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STUDIES OF BLOODVOLUMEIN THE TETRALOGYOF FALLOTAND IN OTHERTYPES OF CONGENITALHEARTDISEASE1

BY WOODROWNELSON, H. S. MAYERSON,JOHNH. CLARK, ANDCHAMPLYONS

(From the Departments of Physiology and Surgery, School of Medicine, Tulane University ofLouisiana, New Orleans)

(Received for publication January 20, 1947)

The recent introduction by Blalock (1) of anoperative procedure for the successful treatment ofthe tetralogy of Fallot has focused considerable at-tention on the various manifestations of this con-dition. It has also indicated the need of more in-formation to aid in the diagnosis and prognosis, aswell as in the preoperative and postoperative treat-ment of the patients with this disease. The pres-ent study is concerned particularly with the meas-urement of blood volume, hemoglobin, and plasmaprotein in 7 cases of tetralogy of Fallot, 4 cases ofisolated septal defect, and 1 case each of Eisen-menger complex, isolated pulmonic stenosis, co-arctation of the aorta, congenital mitral stenosis,and patent ductus arteriosus.

Fallot (2), in 1888, described the complex ofcombined congenital cardiac defects of pulmonicstenosis, right ventricular hypertrophy, patent in-terventricular septal defects, and dextroposition ofthe aorta which is commonly referred to as the"Tetralogy of Fallot." It is a common congenitaldefect of the heart. It constitutes 77 per cent ofthe 110 cases of pulmonary stenosis and 66 percent of 40 cases of pulmonary atresia in Abbott's(3) series of 1,000 cases. The Eisenmenger com-plex is much less common. It differs from Fal-lot's tetralogy by having no pulmonary stenosisor atresia. The prognosis is somewhat better, theaverage life span being 16 years compared to 12.5years in Fallot's type (4). The oldest age of sur-vival recorded in either type is 60 years (5).

The principal extracardiac pathology of Fallot'stetralogy is a generalized vascular distention, cap-illary hyperplasia (3), and increased tortuosity.This is accompanied by polycythemia and in-creased blood viscosity. Blood arteriovenous-oxy-gen difference is increased, and its per cent oxygen

1One of series of studies being conducted under agrant from the Research and Development Division,Office of the Surgeon General, United States Army.

saturation is decreased. Cyanosis, usually presentat rest, is increased on exertion, when dyspnea alsoappears. 4

Although the elevated values of hemoglobin andhematocrit in the tetralogy of Fallot suggest an in-creased blood volume, measurements of blood vol-ume have been recorded in relatively few cases ofthis disease. Meyer (6) measured the volume in1 case using congo red, as did Blumenfeldt andWollheim (7) using trypan blue. Both authors re-ported extremely low values for plasma volumes.Weber and Dorner (8), using the carbon monox-ide method, obtained a value of 131 ml. per kgm. ora total blood volume of 6,040 ml. in a patient withcyanotic congenital heart disease (morbus caeru-leus) as compared with the value of 77 ml. perkgm. in normal individuals measured by theirmethod. Hallock (9) used the T-1824 blue dyein studying 2 cases. He found low plasma volumes(29.9 and 29.3 ml. per kgm.) and high cell vol-umes (144 and 77 ml. per kgm.).

METHODSANDPROCEDURE

Considerable care was devoted to the standardization ofthe procedures and methods used. All patients werestudied under basal conditions. Breakfast was omitted,and the patients rested quietly in the recumbent positionfor at least 10 minutes before the determinations weremade. Blood was drawn from an antecubital vein intosyringes coated with a thin film of heparin. Total cir-culating plasma volume was determined by the method ofGregersen (10) using the Klett-Summerson photoelectriccalorimeter. The amount of heparin which was used didnot interfere with accurate determination of the plasmavolume. To rule out the question of possible inadequatemixing because of slowed circulation, several successivesamples were taken at 5-minute intervals after the usual10-minute sample. In a number of cases, simultaneoussamples were taken from the dorsal foot vein and anantecubital vein. All of our cases showed complete mix-ing in 1o minutes, and there was no evidence that thedisappearance curve of the dye differed from that given for"normal" individuals. All adults were injected with 5

860

BLOODVOLUMEIN CONGENITAL HEART DISEASE

ml. of dye. Children were given a smaller amount ofdye roughly proportional to their normal weight.

Hematocrit values were obtained by centrifuging bloodin Wintrobe tubes. Since spinning for 30 minutes at3,000 revolutions per minute gave the same results asspinning for an hour, the former interval was used inall of the experiments. Hematocrit determinations weremade on the samples of blood taken before and after theinjection of the dye. This served as a check on possiblefluid shifts during the 10-minute intervening period.

Red cell volumes were calculated from the hematocritvalues. The absolute accuracy of this procedure hasbeen questioned by some (11) and affirmed by others(12). The suggested discrepancy between the true redcell volume and that calculated from the hematocrit, ifpresent, would tend to make our absolute values uni-formly too high by a maximum of about 25 per cent . Itwould have less bearing on the relationship of the actualvalues to standard values obtained by the same procedure.

Hemoglobin was determined as oxyhemoglobin, usingthe photoelectric colorimetric method of Evelyn (13).Oxygen capacity determination by the Van Slyke-Neillmethod furnished the necessary constants for calculationof the actual values. Specific gravity of the plasma wasdetermined by the falling-drop method (14), and plasmaprotein levels were calculated from these values by theformula of Weech, Reeves, and Goettsch (15). All read-ings were made as soon as possible after the blood wasdrawn. A series of determinations made at intervals on9 "normal" subjects over a period of 4 months showedfluctuations of not more than 10 per cent. Changes ofgreater magnitude have therefore been considered assignificant.

The values given by Gregersen (10) were used to as-sign standard levels in the adult patients for blood volume,plasma volume, red cell volume, total plasma protein, andtotal circulating hemoglobin. These values were as-sembled by Gregersen from a large series and agree in

TABLE I

Tetralogy of Fallot

Patient Age Obs. Date Hct. Hb. Hb Plasma Plasma Plasma Red cell Bloodnumber wt. 1946 . . . protein protein volume volume |volume Comments

--I 1- -r

12 pounds under averageweight

Blalock procedure7-30-46

Died 8-1-4627 pounds under usual weightDied 4-9-46. Autopsy

18 pounds under usual weightNeoplastic cachexia develop-

ing symptom from carci-noma of stomach

Died 7-31-46. Autopsy

15 pounds under averageweight with marked mentaldeficiency

15 pounds under averageweight

Blalock procedure7-20-46

ml. per kgm

204

208

207

205

206

212

211

19 mos.

22 yrs.

20 yks.

4 yrs.

44 yrs.

6 yrs.

6 yrs.

kgm.

6.8

57.6

57.6

54.9

57.6

57.6

58.1

57.6

49.0

15.9

18.1

46.3

44.5

44.5

13.7

13.7

14.1

14.1

14.1

14.1

14.1

percent

60

76

70

68

59

64

66

70

70

75

70

66

65

63

81

81

73

74

62

59

61

7-9

1-31

2-12

3-12

3-26

5-9

7-18

7-29

3-28

4-30

7-29

5-7

6-18

7-5

7-29

8-15

6-20

6-29

8-7

8-15

9-10

gramspercent14.3

19.7

20.7

20.2

17.2

16.6

20

20.3

19.8

19.5

20.5

19.6

19.6

18.5

20.5

21.8

21.4

20.1

16.2

17.3

19.2

gramsper

kgm.28.7

51.5

40.0

32.0

18.9

24.9

25.3

23.2

33.6

45.8

21.9

31.0

33.5

24.5

63.1

93.4

44.9

52.6

24.8

17.8

22.1

gramspercent

6.09

8.05

6.85

6.85

5.88

6.99

7.06

6.68

7.34

7.69

6.99

5.81

5.39

6.37

6.41

6.16

6.65

7.30

7.09

4.80

6.9

gramsper

kgm.4.9

*5.14.0

3.3

2.6

3.3

3.0

2.3

4.0

4.0

2.4

3.1

3.2

3.1

3.7

5.0

3.8

5.0

4.1

2.0

3.1

80.3

64.1

57.8

48.5

44.8

54.0

43.0

34.3

54.0

51.4

32.0.

54.0

59.8

49.0

58.4

81.4

56.7

68.1

58.2

42.1

44.8

120.5

195.6

135.1

109.8

64.6

95.9

83.5

80.0

126.0

154.1

74.9

104.9

111.0

83.4

294.3

346.9

153.2

193.6

94.9

60.4

70.1

201.7

259.7

193.1

158.3

109.5

149.9

126.5

114.3

180.0

205.7

106.9

158.9

170.8

123.4

307.7

428.3

209.9

261.7

153.2

102.8

115.0

861

W. NELSON, H. S. MAYERSON, J. H. CLARK, AND C. LYONS

general with our findings and with those of other series(16). Standard values for blood, plasma, and red cell vol-umes in the children were calculated from the data givenby Brines, Gibson, and Kunkel (17). Wintrobe's stand-ard values were used for hemoglobin and hematocrit (18).Since all of our children were over 18 months old, theirstandard plasma protein level was assumed to be similarto that of the adult, i.e., 6.5 grams per cent.

Diagnosis of tetralogy of Fallot was made principallyon a basis of: (1) a history of cyanosis since, or shortlyafter, birth; (2) physical findings of a pulmonic stenosis-type murmur, cyanosis, finger and toe clubbing, andwatchcrystal nail changes; and (3) X-ray findings of de-creased conus pulmonus prominence. Retarded physicaldevelopment was prominent in all of the children studied,and retarded mental development was observed in 1 case.

Associated congenital defects were noted in 1 case. Restcyanosis was present to a greater or lesser degree in allcases, and its presence in the absence of dyspnea andtachycardia was striking. Congestive failure was foundin only 1 case (No. 206), and only 1 case (No. 212)showed marked cardiac enlargement. Right axis deviationwas consistently found electrocardiographically. Circula-tion times, intracardiac diodrast studies, and oxygen

analyses were done on some of the cases and showed mark-edly reduced arm-to-tongue or -face circulation time, rightventricle retention and right-to-left heart shunt, and de-creased arterial oxygen saturation and increased arterio-venous oxygen difference. The aortic arch was on the

left side in all cases. Two of the cases (Nos. 206 and 207)came to autopsy and presented the typical picture of thetetralogy of Fallot.

Case No. 210 was classified as an example of theEisenmenger complex mainly on the basis of a prominentconus, lack of aortic prominence, and lack of a murmurtypical of pulmonic stenosis. Since it was not feasibleto employ venous catheterization, the possibility of an iso-lated inter-arterial septal defect was not definitely ex-

cluded. This patient manifested cyanosis only on ex-ertion. The patient with isolated pulmonic stenosisshowed a markedly prolonged retention of diodrast inthe right ventricle and no evidence of septal defect. Thediagnosis of patent interventricular septal defect wasbased primarily on the history and character of themurmur.

RESULTS

A total of 22 sets of determinations was done inthe 7 cases of tetralogy of Fallot, 2 sets of determi-nations each in the case of the Eisenmenger com-

plex and in the case of coarctation of the aorta.Single sets of determinations only were obtainedin the cases of septal defect, congenital mitralstenosis, patent ductus arteriosus, and in isolatedpulmonic stenosis.

TABLE II

Miscellaneous Congenital Heart Disease

No. Diagnosis Ag e Hct. Hb. Plasma Plasma Plasma Cell Blood CommentsNo. wt. 1~~~~946 gloi protein protein volume volume volume

per grams grams grams gramskgm. cent ml.per per per per kgm.Cet100 mi. kgm. cent kgm.209 Isolated pul- 22 yrs. 57.7 5-21 62 18.0 20.9 6.40 2.8 44.1 72.0 115.9

monic stenosis

210 Eisenmenger 16 yrs. 47.6 5-31 49 14.9 12.6 7.65 3.86 50.4 48.4 98.8complex

214 Coarctation of 20 yrs. 47.2 6-6 44 13.1 11.1 7.27 3.43 47.4 37.2 84.5aorta

47.2 6-20 38 11.6 9.4 6.68 3.37 50.4 39.0 81.4Underweight

213 Patent ductus 9 yrs. 20.0 7-27 38 13.3 14.5 7.44 5.95 729.8 48.8 128.5 No cardiac de-arteriosus composition

215 Congenital mi- 22 mos. 10.4 8-13 37 11.0 19.0 6.68 7.31 109.0 63.9 172.7 In congestivetral stenosis failure

220 I.V. septal 5 yrs. 18.1 9-26 39 12.4 11.2 6.58 3.59 54.9 35.1 89.9defect




862


107

; B Plasma wVlLme* CeLl voLume

259h'37

18Q16917

1.31120 MI12. 14LOPta

85

iStandcrd Tetraq~lc Probable Coarctidton Patento0 Fatk* Eer oAOrta iCLusAve 21 Comply Ave. Arterious

dtrrrnrations cietcrrrnabonah

CoraenttaMitral

6tenosLs

Isolated T5olatedPlmonXc Septal

Stenosms DeFectAve 4deterrunabow

FIG. 1. COMPARISONOF TETRALOGYOF FALLOT WITH OTHERTYPES OF CONGENITALHEARTDISEASE

The results are given in detail in Tables I and II.A comparison of the plasma and red cell volumesin the various conditions is given in Figure 1.Our findings, contrary to those of previous in-vestigators, indicate that the plasma volume is notsignificantly or consistently reduced in the tetral-ogy of Fallot.

The highest value for the total blood volume was14,900 ml. (259 ml. per kgm.) found in the first

N30o

o ex

A

490

147mgloI-

5tanrard,

determination in Case 208. To our knowledge,this is the largest blood volume reported in thisdisease, although Hallock (9) reported a case ofpolycythemia vera with a blood volume of over 18liters. This case (No. 208) is of additional in-terest because of the dramatic response to bedrest, the blood volume dropping progressively fromover 14,900 ml. to 6,300 ml. in a period of 2months (Figure 2). This occurred without any

Tetralo~ oF ballotpatient RP yrs tM.W Bladock procedure

Died 8/1/46

358

2-12

la1 Plaearn voLuumeU CeLl voLume

274

t l!~~~~40

161~ ~ ~ ~ ~~

110 1410 2

O-1.2 3-26

DAT519465-9 7-18 7-29

FIG. 2. SERIAL DETERMINATIONSOF PLASMAAND CELL VOLUMESIN A PATIENT 22 YEARSOF AGE (M. W.) WITHTETRALOGYOF FALLOT

HI

-~~~~~~~~~~~~~~~~ ML-

ONA- -4 a-- - r -

863

le


hemorrhage and without clinical evidence of he-molysis. This decrease, while primarily due to adrop in the red cell volume, was accompanied by adrop in the plasma volume and total protein. Thissame tendency is also seen in Case 205, althoughthe number of observations in this case is limited.

The highest total blood volume per kilogramwas seen in Case 212. This child showed the mostsevere clinical picture of those surviving in thegroup. He manifested maximum cyanosis, ex-ertional dyspnea, and cardiac enlargement. Hisinitial blood volume was 4,215 ml. (307.7 ml. perkgm.), and a second determination some 2 weekslater showed a value of 5,268 ml. (428. 3 ml. perkgm.).

Initial values for plasma volume ranged from51.4 to 80.3 ml. per kgm. These are 20 to 92 percent above standard level as based on the patient'sobserved weights. Five of the patients were under-weight at the time they were studied. We havefound that in such individuals, plasma and cell vol-umes are more accurately predictable on the basis

Tet raioa

of optimal or usual weight. When the initialplasma volumes are calculated on this basis, thevalues in 4 of the 7 cases are almost exactly equalto the predicted or standard values. The remain-ing 3 cases (Nos. 204, 205, and 208) show values111, 121, and 147 per cent, respectively, of thepredicted levels. On the other hand, all of thepatients showed strikingly increased cell volumeswhich varied from 104.9 to 294.3 ml. per kgm.These values are from 269 to 998 per cent ofstandard on an observed weight, and 220 to 639per cent on an optimal or usual weight basis.Calculation of the total circulating hemoglobin re-vealed high values consistent with the elevatedtotal cell volume. The initial values varied from28.7 grams per kgm. to 63.1 grams per kgm. andrepresented levels which were from 242 to 764 percent of the standard on an observed, and 208 to 527per cent on an optimal or usual, weight basis.

Two of the cases of tetralogy (Nos. 208 and211) were operated upon (see case reports). Case208 survived only 3 days, while Case 211 has

of faliot02 Patient GLJears A.C

CT PildsmlvolumeCell volumw

6-E20 6-29 8-7OATC X946

FIG. 3. SERIAL DETERMINATIONSOF PLASMAAND CELL VOLUMESIN A PATIENT 6 YEARS Of

AGE (M. C.) WITH TETRALOGYOF FALLOT

864

cI


shown definite improvement. Determinationsmade postoperatively in Case 211 showed a pro-gressive decline in the total red cell volumes. Thetotal blood volume 1 month after operation wasonly moderately increased over the standard levelfor the patient's observed weight but showed aslight rise following resumption of normal activity(Figure 3).

As in the tettalogy, the values for plasma volumein other types of congenital anomalies show varia-tions which are near or slightly above predictedstandard values, except for the case of patent duc-tus arteriosus (Case 213) and of congenital mitralstenosis (Case 215). In the latter cases, the valueswere 79.8 ml. per kgm. and 109.0 ml. per kgm., re-spectively, which are 189 and 259 per cent ofstandard on an observed, and 140 and 229 per centof standard on an optimal, weight basis. Case 215,of congenital mitral stenosis, was in probable con-gestive failure preceding and at the time of thedeterminations.

In contrast to the findings in the tetralogy, how-ever, only 3 cases showed high total red cell vol-umes. Again, the patent ductus arteriosus andcongenital mitral stenosis show relatively highvalues (48.8 and 63.9 ml. per kgm.). The 3rd ex-ception, isolated pulmonic stenosis, was the onlycase in which the relationship of high red cell (72ml. per kgm.) and relatively standard plasma vol-ume (44.1 ml. per kgm.) simulated that found inthe tetralogy.

For the most part, the relative levels of plasmaprotein were within the standard range, as were thecalculated values for total circulating plasma pro-tein. Analysis of the data from the admittedlysmall number of cases fails to show any significantcorrelations between the total blood volume, redcell volume, total circulating hemoglobin or totalcirculating plasma protein and the hemoglobin per-centage and hematocrit.

DISCUSSION

The findings in this study lend support to thepoint of view that the increased cell volume seenin the tetralogy of Fallot is due to a compensatorystimulation of the bone marrow consequent to theanoxia resulting from inadequate aeration of thecirculating blood. Of the 3 prominent factorswhich might play a part in the development of the

anoxemia, it is evident from our data that theseptal defect is the least important. Thus, 2 of thecases of isolated septal defect (Nos. 221 and 223)showed significantly low hemoglobin and total cellvolumes, one case (No. 222) showed approxi-mately standard values, while the levels in the 4thcase (No. 220) were only mildly elevated. Thedextroposition of the aorta, on the other hand,must be considered as a possible factor, since itresults in mixing of unaerated blood from the rightside with aerated blood from the left ventricle.Blalock (19) has experimentally produced a simi-lar mixing by a pulmonary arteriovenous anasto-mosis following lobectomy in the dog which led toanoxemia and polycythemia.

The most important factor in the production ofthe anoxemia and the compensatory polycythemiaand hypervolemia, as seen in the tetralogy of Fal-lot, is probably the presence of pulmonic stenosis.This impedes the flow of venous blood into the pul-monic artery and forces the blood to pass into thesystemic circulation. Talbott and his colleagues(20) have estimated that 75 per cent of the bloodcirculating through the heart may not go throughthe lungs. In addition, the increase in viscosity isa striking feature in the tetralogy of Fallot. Wefound, as did Talbott and his colleagues, that theblood was so viscous that it was withdrawn onlywith difficulty. This must impose a real burdenupon the myocardium.

The combined action of these various factors re-sults in a chronic anoxemia which resembles thatseen in residence at high altitudes (21). The re-sulting polycythemia and hypervolemia are, ingeneral, conditioned by the degree, duration, andcontinuity of the anoxic stimulus. As long as thereis a marked discrepancy between the demands foroxygen by the tissues and the amount of oxygenfurnished to them by the circulating blood, thestimulus continues to operate and the level of cir-culating red blood cells remains high. In spite ofthe increased hemoglobin level, the oxygen satura-tion in many patients is at a critical level of about60 per cent. At this level, which corresponds toan oxygen saturation similar to that seen at analtitude of 4 miles, the margin of safety is small(19 and 20). The stimulus will be weakenedwhen either the demand for oxygen is decreasedor the supply increased. Prolonged bed rest thus

865


leads to a lessening of the stimulus and a decreasein the polycythemia. Likewise, the improvement inblood flow to the lungs and consequent increase inthe oxygen supply to the tissues brought about bythe Blalock procedure results in a decrease in thestimulus and in the polycythemia. The absence ofsignificant polycythemia and hypervolemia in theEisenmenger complex (Case 210) is to be ex-pected on this basis, since in this patient much lessvenous blood passes into the aorta directly or byway of the septal defect; a greater portion entersthe relatively wide orifice of the pulmonary arteryto be oxygenated by the lungs; less cyanosis is ob-served, and in general the cardiodynamics morenearly approach the normal. In the same manner,no marked polycythemia or hypervolemia is foundin patients with ventricular septal defects (Cases220, 221, 222, and 223), since there is no flow ofblood from the right to the left ventricle unlessleft ventricular failure is present. These patients,therefore, do not have arterial undersaturation andthere is no stimulus to bone marrow from anox-emia. It is difficult to reconcile the finding of anincreased red cell volume in isolated pulmonicstenosis (Case 209) with the fact that the arterialblood would not be expected to be undersaturatedin this condition. However, the similarity of theplasma and cell volume changes in our cases of iso-lated pulmonic stenosis and Fallot's tetralogy sug-gests a possible, similar etiological basis for thehypervolemia in these 2 diseases. Wecannot ex-plain the increase in plasma and cell volume in thecase of patent ductus arteriosus.

The fact that the chronic anoxemia of the tetral-ogy of Fallot does not modify the erythropoieticactivity permanently is of interest. Hurtado, Mer-ino, and Delgado (21) have shown that normal in-dividuals who have lived since birth at' high alti-tudes and are brought down to sea level, show aftersome time, blood characteristics similar to thosefound in normal individuals who have always livedat sea level. Similarly, decrease of the anoxemiain patients with tetralogy by bed rest or the Bla-lock procedure results in a gradual change towardsthe Wlood picture found in the so-called "normal"individual. The fate of the red blood cells involvedin this decrease awaits further study. The rela-tively gradual change and the absence of clinicalicterus suggests that the superfluous red cells al-ready in circulation are being destroyed while

fewer red cells are being elaborated by the bonemarrow.

The effectiveness of the polycythemia in thetetralogy seems to lie in the fact that it enables thepatient to meet his resting needs for oxygen al-though it may not provide for much margin ofsafety. The large volume of viscous blood, how-ever, imposes a rather severe strain on the heartwhich usually eventuates in congestive heart fail-

-ure in the patient surviving to the 3rd or 4th dec-ade, as cardiac reserve diminishes.

These studies are being continued. It wouldseem desirable to know much more about the un-derlying physiological adaptations of the circula-tion and respiration in congenital heart disease.Since among the most marked changes are thosewhich occur in red cell volume, it would be ofvalue to check further the validity of the dye-hematocrit method in these conditions by the car-bon monoxide or radioactive-iron techniques.The material gathered to date, however, indicatesthe possible usefulness of blood volume determina-tions in supplementing the usual tests for thedifferentiation of the various types of congenitalheart disease. The presence of an absolute eryth-rocytosis, as indicated by a significant increase inred cell volume without significant change in theplasma volume, should be interpreted as suggestiveof the presence of pulmonic stenosis. The serialdetermination of the blood volume and total cir-culating hemoglobin should also serve as a valu-able aid in indicating the optimal time for surgeryand as a measure of the beneficial effects of surgi-cal procedures.

CASE REPORTS

I. No. 208, W. M., 22 years

This patient gave a history of having been blue andhaving had dubbing of the fingers and curved nails sinceearly childhood. Relatives stated he had been blue sincebirth. He had severe dyspnea and many dizzy and faint-ing spells occurring on slight exertion. He had an acutethrombophlebitis followed by chronic leg edema and ul-ceration in 1943. This responded well to treatment con-

sisting of elimination of arterio-spasm by lumbar sym-pathetic blocks and compression dressings of elasticbandage or Unna's paste. In 1945 a high-low ligation forsuperficial varicosities was done on the right, afterwhich the low incision healed very slowly. He was alsoadmitted on one occasion with a diagnosis of "psychoticpersonality" and "gastric neurosis."

866


Physical examination on various admissions showed afairly well developed adult white male. The skin was ofa dusky blue color particularly marked in the ears andface. On exertion the cyanosis became more intense.No resting dyspnea was present, but exertional dyspneawas marked. Three-plus clubbing of the fingers andwatch-crystalling of the nails was present. Examina-tion of the chest revealed a loud precardial systolic mur-mur maximal over the pulmonic area. A systolic thrillover the same area was present. A 6-foot heart plateshowed a pulmonary conus concavity and a small aorticknob. Electrocardiogram showed pronounced right axisdeviation, and cardiography showed delay in right ven-tricle emptying. The aortic arch and descending aortawere demonstrated to be on the left when barium was in-troduced into the esophagus. Circulation time arm-to-tongue was 7 seconds with calcium gluconate. Determi-nation of circulation time with ether in this patient re-sulted in a measurement of arm-to-face circulation time of3.1 seconds as evidenced by severe burning of the face.The failure of this patient to smell the ether at any timeafter injection suggests that the amount of blood going tohis lungs was very small as compared to his total blood vol-ume. Arterial oxygen content was 18.35 per cent and ve-nous 11.29 per cent. Venous oxygen capacity was 27.28per cent. Venous pressure was 132 mms. of citrate;R.B.C.'s varied from 8 to 10 million. Other blood find-ings are given in Table I and Figure 2. Liver and kidneyfunction tests were normal.

Treatment with semi bed rest from January to March,1946, resulted in some improvement in exertional dyspneaand cyanosis, and resting cyanosis diminished. Attemptedanastomosis of the right subclavian-pulmonary artery onMay 9, 1946, by Dr. Alton Ochsner, was unsuccessful be-cause of the relative shortness of the subclavian artery.Following 6 weeks of intermittent right carotid compres-sion, anastomosis of the right common carotid-right pul-monary artery by the Blalock method was performed byDr. Ochsner. Following this, the patient's cyanosis di-minished for a few hours. He developed a left hemiplegia,however, and expired on the 3rd postoperative day.

II. No. 211, M. C., 6 years

The essential history on this boy, obtained from hismother, was that he had been blue since birth. The blue-ness was intensified by even slight exertion. He becameshort of breath upon slight exertion and as he becameolder had "falling out" spells~ on attempting exercise, suchas running or climbing stairs. His mental developmentwas normal and his physical development somewhat re-tarded. Positive physical findings were: (1) moderately.underweight; (2) increased duskiness of face, ears, lips,finger-nails, markedly -exaggerated on crying; (3) markeddubbing and watch-crystalling of fingers and toes; (4)loud precordial systolic murmur maximal over pulmonicarea; (5) right axis deviation and sinus tachycardia onE.C.G.; and (6) R.B.C. of 6 to 8 million.

This patient was observed and treated with bed rest fora period of 2 months, during which time there was no

change except questionably slight improvement of hisexertional dyspnea. He, at no time, had findings suggest-ive of congestive failure. On July 23, 1946, a Blalock-type anastomosis was done by Dr. Ochsner between theright subclavian and the right pulmonary artery. Im-mediate slight improvement in cyanosis resulted at thistime. Little blood having been lost during the operation,it was thought advisable, in order to decrease the bloodviscosity and because of danger of clotting, to withdraw150 ml. of blood. Withdrawal of this amount caused thepatient to go into severe secondary shock which wasquickly overcome by re-administration of the blood.

The patient's convalescence was uneventful. Only atrace of finger and toe clubbing and watch-crystalling re-mains. At present he has no resting-cyanosis and onlyslight exertional cyanosis. His exercise tolerance is muchimproved, his blood volume has dropped as previouslynoted (Figure 1). However, no murmur except the pre-viously presenA pulmonic murmur can be heard.

The prompt secondary shock sustained by this patientwhen, following Blalock's suggestion (19), 150 ml. ofblood was withdrawn postoperatively, raises the questionas to the desirability of bleeding in these cases. Thereseems to be no reason to anticipate a sudden shrinkage ofthe vascular capacity so as to produce increased viscosityand clotting. In fact, as Blalock has reported and we havefound, the changes towards "normal" occur graduallyover a period of weeks. It is more likely that the traumaof the relatively long operation produces a widespreaddilatation and temporary enlargement of the vascular bed,which certainly provides an adequate factor of safety dur-ing the early postoperative period.

SUMMARY

1. Plasma, red cell, and total blood volumes,total circulating hemoglobin, and plasma proteinwere studied in 7 cases of the tetralogy of Fallot,4 cases of isolated interventricular septal defect,and 1 case each of probable Eisenmenger complex,isolated pulmonary stenosis, coarctation of theaorta, congenital mitral stenosis, and patent ductusarteriosus.

2. All patients with tetralogy of Fallot and thecase of pulmonic stenosis showed a markedly in-creased blood volume due primarily to an increasein total red cell volume. Hematocrit and hemo-globin levels were also high. Plasma volume wasat, or slightly above, standard levels.

3. Bed rest and production of a new shunt bythe Blalock procedure in 2 cases resulted'in agradual decrease of red cell volume toward stand-ard values.

4. Blood volume was at approximately standardlevels in the cases of interventricular septal de-fect, Eisenmenger complex, and coarctation of the

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88W. NELSON, H. S. MAYERSON,J. H. CLARK, AND C. LYONS

aorta. The cases of congenital mitral stenosis andpatent ductus arteriosus showed high blood vol-umes due to increases in plasma volume as well asred cell volume.

Weare grateful to Miss Genie Burt and Dr. BlancheJackson for their assistance and to Drs. V. Platou andClarence T. Rae for their cooperation. The patients werehospitalized at Charity Hospital and Touro Infirmary.

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2. Fallot, A., Contribution A l'anatomie Pathologique deal Maladie Bleue (cyanose cardiaque). MarseilleMed., 1888, 25, 77, 138, 207, 270, 341, 403.

3. Abbott, Maude E. Atlas of Congenital Cardiac Disease.Am. Heart Assoc., New York, 1936, p. 60.

4. Glazebrook, A. J., Eisenmenger's complex. Brit.Heart J., 1943, 5, 147.

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7. Blumenfeldt, E., and Wollheim, E., Zur klinischenBeurteilung angeborener Herzfehler. Klin. Wchn-schr., 1927, 6, 396.

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9. Hallock, P., Polycythemia of morbus caeruleus (cy-anotic type of congenital heart disease). Proc.Soc. Exper. Biol. & Med., 1940, 44, 11.

10. Gregersen, M. I., Practical method for determinationof blood volume with dye-T-1824; survey of pres-ent basis of dye-method and its clinical applications.J. Lab. and Clin. Med., 1944, 29, 1266.

11a. Chapin, M. A., and Ross, J. F., Determination of truecell volume by dye dilution, by protein dilution,and with radioactive iron. Error of centrifuge he-matocrit. Am. J. Physiol., 1942,137, 447.

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16a. Davis, L. J.: Determination of blood volume in manwith Evans blue ("T-1824"). Edinburgh M. J.,1942, 49, 465.

b. Gibson, J. G., Jr., and Evans, W. A., Jr., Clinical stud-ies of blood volume; relation of plasma and totalblood volume to venous pressure, blood velocityrate, physical measurements, age, and sex in 90normal humans. J. Clin. Invest., 1937, 16, 317.

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