A R D ELIASCH, KERSTIN ERIKSSON and LARS WERKO.

(Submitted for publication April 25, 1956.)

Interest in patent ductus arteriosus has increased rapidly since this disorder became amenable to surgical correction (Gross 1939). Operative closure of the ductus is, as a rule, readily accomplished in the uncomplicated case (Crafoord 1944; Gilchrist 1945; Gross and Longino 1951; Ekstrom 1952). If pulmonary hypertension has developed operation becomes hazardous and the outcome poor if the shunt is reversed (Johnson, Werner, Kuschner and Cournand 1950; Dammann, Berthrong and Bing 1953; Hultgren, Selzer, Purdy, Holman and Gerbode 1953; Gordon, Donoso, Kuhn, Ravitch and Himmelstein 1954). The longevity of patients with patent ductus is known to be decreased (Bullock, Jones and Dolley 1939; Keys and Shapiro 1943), and the risk of complicating subacute bacterial endocarditis has not yet been eliminated. On account of this it seems reasonable that a patent ductus should be closed some time during childhood (Gross and Longino 1951; Mannheirner 1945).

Patent ductus arteriosus is not an uncommon congenital disorder in the adult. Those patients with symptoms and a moderate degree of pulmonary hypertension should generally be operated on (Cournand, Baldwin and Himmelstein 1949; Silver, Kirklin, Ellis and Wood 1954). Many patients, however, are free of symptoms even as adults. Whether the asymptomatic adult patient as well as those having excessive degree of pulmonary hypertension should be operated upon is still a matter of debate (Campbell 1955). I n an attempt to clarify this problem clinical and physiologic data have been compiled from a study of seventeen adult patients with patent ductus arteriosus. Studies of cardio-pulmonary and renal hemodynamics were made in the resting patient and during a graded exercise test. Follow up studies were carried out in six patients to determine the effect of operative closure of the ductus.

The work described in this paper was aided by grants from the Swedish Medical Research Council, the Knut and Alice Wallenherg Foundation and the Swedish Association Against Tuberculosis.

136 HARALD ELIASCH, KERSTIN ERIKSSON AND LARS WERKO.

MitteI*inl and methods of sludy.

The material consisted of seventeen patients with patent ductus’ arteriosus, referred to the hospital for study. Selection was random. The diagnosis was made from typical auscultatory findings and/or from the results obtained at cardiac catheterization and, in eight patients by selective angiocardiography or aortog- raphy. Diagnosis was further confirmed a t operation in eleven patients.

I n each patient a detailed case history was taken and the usual bedside examination made. In some patients phonocardiogram was recorded using a calibrated magnetophonic microphone.

The size of the heart was determined roentgenologically according to the method of Liljestrand, Lysholm, Nylin and Zachrisson (1939).

Electrocardiograms were recorded using standard limb leads and precordial leads.

In all patients having pulmonary hypertension, and in two with normal pulmonary pressures selective angiocardiography by Gidlund’s apparatus (Gidlund 1956) was performed by Drs. Kjellberg and Rudhe a t the Children’s Hospital of Karolinska Sjukhuset (Kjellberg, Mannheimer, Rudhe and Jonsson 1955) and Dr. .Tonsson a t Sodersjukhuset, Stockholm.

Electrokymographic examination of the heart and great vessels was done in most patients by Dr. Rudhe (Rudhc 1956).

Pulmonary function studies including the determination of the total lung capacity with its subdivisions were performed in six patients. The residual air was measured by the helium dilution method. The total amount of hemoglobin was determined by the carbonmonooxide method according to Sjostrand (1948).

These two studies were done a t the Department of Clinical Physiology, Karo- linska Sjukhuset, Stockholm.

Right heart catheterization and simultaneous renal function studies were carried out in the morning with the patient recumbent and in the postabsorptive state. An indwelling catheter was placed in the urinary bladder. Para-amino- hippuratc was given intramuscularly according to Bucht (1949) and inulin intra- venously a t the beginning of the study.

The pulmonary artery was catheterized according to Cournand and Ranges (1941) and Lagerlof and Werko (1949). An indwelling needle was placed in the brachial artery. In some patients one catheter was placed in the pulmonary artery and another in the right auricle. Cardiac output was measured by the Fick method with simultaneous sampling of blood from the brachial and pulmonary arteries and collection of expired air. Blood sample from the right auricle was obtained ximultaneously or immediately after. Pressures were recorded by strain gauge manometers or Tybjaerg-Hansen electrical manometers (1949).

About thirty minutes after the heart catheters had been introduced, the first resting cardiac output was determined and pressures recorded. Some patients then performed exercise equalling about 200 kilogrammeters per minute by pedalling a cycle ergometer for twelve to fifteen minutes. Pressure and flow measurements

PATENT DUCTUS ARTERIOSUS I N THE ADULT. 137

were repeated toward the end of exercise. This was not stopped for these deter- minations (Eliasch 1952).

Clearance periods were obtained every fifteen to twenty minutes by sampling blood and emptying the urinary bladder (W-erko, Varnauskas, Eliasch, Ek, Bucht: Thomassoil and Bergstrom 1954).

In eleven patients surgery was performed by Dr. Crafoord and his associates a t the Surgical Clinic of Sabbatsberg's Hospital, Stockbolm.

Hesults of clinical studies.

Tables 1 a and 1 b show the clinical findings. The age ranged between 18 and 47 years. Thirteen were females, four males. The material was divided into two groups after the level of the mean pulmonary arterial pressure. In the one group this was below, in the other above twenty-five millimeters of mercury. Patients in the latter group were, by definition, considered to have pulmonary hypertension.

Table 18. Clinical data obtained in eleven patients with patent ductus arteriosus having

normal pulmonary arterial pressure. Symbols: LVS = left I entricular strain. RVS = right ventricular strain. N -= normal. M = rMachinei-y murmur)). S = systolic murmur. D = Diastolic murmur. Grading of murmur was made after Levine (1945) (Roman numbers).

I Murmurs I Heart 2 I Blood I -.- I.....<

. I I -. 1 Svmutoms

1 332 141 487 545

1 612 63 1 ti90 710 765 802

27 F 1.62 ' 47 F 1 1.6.1

i 29 , M I 1.81

155175 470 140/85 370 150185 560

l60/80 355 150/75 350 130160 490 13oj90 440 130180 370

LVS N K s K N

LVS LVS S s 110160 390

901 36 F 1 1.57 - + 1 + 1 0 140190 1 400 N -

M V I M 111 M 111 M 111 M I1 M I11 M 111 M I V M I11 M I11 M IV __-

Apes

0 s I1 S I1

0 0 0

0 s v SIV I 1

____ SF I

Electrokymographic recording of the pulmonary artery and the aorta was obtained in the majority of patients. Diagnosis of disease was not aided by this method of investigation.

Selective cardioangiography was performed in all patients with pulmonary hypertension and in one, No. 690, having normal pulmonary pressure. The ductus was clearly demonstrated in each patient.

Pulmonary function studies were made in six patients. No major abnormalit'ies were found.

138

Blood pressure mmHg

HARALD ELIASCH, KERSTIN ERIKSSON AND LARS WERKO.

Table lb. Clinical data obtained in s i x patients with patent ductus arteriosus having

elevated pulmonary arterial pressure. Symbols: See table 1 a. AF = Auricular fibrillation.

1 Murmurs _- __ Heart ~

' ECG 1 ~ Base ~ Apex I

- - 0

3 - 20 31

41

34

40

18 -

180/55 130/80

205/75-0

F M

F

F

M

F -

670 LVS M IV 720 1 AF S IV

LVS D IV 660 I LVS S 111

1.54 1.68

1.59

1.12

1.87

1.33

Symptoms

+ + + + + + -

D I11 150/90 RVS S IV

D I1 130/40 1 ::: ~ LVS 1 M I11

s I V 0

s I11 0

s I11 D I1 0 . 125/60--0~ 530 i LVS I , M IV

The total amount of hemoglobin exceeded the predicted value in two of the patients with normal pulmonary pressures (Nos. 487 and 690). These patients had slight arterial unsaturation a t rest. Of the six patients with pulmonary hypertension three had increased amounts of hemoglobin. Patient No. 647 with arterial unsaturation and cyanosis had normal values (tables 2 a and 2 b).

Table 2s. T h e amount of measured and predicted total hemoglobin content of the body

in nine patients of patent ductus arteriosus with normal pulmonary pressure. Postoperative observations were obtained in two patients.

Total Hb ~~ .~ ~ . -

- Preop. ~~ I Postop. Case No. ~ ~

Predicted ~ Measured 1 Predicted 1 Measured

352 441

4871525 545 612

631/- 690/721

765 901

455 .. .

545 560 460 510 450 530 400 430

510 I 445 495 - 690 - 560 - 385 - 385 - 650 I - 435 - 435 420

Normal pulmonary arterial pressure.

The majority of patients with normal pulmonary pressure had no symptoms, but four complained of exertional dyspnea and three of fatigue. History of precordial pain was given by two.

PATENT DUCTUS ARTERIOSUS TN THE ADULT. 139

I

I Case KO. I

Total - H b I _ _ -

h o p . Postop. - -

430 42.5 365/425 I 610 ' 730

63!5 6471875 540 h.0

3 651 668 , 730 700 742 360 420

The heart size was within normal range in a11 but three patients. In these slight enlargement of the left ventricular contour was observed, increasing the heart size above 450 ml per square meter body surface area.

The electrocardiogram was normal in eight patients. In three depression of the S-T segment was present as in left ventricular strain.

In all patients typical umachinery murmuru was heard, in four supplemented with an apical systolic murmur.

Cyanosis was not present in any of the patients. There were no signs of retarded body growth.

KO one of the patients studied had received digitalis within a month before the time of cardiac catheterization.

Elevated pulmonary arterial pressure.

Varying degrees of physical incapacity were complained of by all except one patient. History of precordial pain was given by two.

The heart was roentgenologically enlarged in all but the one patient, who gave no history of dyspnea or fatigue.

The electrocardiogram showed mainly changes of the S-T segment and the T waves as in left ventricular strain in five patients and right ventricular strain in the remaining (No. 647). One patient, No. 365, had auricular fibrillation. In this patient marked kyphoscoliosis of the thoracic spine was present.

In three patients ,machinery murmuru was heard over the base of the heart; in two of these an apical systolic murmur was present as well. In the remaining three patients both systolic and diastolic murmurs were heard a t the base of the heart, but typical cohtinuity could not be perceived. Auscultation of the heart was repeatedly performed in these patients and it was observed that the intensity of murmurs could undergo marked changes from one day to another. Phonocar-

140 HARALD ELIASCH, KERSTIN ERIKSSON A N D LARS WERK6.

diogram was made with a calibrated magnetophonic microphone in some patients. No additional information on the topography of murmurs was obtained thereby.

Cryanosis of the legs and the lips was observed in one patient. No. 647, in whom clubbing of the fingertips was also present.

Postoperative findings

A11 patients with elevated pulmonary arterial pressure and five of those with normal pressure in the pulmonary circuit were operated upon. They w-ere considered to have symptoms and/or increase in heart size of enough severity to warrant operation. None of these patients, when asked, were against surgery. The six patients that were not operated upon had normal heart size and estimated shunts were small. They had no symptoms and were not convinced of the desira- bility of operation.

In the five patients with normal pulmonary pressures operation was uneventful in four (Case No. 352, 631, 690 and 901). The continuous murmur disappeared in all. Considerable technical difficulty was encountered during operation of patient No. 487 because of a short and wide ductus. that eventually was ligated a t two levels. The continuous murmur disappeared after ligation, but reappeared three weeks after operation. At the postoperative heart catheterization the catheter was again passed from the pulmonary artery through the ductus into the aorta.

Of the six patients with elevattd pulmonary arterial pressure the operation and immediate postoperative course was uneventful only in the oldest patient of the serifs. Xo. 588, who improved markedly. The heart size decreased slightly and the peripheral arterial pulse pressure diminished. One patient, KO. 792. died during surgerv from rupture of the pulmonary artery before the ductus was dissected free.

In patient No. 647, who had right to left shunt, it was decided to occlude the ductus for a short time before ligating. Pressure measurements were performed during operation (fig. 1). Immediately after occlusion the pulmonary arterial pressure rose while the aortic decreased. The ductus was occluded for 30 minutes. As no further change occurred in these pressures during that interval it was decided unwise to close the ductus completely. A cellophane ligature was instead tightened around the ductus, decreasing its circumference by about half with the idea that the cellophane might gradually shrink further. The immediate postoperative course was one of slight improvement and cyanosis almost disappeared. Three months after operation this patient developed right heart failure and her peripheral cyanosis increased.

In patient No. 288 the ductus was wide and short, and the aorta had to be clamped for about twenty-five minutes before the ductus was divided. The ductus was well closed and the heart size decreased markedly after operation. This patient, however, developed paraplegia, invalidizing her.

Patient No. 365 had auricular fibrillation. The course of’ operation went very well. Shortly afterwards an increase in heart size was observed and the patient developed signs of cerebral and peripheral arterial embolism. These cleared up and

PATENT DUCTUS ARTERIOSUS IN THE ADULT. 141

Clamping patent duc 5.

-* - ,1 i

I ,

\ \ \ +

, RA. '-J ---f -. . f -.. .. Y' .

- I .-I-- /-------*,- i ,-- .- , -

- *_ --..<--.--

L

u r--.--zj..-.-."-t.-+-..-. .---. - _- L-

FtwM obstructm by operation

-- _I_cI

&h i37/95mno /tl,

" % \ "

i

I

i ' ---...J

\ \ z

-.cr i-

- t ', ' i.

"u --.. \

*

Pig. 1. Strips of simultaneous recordings of electrocardiogram, aortic and pulmonary arterial pressure curves obtained during operation with the heart and great vessels exposed in patient No. 647, who had reversal of shunt. The first strip shows recordings before, the second during short time clamping of the ductus and the third strip a t the time when the clamp was released. It is shown that as the patent ductus is clamped there is a diminished pulse pressure in the aorta, while the pulmonary arterial pulse pressure R S well as mean pressure rise. Abnormalities vanish as the clamp is released. The records on the fourth strip were obtained when the ductus had been clamped for 27 minutes. Last strip recordings were obtained when the cellophane ligature by purpose only partially obstructing the durtus, had been

applied.

142 HARALD ELIASCH, KERSTIN ERIKSSON ANC LARS WERKO.

the only residual symptom left was a hemianopsia. The heart size eventually decreased to a smaller figure than before operation.

Before operation, patient No. 651 had had endomyocarditis, considered adequately treated with antibiotics. The heart size slowly increased after operation by three times of its original figure, presumably due to reactivation of the endomyocarditis. After treatment with penicillin and streptomycin it decreased to about the same size as before surgery. The patient was discharged free of symptoms half a year after operation.

Operation did not alter total hemoglobin except for patient No. 588, who had a relatively large shunt before surgery. After surgery the total hemoglobin decreased in this patient. In patient No. 647, who developed right heart failure after operation the amount of total hemoglobin rose.

To summarize, out of eleven adults operated because of symptoms and/or evidence of cardiac strain, good result and no complications observed, were noted in only five. Two patients, after prolonged hospitalization due to postoperative complications, finally arrived a t satisfactory condition. One patient died during operation and one was invalidized by paraplegia. Reappearance andfor aggrava- tion of preoperative symptoms and signs was observed in two.

Itesults of hemodynamicsl studies.

Right heart catheterization data obtained in patients with normal pulmonary pressures are shown in table 3 a . Eleven were studied at rest; the reaction to exercise was studied in nine. At rest the difference of blood oxygen content between the pulmonary artery and the right auricle ranged between + 3.12 and - 0 .27 volume per cent. The difference was equal to or higher than 1.2 volume per cent in five patients. On exercise the difference ranged between + 2.90 and + 1.34.

The oxygen saturation of the systemic arterial blood ranged between 98.3 and 85.8 per cent, and was below 90 in two patients (Nos. 487 and 690). On effort no substantial change was observed but for patient No. 690, where it increased from 85.8 to 92.5 per cent.

The calculated pulmonary blood flow, expressed as liters per minute per square meter body surface area, varied a t rest between 11.3 and 2.8 liters and on effort between 11.0 and 4.5 liters. Exercise caused a marked increase in six patients (Nos. 545, 631, 690, 765 and 802).

The systemic blood flow, also expressed as liters per minute per square meter body surface area ranged a t rest between 5.4 and 2.0 liters and on effort between 7.9 and 3.6 liters. Exercise caused a marked increase in five patients. I n four of these the pulmonary blood flow rose as well (Nos. 487, 631, 765 and 802).

The right auricular pressure was within normal limits a t rest and did not change on effort.

The systemic arterial pulse pressure tended to be wide in most patients. On exercise no substantial change was observed.

Tab

le 3a

Hem

odyn

amic

dat

a ob

tain

ed i

n el

even

pat

ient

s with

pat

ent d

uctu

s ar

teri

osus

hav

ing

norm

al p

ulm

onar

y pr

essu

re a

t res

t (R

). Th

e re

spon

se

to e

xerc

ise (

E) w

as s

tudi

ed i

n ni

ne. M

easu

rem

ents

inc

lude

the

oxyg

en c

onsu

mpt

ion,

blo

od c

onte

nt o

f ox

ygen

, art

eria

l ox

ygen

sat

urat

ion,

pr

essu

res

in t

he r

ight

aur

icle

(R

A),

the

right

ven

tricl

e (R

V),

the

pulm

onar

y ar

tery

(P

A),

the

pulm

onar

y ve

nous

cap

illar

ies

(PC

V) a

nd

the

brac

hial

art

ery

(BA

). Ca

rdia

c ou

tput

was

exp

ress

ed a

s ca

rdia

c in

dex

(C. I

.) i.

e. c

ardi

ac o

utpu

t pe

r m

inut

e in

lite

rs p

er s

quur

e m

eter

bo

dy s

urfa

ce a

rea.

Str

oke

volu

me

was

exp

ress

ed a

s str

oke

inde

x (S

. I.)

i. e.

stro

ke v

olum

e pe

r be

at i

n m

l pe

r sq

uare

met

er b

ody

surf

ace

area

. S =

sys

tolic

, D

= d

iast

olic

and

M =

mea

n pr

essu

re.

Cal

cula

tion

of p

ulm

onar

y fl

ow:

Cal

cula

tion

of s

yste

mic

flo

w:

88

109 63

73

79

86

44

52

66

66

76

59

41

61

77

87

65

67

61

68

c. 0

, = -*

- 0

co

nsum

ptio

n 0,

cont

ent

of B

A - R

A

-

121

133 86

97

104

106 64

76

91

86

99

79

64

76

104

108 82

85

85

85

0,

cons

umpt

ion

96 %

of

art.

0,

capa

city

- 0,

con

tent

PA

c.

0. =

95

92

109

117

104

116 68

96

92

11

0 70

99

70

110 88

120 72

83

87

92

11.3

11.0

4.8

5.2 4.3

5.8

5.7 7.4 4.6

4.5

4.7

7.2

2.9

7.4

4.1

9.3

2.8

5.5

5.0

3.9

:; 59

45

41

33

55

51

78

50

41

54

28

55

40

48

Y

H $ . +I +

bP

0

k

I M

Blo

od f

low

I

3

-

0,

con-

um

ptio

r m

l/min

.

-

Art

. 0,

ca

paci

ty

volu

me

per

cent

-

krte

rial

0

, sa

tura

- ti

on

%

93.3

94

.0

93.3

93

.6

88.5

88

.4

98.3

95

.0

93.5

91

.2

94.9

93

.8

85.8

92

.5

97.1

97

.3

90.0

90

.0

91.6

93

.2

-

Blo

od p

ress

ures

mm

Hg

0, c

onte

nt

volu

me

per

cent

P

ulse

-

Rat

e c.

I.

beat

/ I/

min

/me B

SA

2ase

N

o.

-

352

441

487

545

612

631

690

765

802

740

901

~

BA

tA

M 3 0 -2 -1 0 -2 2 1 -2 1

0 4 0 0 0 0 3 1

~ - -

-

-

PA

m

l/be

BE

Pulm

.

119

117 44

44

41

50

84

77

50

41

66

73

42

68

54

78

39

66

57

41

--

-

RA

P

A

~

Syst

. -

4.5 7.9

4.1

4.2

3.0

4.7

4.0

4.3

3.1

3.6

3.9

5.1

5.4

5.6

3.6

6.5

2.0

4.6

3.5

4.4

M

19

19

12

17

18

25

14

17

16

14

14

14 9 13

14

16

11

13

18 9

I

-

-~

S 23

22

17

23

26

33

21

29

33

22

18

23

13

17

19

21

16

18

24

15 -

-

D

12

12 8 10

13

19

10

13 6 8 5 8 7 10 9 11 7 8 12 7 -

-

~

M 9 8 3 7 8 8 11 2 4 8 9 6 7 8 11 2 2 13 3 -

-

- _

.

S 158

167

126

141

150

150 87

110

117

140

129

126

114 93

12

7 14

6 10

6 10

8 11

9 12

6 -

-

-

R

E

R

E

R

E

R

E R E

R

E

R E

R

E

R

E

R

R -

262

442

226

405

271

536

250

423

256

514

193

489

218

679

203

698

199

680

209

181

11.6

6 11

.90

13.3

2 11

.28

12.2

7 11

.20

11.9

4 10

.27

11.3

6 6.

62

11.8

7 8.

70

16.5

0 11

.41

13.6

8 9.

33

11.6

8 9.

26

11.6

2

12.8

4

14.2

9 13

.70

14.2

6 12

.62

15.3

9 14

.10

13.0

9 12

.17

12.5

4 9.

16

12.5

9 10

.92

16.4

5 14

.25

14.6

0 11

.51

14.3

7 11

.75

13.3

8

12.9

5 - 15

.29

15.3

9 16

.39

16.6

3 17

.54

17.8

2 15

.80

15.5

7 15

.55

15.3

7 15

.17

15.0

6

19.2

1 19

.68

17.4

9 16

.56

17.1

6 17

.46

15.1

9 15

.47

__

16.3

9

17.5

7 17

.76

19.8

2 20

.22

16.0

7 16

.38

16.6

3 16

.84

15.9

8 16

.05

22.3

8 21

.27

18.0

1 17

.02

19.0

5 19

.40

16.5

8 16

.60

16.7

7

Ttrb

le 3

b.

Heq

nody

ruiva

ic da

ta o

btui

iicd

in s

ix p

utie

nts

with

put

ent

duct

us a

rter

iosu

s h(

zeiqa

g el

ct~t

rtctl p

iitno

ttury

pw

smir

e at

res

t. Th

e rc

spov

we

to e

xerc

ise w

us s

tudi

ed i

n fo

ur.

Sym

bols

see

tah

le 3

a.

3 -

-

- 7 8 7 4 16

17

-

-

Cas

e N

o.

-

365

647

651

792

288

588

__

125

143 97

98

113

115

103

130

145

175

- - -

R

E

R

E

R

E

R

E R

R -

-

33

56

126

140 45

48

95

124 51

61

I 1

0,

cont

ent

I

0,

1 vo

lum

e pe

r ce

nt

1 Art

. 0

,

19

36

70

75

20

20

56

71

29

35

-

274

514

281

467

285

653

202

548

200

264

__

_

73

95

87

111 81

101

81

130 86

91

RA

PA

7.8

9.6

1.9

2.0 7.0

9.7 7.5

6.3

9.2

11.8

-

12.7

4 11

.88

10.3

8 5.

76

10.2

9 10

.91

10.3

0 8.

35

7.63

13

.15

3.2

5.0

2.7

3.5

3.1

6.8

2.8

5.4

2.1

-

16.3

1 15

.15

10.3

1 .5

.26

13.5

1 12

.44

13.6

2 9.

78

12.6

0 15

.51

91

44

101

53

22

31

18

31

87

38

96

67

93

35

49

42

107

25

capa

city

~

volu

me

BA

per

cent

-

17.8

2

16.4

1

15.1

9 16

.04

15.6

4 15

.98

13.7

0 16

.19

17.9

5

13.5

5

-

17.1

7 19

.42

19.5

8 19

.84

16.3

3 16

.56

16.2

4 16

.98

14.6

0 17

.62

Blo

od p

ress

ures

mm

Hg

brte

rial

0,

-

R.4~

RV

sa

tura

- ti

on

93.0

-3

92.1

-2

83.8

0

93.0

1

96.9

-2

96.3

3

94.1

-2

93

.8

2 93

.6

2

68.3

-2

PA

-

M

25

45

90

98

30

31

72

89

38

43 -

-

D

71

92

59

60

51

50

51

75

56

71

-

-

M 90

120 73

72

72

72

72

94

90

100 -

-

i B

lood

flo

w

min

. -~

Pulm

.


The pulmonary capillary venous pressure ranged within normal limits and no significant change was recorded on exercise. The pulmonary arterial pressure, by definition normal a t rest, underwent no substantial change on effort but for patient No. 487, where it increased from eighteen to twenty-five millimeters of mercury.

Table 3 b shows data obtained by right heart catheterization in patients with elevated pulmonary arterial pressure. Six were studied a t rest while the reaction to exercise was observed in four of these. The difference of blood oxygen content between the pulmonary artery and the right auricle a t rest varied between + 4.97 and - 0.07 volume per cent, considerably exceeding + 1.2 in five patients. On effort a decrease in the difference was noted in two.

The oxygen saturation of the systemic arterial blood was within normal range in all patients except for No. 647 (83.8 per cent). In this patient the saturation decreased to 68.3 per cent on exercise.

The calculated pulmonary blood flow expressed as liters per minute per square meter body surface area varied between 11 .8 and 1.9 liters. On effort between 9.7 and 2.0 liters. A moderate increase was observed in two. Patient No. 647, who had arterial oxygen unsaturation had only 1.9 liter in pulmonary blood flow, and no change occurred on exercise.

The systemic blood flow expresscd as liters per minute per square meter body surface area, ranged between 5.0 and 2.1 liters a t rest and between 6.8 and 3.5 liters on exercise. The flow increased on effort in all patients.

The right auricular pressure ranged within normal limits in all patients and there was no change on effort.

The systemic arterial pulse pressure tended to be wide in all patients. An increase in diastolic pressure was observed in two patients on effort.

The pulmonary capillary venous pressure was pathologically elevated in two patients, Nos. 288 and 588. The reaction to effort was not studied in these.

The pulmonary arterial pressure, by definition pathologically high in these patients increased further in three out of four patients that were exercised (Nos. 365, 647 and 792). Patient No. 647, with oxygen unsaturation and relatively low pulmonary blood flow had the highest pressure, 126 over 70, and 90 as mean pressure.

Table 4 shom results obtained on the postoperative study. Two patients (Nos. 4871525 and 6901721) with normal pulmonary pressure were investigated after operation. In patient No. 487, where operation had been technically unsuccessful an appreciable shunt was still present, however, less than before.

Four of those patients having pulmonary hypertension before operation were studied postoperatively. The pulmonary pressure was measured in three. In patient No. 2881330 the pulmonary arterial pressure decreased from thirty-eight to eight millimeters of mercury with a concomitant fall in the pulmonary capillary venous pressure from sixteen to three, and the pulmonary blood flow from 9.2 to 6.3 liters. In patient No. 588/643 the pulmonary arterial pressure decreased from forty-three to fourteen and the capillary venous pressure from seventeen to three. Here the pulmonary blood flow fell from 11.8 to 4.6 liters. In patient No. 651/668 the pressure in the pulmonary artery fell from thirty to eighteen and in

Tab

le 4

. W

m

Hem

dyna

mic

dat

a on p

osto

pera

tive

stud

y (li

gatio

n of

duct

us) o

btai

ned

in s

ix p

atie

nts

(R).

The

resp

onse

to e

xerc

ise w

as s

tudi

ed i

n fo

ur

P

(E).

Patie

nts

Nos

. 487

1525

and

690

1721

had

nor

mal

pul

mon

ary

pres

sure

bef

ore

oper

atio

n, t

he o

ther

s el

evat

ed.

- - -

R

E

R

E R R E R

E

-

-

Puls

e R

ate

beat

/ m

in.

-

C. I

. /m

in;m

' B

SA

Blo

od p

ress

ures

mm

Hg

___

~ -

0,

cont

ent

volu

me

per

cent

O

8 :o

nsum

ptio

n m

llmin

.

s. I.

ol

/bea

t/m'

BSA

B

A

11

PA

PC

V I

~

RA

RA

~

-

MIS I

-1 14

~

BA

__

PA

D(

M~

M(

S

4871

525

6901

721

2881

330

'5881

642

'6471

875

273

337

247

662

305

212

281 -

-

"4 160

11.3

3 9.

61

16.1

6 11

.77

11.0

3

11.6

8 10

.33

15.1

5 11

.56

12.1

7

13.6

2 14

.29

19.1

1 19

.92

15.3

0

15.6

4 15

.50

19.8

0 19

.52

15.2

5 15

.09

14.6

2 93

.2

14.8

6 96

.2

130

128 86

111 87

88

106 95

121

8.5

5.2

4.3

5.5 6.3

4.6

4.1 -

-

3.3

3.9

66

40

50

50

73

52

45 -

-

38

40

II

!

I 78

' 93

I 94

P~ ;:

104

, 112

68

94

66 1

93

1

6 9

6 11

4 8

12 -

115

20.4

0 ~

93.7

21.3

0 1

93.5

16.3

6 93

.5

-2 i 2

1

16.3

7 95

.5

0 28

16

.71

92.8

-4

1

32

I 21

.13

93.7

I - I -

20.78

93

.9

- -

16.1

9 94

.2

1 30

16

.30

92.6

0

35

3~

8 3

11

34

3 '

14

3 15

7 9

16

2 14

3 I

-

12.6

7 11

.03

~ 11

.14

- I

- -

129

-1

-

-

134

-I

-

-!

-

651/

668

R

IE

-

10.7

9 -

8.76

9

18

1 1

114

69

85

88

13

21

1 5

122

68

88

98

I I

Sym

bols

see

tab

le 3

a.

Exer

cise

loa

d in

the

se p

atie

nts

was

onl

y 70

kg.

PATENT DUCTUS ARTERTOSUS I N THE ADULT. 147

ml/rnin/l.73 m2 rnlpninjl.7s m2

the pulmonary capillaries from seven to one. The pulmonary blood flow decreased from 7.0 to 3.9 liters.

Of these patients two demonstrated increase in the systemic blood flow. Arterial oxygen saturation was within normal limits in all patients. The response

to exercise was essentially normal in the few patients so studied. In patient No. 64718'75 having reversed shunt before operation pulmonary pres-

sures and flows were not obtained a t the postoperative study. In this patient pressures were recorded during the course of surgery. The results have been given before in this paper (fig. 1).

Table 5 demonstrates results from the renal studies. The renal plasma flow, as measured by the clearance of para-amino-hippurate, was within normal range or only slightly lowered in patients with normal pulmonary pressure, but markedly decreased in four out of six patients with elevated pulmonary pressure. The filtration rate (inulin clearance) followed in essence the similar pattern.

ml/rnin/1.73 r n z

Table 6 a. Renal clearances of para-amino-hippurate (PAH) , inul in and endogenous creatinine and urinary sodium excretion in fifteen patients with patent ductus arteriosus. T h e effect of

exercise was studied in nine patients.

- - -

389 510 285

83 88

146 91

119 144

5 a.1

352 44 1 487 545 612 690 740 765 901

5 a. I1 288 365 588 647 651 792

Rest

419 433 385 630 518 452 450 467 600

353 267 564 280 445 303

Effort Rest ~ Effort Rest

I I

- I 122

406 1 91 1 78 1 66 574 116 I 112 85 - I in5 - I RF( _ _ _ _ --

90 i 1 '57 1 79 527 -

Elevated PA pressure

- - - 99

115 125

112 93

112 70

102 82

Effort

- 79 82

105 54 99

118 -

-

- - - 71

111 82

Urinary Na+ excretion

pEqv/min

Rest

- 194 319 221 38 1 77

476 293 223

- -

270 605 343 126

Effort

- 116 314 252 110 38

405 -

-

- - -

497 304 127

The urinary excretion of sodium dropped during exercise in four of those nine patients where this was studied. Only one had pulmonary hypertension.

Postoperative studies of the renal function were made in seven patients. Of those three who had normal pressure before operation renal plasma flow in-

11-563337. Actn med. Scandinau. V o l . CLV.

148 HARALD ELIASCH, KERSTIN ERIKSSON A N D LARS WERKO.

Inulin

ml/rnin/1.?3 m*

Taltle 6 I).

Postoperative studies on renal clearances of para-amino-hippurate ( P A H ) , inulin and endogenous creatinine and urinary sodium excretion in seven patients. The response to

exercise was studied in three.

Endogenous ' Na+ excr&ion ' uEqv/min Creatinine

ml/rnin/l.?t m* I

Case No.

108 - 86 -

153 164 118 85

I Renal Clearance - -~ Urinarv

136 75 89 62

1 Rest 1 Effort ~ Rest 1 Effort 1 Rest I Effort

5 b.1 3521- I 376 I - I 93 l - i l O 6 I - ~~

- - ' 76 I 566 1 ~ 1% I -74 I 79

5 b. I1 288/330 365/425 5 8 8 / 6 4 2 647/875

479 284 569 215

- -

581 138

Elevated PA pressure

- -

98 49

Rest

- 119 163

- -

306 168

Effort

- - 147

- -

31 2 83

creased markedly in patient No. 690; no substantial change was observed in the remaining, in one of whom the ductus became patent again shortly after operation (No. 4871525). Four patients had pulmonary hypertension before operation. Suc- cessful surgery was performed in two patients, Nos. 288 and 588. In patient No. 288 the renal function improved. No change was observed in patient No. 588, who, however, had normal clearance values before operation.

Discussion.

Interest has been directed to the study of pulmonary hypertension in the adult patient with patent ductus arteriosus during the last decade. Reports on hemodynamic studies in the uncomplicated case are scanty. The reason for this seems obvious. If diagnosis is assessed by the typical auscultatory finding, the patient is free of symptoms and the cardiac contours lack gross pathology, i t is generally accepted that the patient may be operated upon without further hemodynamic studies. However, if no typical murmur is present and the patient has symptoms, right heart catheterization is generally needed for the establishment of diagnosis. In this group of patients pulmonary hypertension is likely to be present.

All patients with patent ductus arteriosus admitted to the hospital during the last five years were studied in order to appraise the occurrence of different complications in patients with longstanding patent ductus arteriosus. The effect of exercise was also studied in order to establish whether physical effort in patients


with uncomplicated patent ductus arteriosus constitutes an added strain on the myocardium.

Most patients had normal pressures in the pulmonary circuit, both a t rest and during exercise. There was no correlation between the size of the estimated shunt and the pulmonary arterial pressure, which is in accordance with earlier findings (Eppinger, Burwell and Gross 1941; Cournand 1947; Dexter, Haynes, Burwell, Sosman and Evans 1947; Taylor, Pollack, Burchell, Clagett and Wood 1950; Storstein, Humerfelt, Muller and Rasmussen 1952; Hultgren et al. 1953). The size of the shunt was obtained from the numerical difference between pulmonary and systemic blood flows. In the presence of left to right shunt to the pulmonary artery the determination of the systemic flow is almost as reliable as in normal individuals - the only difference being that samples of mixed venous blood are obtained from the right atrium. The determination of the pulmonary blood flow, however, may be subject to wide variations. Here, mixed venous blood is obtained from the pulmonary artery. It is obvious that the degree of mixing will depend on the position of the catheter tip relative to the site of the ductus and the direction of the jet containing fully oxygenated blood. Consequently, although some eon- cept of the magnitude of the shunt may be gained from the present results, the pulmonary flow data have not been used for the calculation of vascular resistance.

It is noticeable that pulmonary hypertension does not necessarily develop despite longstanding increase in blood flow through the lungs. Moreover, in some patients exercise caused further rise in pulmonary blood flow without concomitant increase in pulmonary pressures. It is thereby implied that the pulmonary vascular resistance may fall further, either due to dilation of peripheral vessels or to opening up of new vascular pathways. In contrast, when pulmonary hypertension was present already at rest, exercise caused further rise in pulmonary pressures despite lower rates of pulmonary blood flow. The difference in pressure response to increased circulatory demand between these two groups becomes more evident during the exercise test. The presence of this ))reserve capacity)) of the pulmonary vasculature in the patients with normal pulmonary blood pressure may indicate that the natural prognosis of disease is favourable in these. Such concept cannot, however, be substantiated before follow up studies will be available.

It is evident from the above discussion that high pulmonary blood flow is often not associated with pressure increment in the pulmonary circuit. As a result other factors have been thought t o contribute to the pulmonary hypertension that is encountered in some patients. Change in the structural nature of the pulmonary arterioles such as medial hypertrophy and adventitial fibrosis have been described in these patients (Edwards, Douglas, Burchell and Christensen 1949). It has also been suggested that increased tone in the pulmonary vascular bed may be a contributing factor (Hultgren et al. 1953). Following ligation of the ductus pulmonary blood flow decreased with concomitant fall in pulmonary arterial pressure. While this pressure fall may be due to reduction in blood flow alone, i t is not evidence against the presence of increased vascular resistance at the time when the ductus is patent.

Pulmonary hypertension is often encountered as a complication to various


cardiopulmonary disorders. In essence two different types are found. One is mainly due to patho-anatomical change in the lung vessels and characterized by increased - often to excessive degrees - pulmonary arterial pressure, low pulmonary capillary venous pressure and decreased pulmonary blood flow. The prototype of this pattern is primary pulmonary hypertension (Werko and Eliasch 1952). In the other group the main cause is found in the left heart, either left myocardial failure or mechanical hindrance to flow as in valvular heart disease. Here, pulmonary hypertension does, generally, not reach those excessive degrees as in the former group. In contrast, however, the pulmonary capillary venous pressure is also increased, while the pulmonary blood flow may either be increased, normal or decreased. Finally, a third group can also be defined, i. e. where the moderate elevation of pulmonary pressures is associated with high pulmonary blood flow but with no evidence of secondary vascular change. This group is also characterized by low pulmonary capillary venous pressure.

Six of the seventeen patients in this series had increased pulmonary arterial blood pressure. The hemodynamic data obtained in two, Nos. 647 and 792 are strikingly similar to those in primary pulmonary hypertension, with excessively increased pulmonary arterial pressure, normal pulmonary capillary venous pressure and low pulmonary blood flow. The poor operative result in this category of patients stresses the importance of its recognition before operation is considered. In patient No. 647 blood was certainly shunted from the pulmonary artery to the aorta. Such reversal of the shunt has been repeatedly described and has caused much concern regarding therapy (Johnson et al. 1950; Burchell, Swan and Wood 1953; Dammann et al. 1953; Hultgren et al. 1953; Kattus and Muller 1953; Gordon et al. 1954). Ligation of the ductus results in increased blood flow to the lungs. Because of prevailing volume-pressure relationship of the pulmonary vascular bed pulmonary arterial pressure tends to increase further. Eventually the right ventricle cannot respond adequately to the increased burden and right heart failure develops. The pathoanatomical pictures of the lungs in these cases as in cases of ))primary)) pulmonary hypertension resemble each other by the marked decrease of the pulmonary vascular capacity. It has been suggested that this syndrome may develop slowly in patients with patent ductus arteriosus if not operated on. This is not supported by the findings in the present series, as these cases neither had the largest shunts, nor were amongst the oldest in the series. It is not improbable that such patients have had primary pulmonary hypertension associated with patent ductus arteriosus already from childhood.

In the four remaining cases of pulmonary hypertension the pressure in the pulmonary artery increased during exercise, but not to levels to cause reversal of shunt. Two of these, Nos. 288 and 588, had moderate increase in pulmonary capillary venous pressure, and thus correspond to the second type of pulmonary hypertension as outlined above. As the pulmonary blood flow = left ventricular output was relatively high, the increase in pulmonary capillary venous pressure may not be solely due to ventricular failure but also be regarded as a physiological means of maintaining the increased left ventricular work. After surgery pressures and flow normalized in these patients (fig. 2) - Patients Nos. 365 and 651 displayed


Pig. 2,

gram c is a ma

(PCV), Strips of simultaneous recordings of electrocardiogram, pulmonary capillary venous pressure pulmonary arterial pressure (PA) and brachial arterial pressure (BA) curves and phonocardio-

ibtained during heart catheterization at rest in patient No. 588/642 before and after surgery. There rked decrease in both pulmonary capillary venous and pulmonary arterial pressure after operatlun.

152 HARALD ELIASCH, KERSTIN ERTKSSON A N D LARS WERKO.

essentially the similar pattern apart from the pulmonary capillary pressure being normal and the pulmonary arterial pressure only slightly elevated. These two patients agree hemodynamically with the lastly defined group of pulmonary hypertension. Following operation the pulmonary arterial pressure returned to a normal level.

It is thus of utmost importance to differentiate between these types of pulmonary hypertension since the increase in pulmonary pressures in the last two groups indicates the need for surgery, in contrast to the first group where the pulmonary hypertension sather increases the risk of operation.

In the presence of the vascular connection between the aorta and the pulmonary artery it is natural that part of the left ventricular output must be directed to the pulmonary circuit due to its lower vascular resistance. As the pressure increases in the pulmonary artery the shunt is due to decrease. This leads to a decrease of the left ventricular output towards a normal level and also to a normalization of the left ventricular work. The patient, however, is not benefited by this, as symptoms will arise from pulmonary hypertension.

I n those patients having normal pulmonary pressure and who are essentially free of symptoms, the left ventricle performs increased work due to a large volume transported in contrast to patients with arterial hypertension where the increased work is due to a normal volume transported against increased vascular resistance. I n arterial hypertension the work performed increases during exercise due to increase in output. I n ductus arteriosus the systemic output has also to increase during exercise to meet the enhanced metabolic needs of the body. This does not necessarily have to be met with by further increase in the left ventricular output and work, since a decrease in the shunt would lead to an increased blood flow to the periphery. If such a mechanism would operate, exercise will thus reduce the circulatory abnormalities in this disease. The present data could in some patients favour such a concept, but no conclusions can be drawn due to the unreliability in determining the pulmonary blood flow.

The roentgenological heart volume was increased in the majority of patients, mostly due to lateral displacement of the left ventricular and pulmonary arterial contour. The heart volume was larger in the patients with pulmonary hypertension than in the others. There was, however, no correlation between the height of the pulmonary artery pressure and the heart size, nor between the pulmonary or systemic blood flow and the heart volume. There was a fair correlation between the heart volume and the total amount of hemoglobin. This is in accordance with the results of Kjellberg, Rudhe and Sjostrand (1949) in normal individuals. The lack of correlation between heart size and blood flow was also found by Warren, Elkin and Nickerson (1961) in patients with posttraumatic arterio-venous fistulas.

There was no regular increase in total hemoglobin in the present series. Except for the correlation t o the heart size, the amount of total hemoglobin did not correlate to any one factor. Of interest is that the amount of total hemoglobin was not larger in the patients with arterial unsaturation and did not correlate to increased pressures in the pulmonary circuit.

The behaviour of renal dynamics in patients with heart disease has been in-


creasingly studied during the last decade. Most results have been published from studies on patients with mitral stenosis or cardiovascular hypertensive disease. In mitral stenosis decrease of renal blood flow does not seem to be related to the presence or absence of right heart failure but more to the degree of pulmonary hypertension (Werko, Varnauskas, Eliasch, Ek, Bucht, Thomasson and Berg- strom 1954). It was thus of interest to ascertain whether the presence of patent ductus arteriosus caused a redistribution of the systemic blood flow with decreased renal perfusion. In the cases with normal blood pressures in the pulmonary circuit the renal blood flow was slightly diminished in three out of nine cases. The response to exercise varied with decrease of renal blood flow and sodium excretion in some and increase in some. The least alteration of renal blood flow seemed to occur in the case where exercise caused increased systemic blood flow without increase in left ventricular output.

In t,he patients with pulmonary hypertension the resting values for renal blood flow was lower, but the response to exercise varied. There was a slight correlation between the pressure in the pulmonary artery and the renal blood flow - similar to the correlation found in mitral stenosis. There was no correlation between the renal blood flow and the systemic or pulmonary blood flow or to the amount of total hemoglobin.

The results of the renal function studies thus indicate that the influence of the altered circulation in these cases is less than in patients with mitral stenosis, although the circulation may have been markedly altered for a long time. This again brings out the question whether rheumatic valvular disease in itself has influence on the hemodynamic reaction of the kidneys.

In some patients the renal blood flow increased to normal level after operation indicating the reversibility of the alteration. Similar results have been found in patients operated on for mitral stenosis (Werko, Bergstrom, Bucht, Ek, Eliasch, Eriksson, Thomasson and Varnauskas 1956) and coarctation of the aorta (Werko, Ek, Bucht and Karnell 1956).

As mentioned earlier it is generally believed that all patients with patent ductus arteriosus should be operated upon, preferably already in early childhood since the operative mortality is negligible in children with uncomplicated patent ductus. In the adult the mortality rate seems to be relatively small but becomes significant in patients suffering from pulmonary hypertension (Campbell 1955). It is a t present not possible to assess whether pulmonary hypertension will eventually develop or not in a young patient. In fig. 3 is demonstrated graphically the relationship between the age of the patient on the one hand and the pulmonary arterial pressure, pulmonary blood flow, roentgenological heart volume and renal plasma flow on the other in seventeen patients with patent ductus arteriosus. It is obvious that there is no correlation between age and severity of disease. This means that, as discussed before, the longstanding increase of pulmonary blood flow per se does not necessarily cause pulmonary hypertension and that the natural prognosis of disease may be favourable. Patients without or with only few symptoms were in majority in this material, which should be overweighted with those who are incapacitated, since they are more likely to be admitted for medical care. How-

154

12.

bloodflrm *' Pulm

HARALD ELIASCH, KERSTIN ERIKSSON AND LARS WERKO.

a a

I a I

Normal Pulm art.press. *' Elevated Pulm art. pres6.

Mean press 50-

0. m m b 25

% 8 i

X f e. f t

I I 1 I 1 I

Fig. 3. This graph shows the relationship between the age of the patient on the one hand, and the mean pulmonary arterial pressure (PA), the pulmonary blood flow, the roentgenological heart volume and the renal plasma flow (PAH) on the other in seventeen adult patients with patent ductus artcriosus. Dots denote patients with a mean pulmonary arterial pressure below, crosses above 25 mm of mercury.

ever, enough patients deteriorate significantly to suggest that operation should be performed when they are young. The overall decreased longevity of patients with patent ductus has been pointed out by Bullock, Jones and Dolley (1939) and Keys and Shapiro (1943). Moreover, the risk of complicating subacute bacterial endocarditis cannot be overlooked, even if the incidence of disease and therapeutic measures have changed considerably since the era of penicillin treatment.

Summary.

1. Clinical and physiologic studies were performed in seventeen patients with patent ductus arteriosus. Clinical investigation included electrocardiogram and


determination of the size of the heart by roentgen. Selective angiocardiography was performed in eight patients.

2. In all patients right heart catheterization was performed including measurements of pressures and flow in the pulmonary and systemic circuit. The renal clearance of para-amino-hippurate and inulin was determined simultaneously. I n nearly all patients cardiopulmonary and renal studies were carried out also during a graded exercise test.

3. Eleven patients had normal pulmonary pressures, associated with high pulmonary blood flow. They were essentially free of symptoms. The remaining six had varying degrees of pulmonary hypertension and were in general accordingly incapacitated. 4. There was no correlation between age and pulmonary arterial pressure level.

The oldest patient, 47 years of age, had normal pulmonary arterial pressure. Like- wise, age did not correlate to the size of the heart or the level of renal blood flow.

5. On effort pulmonary arterial pressure was unaltered in those patients having normal pulmonary pressure a t rest. I n those patients having pulmonary hypertension exercise generally caused further increase in pulmonary arterial pressure.

6. The systemic blood flow rose during exercise. Whether this was due to a reduced shunt or to an increase in left ventricular output could not be assessed because of the difficulties in determining the pulmonary blood flow accurately.

7. In patients with normal pulmonary pressure the renal blood flow was either normal or slightly reduced. I n pulmonary hypertension the renal blood flow was generally significantly decreased.

8. Five of those eleven patients having normal pulmonary arterial pressure were operated upon. Surgery and immediate postoperative course was uneventful in all. I n one patient, however, the continuous murmur reappeared six weeks after operation. Follow up catheterization study disclosed reopening of the ductus.

9. All six patients who had pulmonary hypertension were operated upon. In one the immediate postoperative course was uneventful and associated with a reduction of pulmonary arterial pressure to normal level. I n three other patients pulmonary hypertension was also completely relieved; one of these was discharged with residual symptoms from arterial embolism, the second patient with paraplegia and in the third patient reactivation of rheumatic endomyocarditis occurred. This patient eventually recovered and was discharged six months after surgery in good condition.

10. The importance of differentiating between so called secondary and primary pulmonary hypertension in the patients is stressed. A marked reduction of pulmonary pressures was obtained postoperatively in the former group. I n the latter group of two patients the operative result was poor. I n the one patient who had reversal of shunt with marked cyanosis, the ductus was by purpose only partidly closed. She did not improve after operation. The other patient died during surgery.

11. It is inferred that increased pulmonary blood flow alone is not responsible for the development of pulmonary hypertension. The possible r81e played by anatomical narrowing and increased vascular tone in the peripheral pulmonary vessels is discussed.


Acknowledgements.

Prof. C. Crafoord, Drs. V. Bjork and A. Senning performed the surgery in the present material. Drs. H. Bucht and J. Ek assisted in the performance of the renal studies. Drs. G. Jonsson, S. R. Kjellberg and U. Rudhe made the angiocardiographic and electrokymographic examinations. Dr. T. Sjostrand performed the studies on lung function and total hemoglobin. All are thanked for valuable cooperation.

References.

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