THE PATENCY OF THE SO-CALLED “ANATOMICALLY OPEN

BUT FUNCTIONALLY CLOSED” FORAMEN OVALE”

PSUL GROSS, M.D. CLEVELAND, OHIO

z

AH?? and M6nckeberg2 indicate that under certain conditions the so-called “anatomically open but functionally closed” foramen

ovale may become patent and lead to paradoxical embolism. Other re- ports in the literature add support to this contention, including the more recent publications of Beattie and of Freneh,4 which give autopsy find- ings of emboli caught in the foramina ovale. It has been claimed that when the right auricular pressure exceeds the left auricular pressure, the functionally closed foramen becomes patent. Because this type of fora- men ovale has not been universally recognized as a factor in the produc- tion of paradoxical embolism, the present study of the behavior of the foramen ovale under various differences in auricular pressures was undertaken.

METHOD

The intcrauricular septum of hearts with opcu, valvelike foramina owle, removd

at autopsy, is clamped by means of four screws between two flanged metal plates

that have a circular opening completely exposing both sides of the foramen ovalo. (Fig. 1.) Two glass cups (C) with three side openings are cemented to the flanges and function as artificial atria. Instead of blood, a fluid is used which consists of 0.32 per cent tragacanth suspended in 0.9 per cent saline. The viscosity and the osmotic pressure of this suspension are approximately that of blood. The height of

the reservoirs (R) holding this fluid determines the auricular pressure which is measured by a straight manometer tube (M) connected with the artificial atrium by

means of the middle side tube. The second side tube connects with the reservoir. The third side tube is clamped off and serves as a vent for the escape of air caught in the apparatus. Artificial eniboli are prepared by mixing “Pates”t (a coc

centrated form of Latex) with plaster of Paris in a proportion so that the small pieces (1 x 1 x 2 mm. to 3 x 2 x 3 mm.) just about sink in the fluid. The mixture con- sists of 3.2 gm. Yatex and 1 gm. plaster of Paris. Thrsc pieces, ten to tweuty

in number, are introduced into the right atrium. Before each experiment the ap- paratus is tested for leakage, under a pressure of 300 mm. of fluid.

During the course of the cxpcrimcnt the height of the right reservoir is in- creased on several occasions so that various degrees of predominance in right auricular pressure are obtained. Due to the higher level of fluid in the right reservoir, a flow of the fluid is established through the foramen ovale from the right into the left reservoir. The heights of the fluid level in the reservoirs are recorded at, thr start and after one minute of flow. The auricular pressures as shown by the ulnnometcr in millimeters of fluid arca also rccordrd at thr start of the

*From the Leboratory of Charity Hospital and the Institute of Pathology, West~?m Reserve TJniversity, CleVel%nd. Ohio.

tI<lentz R- Co., G. M. E. H., Thomas Haus. Schogenstehl 7. Hamburg I, Germany.

101

1.02 THE A1\IERI(.!AN HEART JOlJRISAI,

flow and during the flow. The change in volume in either reservoir during this time

indicates the flow in one minute through the foramen ovalc. Similar observations

are made when the lrrel of the left reservoir ia raised higher than that of the right

SO that there is a predominance of pressure in the left atrium. During a period of

flow under a maximum predominsnw of right auricwlnr lneswre the apparatus is

shaken with both hands to agitate the artiticial emboli in the right auricle. At the

end of one minute of such flo\v, the emboli in the left auricle as well as the emholi

caught in the foramen are counted.

Fluid consists of 0.32% c+tm tragecanth in 0.9% saline.

Fig. L-Diagram of aPPaI%tus.

With the fluid level of the right. reservoir higher than that of the left reservoir and the tubing connecting with the left reservoir pinched off, the left auricular pressure may be equal to the right auricular pressure or may even exceed it.. This paradoxical condition is explained by the fact that the foramen ovale behaves as a valve and transmits pressure freely in one direction only. As soon as the tubing to the left reservoir is opened, a drop in both auricular pressures occurs. This drop is greater on the left side. As the flow is maintained, the left auricular pressure begins to rise slowly while the right auricular pressure falls slowly. However, during the minute of flow, the right auricular pres-

GROSS : PATENCY OF FORANEPI; OVAIZ 103

sure is always greater than that, of the left. When, at, the end of one minute, the tubing to the left reservoir is again pinched off, bot,h auricu- lar pressures rise to a level commensurate with the fluid level in the right reservoir ; and again the left auricular pressure may rise to a slightly higher level than the right because of the valvelike action in the foramen ovale. The fluid level of the right reservoir descends, while that of the left reservoir rises correspondingly from the time that the tubing to the left reservoir is opened to the moment that it is pinched

cc.

0 20 60 100 200 300 400 Initial difference in reservoir pressure in tn?of flu$’

l Flow from riqht to left atrium @Artifact due to sweltity x ,, 17 left 1’ ricjk 99 @Ferforation of septum prirnum

Fig. Z.-Graph showing relationship between the difference in reservoir pressure and the flow through the foramen ovale.

off again. The volume of flow from right to left increases with the degree of preponderance of right auricular pressure. The results of ex- periments performed on sixteen patent foramina ovale are listed in Table I. The graphical representation of the relationship between the leakage through t.he foramen ovale and the difference in reservoir pres- sure is shown in Fig. 2. It is seen that an almost linear relationship is indicated.

1 I

OF

FORA

MEN

- IN

ITIA

L

CIRC

UMFE

RENC

E PR

EDO

MIN

AKCE

mm

. 30

'hree

sm

all

opcn

- in

gs

1-2

mm

. in

di

amet

er

25

40

25

16

24

IN

RIG

HT

RESE

RVO

IR

PRES

SITR

E

mm

. 42

5 31

0 21

0 15

5 49

3 33

9 20

2 97

426

534

195 79

43

6 31

6 21

1 81

452

281

221 55

463

337 99

446

336 99

462

305

219 74

TERM

INAL

PR

EDO

MIN

ANCE

IN

RIG

HT

RESE

RVO

IR

PRES

SURE

mm

. 26

5 18

5 10

5 70

292

205

121 9

318

381

143 59

300

329

148 60

29

0 16

5 13

7 33

312

228 71

32

6 24

8 75

362

235

166 40

-.

-

RIG

HT

/ LE

FT

RIG

HT

1 LE

FT

RIG

HT

LEFT

580

605

619

619

361

361

51

51

592

592

635

634

366

366

600

600

583

584

581

582

358

358

587

585

435

395

193

103

500

465

357

357

285

273

340

340

600

605

600

602

595

600

383

383

402

402

270

270

569

569

339

339

414

412

258

258

540

540

227

227

318

318

192

192

510

511

531

530

547

548

575

586

600

600

545

545

354

354

515

515

440

455

29;

570

363

424

243

544

390

425

283

550

440

485

565

461

460

530

842

455

266

532

360

340

263

557

325

395

233

535

375

415

268

530

367

430

548

319

387

507

273

352

216

517

553

553

490

490

330

330

552

552

1 Y

I’L‘I

AL

AURI

CULA

R

PRES

SURE

S I: \I*R

II’ULA

R PR

ESSU

RES

DllR

ING

FLO

W

TERM

INAL

AU

RICU

LAR

PRES

SURE

S

i 2 FI

,O\V

IN O

NE

.\I IX

UTE

C.C.

59

0

500

430

; 35

0 ;

GO

0 z L’.

500

k 31

0 P

64

z 42

0 2

550

* Z 01

0 80

F .5

45

F 38

0 z 4

260

& 80

t:

040

.*

z 44

0 z

330

> r 80

57

0 43

0 12

0 47

.5

320 70

395

760

192 40

TABL

E I--

CONT

’D

NO. 9 10

11

12

13

14

15

16

OF

FORA

VEN s “9

'3

113

CIR(

‘UIlF

EREN

CE

I-

INIT

IAL

PRED

OM

INAN

CE

IN

RIG

HT

RESE

RVO

IR

PRES

SURE

mm

. 41

3 33

2 16

8 87

439

294

210 60

46

0 32

0 20

5 65

425

340

133 47

410

290 96

42

9 29

3 54

479

337 43

474

335

131

mm

. 30

4 24

5 12

8 67

352

235

157 48

228

23s

127 40

33

2 27

8 92

42

366

273 87

34

7 19

6 40

386

271 34

36

0 24

8 92

~___

TERM

INAL

PR

EDO

MIN

ANCE

IN

RIQ

HT

RESE

RVO

IR

PRES

SURE

I- I -- -

ISIT

I.ZI,

AURI

CULA

R

PRES

SURE

S

RIG

HT

589 588

360

586

558

556

327

560

528

278

482

568

145

226

496

450

572

558

580

656

560

559

606

608

543

605

590

606

LEFT

R

IGH

T

589

448

590

474

360

300

590

555

558

385

556

438

327

240

560

540

,528

43

2 27

8 45

4 48

2 52

5 56

8 55

5 14

5 45

0 22

6 48

2 49

4 57

8 44

6 55

7 56

3 55

4 55

2 49

2 56

8 57

6 64

8 36

6 67

0 41

6 56

8 53

5 57

7 45

4 57

7 49

7 53

0 53

5 60

4 40

0 6O

G

453

625

551

-

1 LUR

ICUL

AR

PRES

SURE

S

DURI

NG

FLO

W

- I LE

FT

376

417

272

546

352

418

228

530

365

426

487

545

124

274

507

498

213 274

512

313 38s

.533

24

7 33

8 49

0 28

5 37

8 54

3

TERB

CINA

L AU

RICU

LAR

FLO

W

IN

PRES

SURE

S O

NE

XINU

TE

RIG

RT

~-~

542

548

340

578

514

524

304

556

507

244

425

508

187

252

525

556

523

586

LEFT

542

548

340

582

514

524

304

556

507

244

425

508

187

552

510

548

510

568

C.C.

42

0 LI

32

0 z

190 90

-z

.

410 250

T > 17

0 +

50

x 58

0 5

380

-: 30

0 c 7

160

370

3 22

0 2 :,

105

9 40

z

130

7.

90

= 2.5

2 r-

590

r: 32

5

306 THE AJIERICAK IWART JOITRNAI>

Occasionally emboli l)ass sl~ontaneously through t.lie foramen ovalc, hut. generally emboli pass through the foramen ovale or are caught in it only after the apparat,us has been shaken vigorously and the emboli thereby set into motion. Table II shows the relationship between the circumference of: the foramen, the preponderance of the right auricular pressure, the preponderance ot’ the right reservoir pressure, and the number of emboli which passed through, or were caught in the foramen ovale. No determination of the transmission of emboli was made on heart numbers 1 and 3. The only foramen ovale of those investigated which did not allow emboli t,o pass int,o or through it was number 13. The probable explanation for the behavior of this Porameu is to be found in its small size.

NO.

2 4 5 5 5 6 7 8 9 9

10 11 12 13 J4 l:? 1 (i

PREDOM- PREDOM-

CIRCUM- INANCE OF INANCE OF FERENCE OF

FORAMEN ’ RIGHT ~ RIGHT

RESERVOIR AURICULAR

PRESSURE PRESSURE

32 , 680 230 25 40 40 40 25 16 24 22 22 28 40 12

8 28 2:: 23

437 - 281 ( 10 221 15 452 15 456 103 447 474 332 413 1 60

72 439 33 460 ' 67 425 326 410 342 429 A3 479 lt50 510

NUMBER OF

NUMBER OF EMBOLI

EMBOLI WHICH

CAUGHT IN PASSED FORAMEN , THROUGH THE

FORAMEN

0

0

3 0 0 2 1 2 2, 3 0 0 5 4 4

When the predominance of pressure is shifted to the left side and the tube communicatin, v with the right reservoir is pinched off, the right auricular pressure may correspond to the right reservoir pressure, or it may be higher. When the tubin g to the right reservoir is opened, the right auricular pressure drops according to the fluid level of the right reservoir. In a few foramina ovale no subsequent increase in right auricular pressure occurs; nor is there a change in fluid level in either reservoir. In other words, some patent foramina ovale allow no leakage of pressure or fluid from left to right.. In the larger number of cases, on releasing the pinched-off tubing, there is an immediate rapid drop of right auricular pressure to a level commensurat,e with the right reservoir fluid level. This is followed by a slight gradual rise in right auricular pressure accompanied by a slight drop in the fluid level of the left

GROSS : PATENCY OF FOKAhfEN OPALE 107

reservoir and a coincidental rise in fluid level of the right reservoir. The greater the predominance of left auricular pressure, the greater the a,mount of leakage through the foramen ovale. JVith the exception of two instances, the amount of flow t,hrough the foramen ovale from left

to right is slight compared with the flow from right to left at similar

differences in pressure. The two discrepancies where considerable leak-

TABLE III

_____

NO.

1 2 3

4 5 G 7 8 9

10 11 1 &' 1.7 14 : 28 1.5 23 16 33

30

32 Three small

openings l-2 mm.

25 40 25 16 24 32 2x 40 13

x

CIRCUM-

FERENCE OF

FORAMEN

- PREDOM-

INANCE OF

LEFT

RESERVOIR PRESSURE

445 500 474

423 561 470 529 450 406 380 460 425 410 442 476 440

AURICULAR PRESSURE DUR-

ING FLOW

RIGHT i LEFT

No change No change

115 1 569

290 465 53 550

156 582 173 571

46 592 275 486 - -- / XI

No change No change

163 506 133 603 155 I 555

-

FLOW IN ONE MINUTE

355 162

83 58 10 90 40 50

n 0

G6 0

50

ape occurred from left to right are explained in one by a perforation in the septum, and in the other by a severe distortion of the foramen from edema secondary to clamping. The results of these investigations are

tabulated in Table III and indicated in Fig. 2.

COMMEiW

The results obtained indicate that t,he so-called anatomically patent, functionally closed foramen ovale transmits pressure, fluid, and sus-

pended solids from the right to the left atrium when the right auricular pressure exceeds that of the left. These findings are in accord with the observations and conclusions of Zahn,’ 316nckeberp;’ l>,eattie,3 French,” (‘hiari,j and others.

Zahn collected 139 cases which at autolq- had a patent foramen ovale. Among these cases, he found two with thromhotic occlusion of the fora- men and seven with paradoxical embolism. In addition, he listed a third case, referred to him, of thrombotic occlusion of the foramen ovale. Zahn believed the explanation of paradoxi& embolism to lie in the fact

108 THE AMERICAK HEART JOURNAL

that in congestive heart failure there is an elevation in right auricular pressure with a coincidental reduction in left auricular pressure. In all nine cases, evidence of venous stasis conditioned by chronic bronchitis, pulmonary emphysema, edema, atelectasis, tuberculosis or pleuritis was found. The anatomical evidence pointing to a previously existing con- gestion and elevation of pressure in the right heart consisted of dilata- tion and hypertrophy of the right auricle and ventricfe, the enlargement of the fossa ovalis and the bulging of its wall to the left.

Beattie reported a case of pulmonary embolism which, at autopsy, showed occlusion of the pulmonary artery by an embolus and a second emholus caught in the foramen ovale. This foramen ovale was of the type considered anatomically open but functionally closed. Beattie in- ferred that the embolic occlusion of the pulmonary artery preceded the embolic occlusion of the foramen ovale. He contended that the embolic occlusion of the pulmonary art.ery caused an elevation of the right auric- ular pressure and a coincidental fall in the left auricular pressure which forced the foramen ovale open and allowed the second embolus to slip in and lodge there. He indicated that in all probability the reason for the patient’s survival for a short time after the pulmonary occlusion was the patent foramen ovale which allowed the blood to be shunted across to the left atrium. Hc suggested that patency of the foramen ovale be kept in mind to explain similar short survivals following pul-

monary occlusion.

The apparatus used in t.hese investigations does not reproduce the rapid movement of fluid with eddies which are present in the living heart. It is therefore necessary to agitate by shaking, but this also ap- pears inadequate. It is possible that with a modification of the appa- ratus to provide for a brisk flow of the fluid with a production of eddies, a larger number of emboli would pass through the foramen ovale under the same pressure conditions.

A valvelike action of the foramen ovale is established by its capacity, in some cases, to prevent completely the leakage of pressure and fluid from left to right, and in other instances to transmit comparatively very little fluid to the right atrium. This valvelike action is due to the tenuitp and pliancy of the septum primum and the relative thickness and rigidity of the septum secundum.

There are no data available on human left and right auricular pres- sures, and the pressures used in these experiments may very well be beyond the pathological limits occurring in man. Nevertheless, the be- havior of this type, of- foramen ovale under these experimental condi- tions is probably a good indication of the behavior cIinically under cer- tain pathological conditions.

GROSS : PATENCY OF FOKA1IEX OVAIX 3.09

CONCLUSIONS

These investigations on the so-called anatomically open but func- tionally closed foramen ovale furnish experimental proof for the follow- ing statements :

1. TJnder conditions of preponderance of pressure in the right atrium over the left, pressure, fluid, and emboli may be transmitted from the right atrium through the foramen ovale into the left atrium.

2. When the left auricular pressure is greater than the right, com- paratively little or no transmission of pressure or fluid from the left atrium to the right atrium occurs due to a valvelike action of the fora- men ovale.

The author thanks Dr. H. S. Reichle and Dr. Morris Simon for aid in securing material.

REFERENCES

1. Zahn, F. W.: Ueber paradoxo Embolie und ihre Bedeutung fiir die Geschwulst- metastase, Virchows Arch. f. path. Anat. 115: 71, 1889.

2. MGnckeberg, J. G.: Herz und Gefbse. Handbuch der speziellen pathologischen Anatomie und Histologie, by Henkc, F., and Lubarsch, O., Berlin 2: 46, 1924, Julius Springer.

3. Beattie, W. W.: Paradoxical Embolism Associated With Two Types of Patent Foremen Ovale, Internat. A. M. lMuseums Bull. 11: 64, 1925.

4. French, L. R.: Cardiac Paradoxical Embolus, Arch. Path. 11: 383, 1931. 5. Chiari, H.: Personal communication to the author.