Cardiorespiratory responses to pregnancy and exercise in normal women and patients with heart disease

OBSTETRICS

Cardiorespiratory

responses to pregnancy

and exercise in normal women and patients with heart disease KENT

UELAND,

MILES

J.

JAMES

METCALFE,

Seattle,

M.D.

NOVY,

Washington,

M.D.* M.D. and

Portland,

Oregon

Serial measurements of blood oxygen transport were performed during pregnancy and post parturn in 6 normal women and in 16 women with mild heart disease. During pregnancy, normal women have an increased rate of oxygen consumption (Vo,) at rest regardless of posture. Early in pregnancy, the rise in cardiac output is proportionately greater than the increase in Vof, resulting in a decreased Cao,-flu,. Late in pregnancy, the V,,, continues to rise, but the resting cardiac output falls in the supine and sitting positions and the Cao,-C7o, widens. Standard sitting exercise costs more in terms of Vol during pregnancy, and the heart assumes a greater share of the burden for supplying the oxygen needs to the periphery in normal patients. In women with mild heart disease, the resting cardiac output and Vol during pregnancy is lower and they show a smaller increment in response to standard sitting exercise. The average Cao,-Ciio, at rest throughout pregnancy and post partum is wider. Patients with mitral stenosis, in particular, have a low cardiac output and a consistently wider Cao,-Ciro,. During exercise, the handicap in cardiac output and peripheral oxygen supply becomes even more apparent in this group of women. There is no accumulation in oxygen debt during exercise at any time in the study, and blood lactate and pyruvate concentrations during and after recovery from exercise show no significant differetrces attributable to either pregnancy or to heart disease.

Heart Association, and Ford Grant No. 63-568 (Training in Riology of Reproduction).

From the Department of Obstetrics and Gynecology, University of Washington School of Medicine, and the Heart Research Laboratory, Department of Medicine, University of Oregon Medical School.

Received Accepted 1972.

This investigation was supported in part by United States Public Health Service Cardiovascular Program Project Grant No. HL 06336, Research Grants Nos. HL 06042 and HL 14121, Grant No. HL 05499 from Heart and Lung Institute,

for publication for

publication

July

Foundation Program 20, 1972.

August

14,

Reprint requests: Dr. K. Ueland, Dept. of Ob./Gyn., University of Washington, Seattle, Washington 98295. *Present addr-ess: Dept. of Ob./Gyn., University of Oregon Medical School, Portland, Oregon 97201.

and Training the National the Oregon

4

\‘duur

113

Cardiorespiratory

0 u R K N o 1%’L E D G E of the cardiorespiratory responses of women to pregnancy is characterized by conflicting and incomplete information,‘, ‘I( a, “, I’ and this is especially true of avomen Lvith heart disease. We have previously reported the hemodynamic repregnant women to s]~on”c’ of normal changes in body position and to exercise.’ Patients with various kinds of heart disease, although they cvere only mildly symptomatic or even completely asymptomatic, sho\ved striking differences from normal.!’ The present report deals with blood osygen transport and its modification during pregnancy in normal women and in women with mild heart disease. Studies were made at rest in scavrral positions and during bicycle exercise of standard intensity. Material

and

methods

Serial studies were carried out in 6 normal lvomen and 16 ivomen with heart disease during pregnancy and post partum. Each patient was studied 6 to 8 weeks post partum and during one or more of the following periods of pregnancy: 20 to 24 weeks, 28 to 32 weeks, and 38 to 40 weeks. Studies were done in the morning while the patients were fasting. The procedures were carefully explained to each patient. A polyethylene catheter was inserted into an antecubital vein through a 16 or 18 gauge needle. A brachial artery \vas also catheterized percutaneously with a Cournand needle. a nylon leader, and a polyethylene catheter. The measurements were not started until the patient’s pulse rate and respiratory minute volume were stable following these preparative procedures. Oxygen consumption was measured with a Tissot spirometrr and Scholander analyses of expired air. Blood gases were determined with a manometric technique.“’ Cardiac output was measured by the dye-dilution method with the use of indocyanine green dye and a continuously recording densitometer. Samples of arterial blood for lactate and pyruvate analyses \vere drawn lvith the patient sitting at rest. during exercise, and sitting after 10 minutes of rrcovery. These were performed

responses

to pregnancy

and

exewse

5

by Dr. William A. NeilI’s* laboratory by chemical methods.” The arteriovenous OSJ’gcn concentration difference and nliscd \‘enous oxygen content were calclllatetl from the measured oxygen consumption, tile cardiac output. and the arterial blood oxygen content. In each study, measurrrncn!r Tvcrr lllade lvith the patient supine, sitting :lt rest. esercisc at 100 Mopon mrters durin,q (k.p.m.! on a bicycle ergometer. and sitting at rest after exercise. At least 5 minutk>s were nllolved for stabilization with each ;.h:mqe in position. Measurements made cllLrine taxercise were begun after 3 minutes of rxer&ca. Results Our data are presented according to the following patient groupings: i 1 ‘: ncrrnai women (6 subjects i ; (2 i Lvomen v,+tll heart disease (16 patients) : (A ) predominant rnitral stenosis (6 patients-2 in functional Class I of the New York Heart Assoc,iatioll. .1 in Class 11). (B) patients in functional Class I (7 patients--2 \vith predominant aortic regurgitation, 2 with predominant aortic stenosis. and 3 with congenital pr!lrnonic stenosis j , and (Cl patients in functional Cl-‘ISS II (3 patients--one with predominant aortic regurgitation and 2 with Starr-Edwards aortic valve prostheses to correct predominant aortic stenosis). Fiq. 1 presents our data on os~~w~ consumption (Vo,) at rest in the supine positiol!. In normal patients, therp is ;i small but progressive increase in oxygen consumption as pregnancy advances. The el*~vation (compared to postpartum values) I rarhes significance (p < 0.025) at 28 to 32 lvceks’ gestation. In patients with heart rtland Veterans Administration Hospital. Portland. Orwor~

6

Ueland,

Novy,

and

Mekalfe

ues early in pregnancy and post partum. Fig. 3 presents our data on oxygen consumption in the sitting position. Resting Qo, is increased during early pregnancy and continues to rise as pregnancy progresses, reaching 331 ml. per minute late in pregnancy, approximately 50 ml. per minute above the nonpregnant level for normal subjects sitting at rest. There is also a progressive rise in 26-32

20-24 Weeks

Fig. 1. Oxygen meters

per minute)

38-40

6-6 weslw

Gsrtotion

consumption (Go,) at rest, supine.

POstpartYm

(cubic

centi-

Qo, during standard exercise in normal subjects as pregnancy advances, but the change is not statistically significant. When all patients with heart disease are considered together, their vo, sitting at rest during early pregnancy is similar to that of normal patients. As pregnancy advances, the VO, of the cardiac patients (at rest in the sitting position) does not rise as does that of the normal subjects, but the differences are

20:24

z&32

t

Week*

Fig. 2. Calculated (Ca0JX~)

(vol.

36-40

Gertotio”

618 Weeks

Portportum

arteriovenous oxygen differences per cent) at rest, supine.

ferences in oxygen consumption during pregnancy. Fig. 2 shows the calculated arteriovenous oxygen differences (Caoz-Go,) of all the patients in supine recumbency. In the normal women, the Cao&voy is decreased during early pregnancy, consistent with the increase in cardiac output which is proportionately greater than the increase in oxygen consumption. However, at 28 to 32 weeks it approximates nonpregnant values and at 38 to,40 weeks it significantly exceeds the values recorded post partum (p < 0.01) . The patients with Class I heart disease have values similar

to

those

of

normal

women

during

most of pregnancy, but near term they have a narrower Caon-Goo,. The patients with mitral stenosis maintain high Caoz-Goo, val-

not statistically significant. The Vo? response to standard exercise is significantly different from that of normal subjects (p < 0.01) at 20 to 24 weeks and at 28 to 32 weeks of gestation. The patients with Class II heart disease continue to have a significantly lower (p < 0.01) ‘cio, during standard exercise in the postpartum period. The differences in %‘o, between normal subjects and women with heart disease cannot be attributed entirely to differences in body size: average body surface area (B.S.A.), calculated post partum, was 1.68 M.* for the normal patients and 1.61 M.? for those with Class II heart disease. Fig. 4 presents the average calculated arteriovenous oxygen differences at rest and during standard exercise in all groups. In the post partum studies, the Caon-C70z is wider in all our patients with heart disease. During early pregnancy (20 to 24 weeks) and midpregnancy (28 to 32 weeks), the Cao&JoS declines in all patients except those with mitral stenosis studied at 20 to 24 weeks of pregnancy. As term approaches, the Cao,CVo? returns toward nonpregnant levels. During all study periods in pregnancy and post partum, the patients with mitral stenosis consistently have the widest Cao&70z sitting at rest, and during exercise this becomes even

\‘olurnt. NunLlxT

115 1

Cardiorespiratory

responses

to

Fig. 3. Oxygen consumption (90~) (cubic centimeters per minute) standard sittmg exercise (100 k.p.m.) for 3 minutes.

pregnancy

and

exemse

7

sittinq at rest and durinc

6-

Fig. 4. Calculated arteriovenous oxygen differences (Cao,-Go,) and during standard sitting exercise (100 k.p.m.) for 3 minutes. more pronounced. Patients with Class I heart disease show responses similar to the normal patients during early pregnancy (20 to 24 weeks) and mid-pregnancy (28 to 32 weeks) both sitting at rest and during exercise. Late in pregnancy, however, the patients with Class I heart disease show a greater rise in Cao&Vol with exercise than do normal patients. Table I summarizes the data for all our patients, including mean cardiac output. It is of interest to note that in nearly every instance, both during pregnancy and post partum, the cardiac output, oxygen consumption, and Caon-Ccoz return to pre-exercise levels by 10 minutes after exercise. Table II shows the comparative data for

(vol. per cent) sitting at rest

B.S.A. for each category of patients studied. The postpartum values are used. In general, the differences are not great, but our patients with mitral stenosis had a B.S.A. which was 7 per cent smaller than the control group. Blood concentrations of lactate robe to a mean level of 1.283 during exercise while pyruvate levels rose to a mean of 0.195. After 10 minutes of recovery, the conctantrations were 1.400 for lactate and 0.220 for pyruvntp. There was no significant difference in these concentrations (or in the blood lactatc/pyruvate ratio) during pregnancy and post partum or between normal subjects and women with heart disease, so values for all our patient groupings were used in c:.Jculating these mean values.

8

Ueland,

Novy, and Metcalfe

Table I. Cardiac

output,

oxygen

consumption,

and arteriotcnous

Supine Weeks’ gestation

Patient cate,oory

20-24

Heart

Heart

Heart

M.S.

=

=

Qb

Heart

Mitral

“One

stenosis.

output

iice = Oxygen Cao,-CGo, =

H.D. (litrrs

consumption Arteriovenous

‘38 2.37 254 244 255

3.6 5.0 7.7 5.0 3.8

6.14 4.X xi5 4.66 5.94

‘96 273 320 299 292

4.8 6.4 9.3 6.4 4.9

8.96 6.33 4.76 6.73 10.44

3.38 4.10 5.12 5.16 6.41

24ll 230 356 546 267

4.5 5.6 5.0 4.8 4.2

5.43 4.87 4.68 5.04 5.92

269 264 274 271 297

5.0 5.4 5.9 5.4 5.0

4.48 -3.79 4.34 4.88

244 167 228 303

5.5 4.4 5.3 6.2

4.7.3 282 3.70 249 4.52 275 5.57 330

6.0 _ 6,7 6.1 5.9

441 3157 4.21 4.18 5.12

212 218 223 217 219

48 6:l 5.3 52 4:3

3.76 3 23 3.39 3.52 4.83

6 ..i 7.2 7.6 7.0 5.8

= pa

Heal

cjb

I;‘o,

Cao,00.

Cao.1 Go,

(ib

+02

601 6.7 442 7.0 598 12.6 560 8.3 744 7.1

5.61 4.10 3.40 4.43 5.96

200 278 302 289 293

5.0 6.0 a.9 6.5 4.9

7.97 6.90 6.53 7.93 ..+ 9.96

618 5’9 587 597 762

7.8 7.7 9.0 a.3 7.7

4.63 4.90 3.7.1 4.34 6.58

276 241 283 276 273

5.9 4.9 7.6 6.4 4.2

7.23

710

9.8

.5.41 644 6.87 697 10.12 a36

11.9 10.2 a.3

4.53 3.89 4.37 6.32

298 224 339 331

6.6 5.0 6.3 5.6

t diseasr.

Class

I and

Class

“46 23 1 2.59 ‘47 281

10.3 10.1 10.8 10.5 a.8

3.65 x8.5 3.23 3.35 4.94

259 235 243 249 271

7.1 a.3 7.5 7.4 5.5

II -NW

6.08 :i.ll 5.83 :?.a1 a.24 York

Heart

625 514 631 607 728

Association

Functional

Clasrification.

per minute). (calculated).

patient.

area body

Patient

category

Heart

disease

Postpartum surface (M.‘)

Class I Class II M.S. All H.D. Normal abbreviations,

area

1.61 1.61 1.56 1.60 1.68 see footnote

to l‘able

I.

Comment During pregnancy,

women have an increased rate of oxygen consumption (qo,) at rest, regardless of posture (Figs. 1 and 3). Early in pregnancy, the increase in cardiac output (probably on a hormonal basis) is proportionately greater than the increase in

%;:

-

minute).

(cubic centimeters osyg~n diiTel ence

Table II. Body surface

For

ijo?

Sitting exrrcise)

disease

Class I Class II M.S. All H.D. Normal

Cardiac

46

(after

disease

Class I Class II M.S.” All H.D. Normal 6-8 Weeks post partum

6.54 4.70 3.29 4.86 6.80

?;;:

Sitting (exercise)

Sitting exercise)

disease

Class I Class II* M.S. All H.D. Normal 38-40

tie,

difference

disease

Class I C!ass II M.S. All H.D. Normal “a-32

D,b

(before

oxygen

$‘o,.

Thus,

the

Cao,-Go?

is decreased

(Figs. 2 and 4)) suggesting that average tissue oxygen tension (PO*) is increased. Late in pregnancy, the resting cardiac output falls when the normal woman lies in the supine position; in order to supply the increased co, at term, more oxygen is extracted from each unit of blood flow, that is, the Cao,In the sitting position, the FA\ o.! widens. at term is similar to that enCa,,,-CT,j, countered in the nonpregnant sitting individual. Table III lists our data on 90, and Cao-Go, for normal women, together with values according to reported by others, arranged position, weeks of pregnancy, and response to exercise. Our data suggest that standard exercise on a bicycle ergometer costs more, in terms of oxygen consumption, at term than it does earlier in pregnancy or post

V~hnr

1l.i

Number

1

Cardiorespiratory

Table III.

Data

according

to position,

weeks’

responses

gestation,

to

and response Weeks’

Postpartum Author

20-24

28-32

1.61

243

-

255

-

267

Supine

1.59

209*

3.8

216

4.6

1.63

226

-

234

Supine

1.58t

218

3.4

Supine

1.68

25.3

Recumbent (bicycle pedaling, steady rate) Sitting (bicycle ergometer-150 k.p.m.) Sitting (bicycle ergometer-l 00 k.p.m.)

1.58

(probably)

9

6 Weeks postpartum

35-40

Recumbent

Supine

exercise

gestation

VO?

Positbn

and

to exercise

B.S.A. fM.*)

and year

Rest Widlund, 194:i” Palmer and Walker, 19496 Cugell and associates, 1953” Bader and colleagues, 1955l Ueland and coworkers, 19729

pregnancy

eio:

Cm,cc1

-

21(,

.-

1.51

4.4

TO7

4.5

-

238

-

196

230

3.5

242

4.4

--

--

3.9

267

4.5

303

6.3

219

4.3

363

4.5

403

5.0

403

5.8

--

-

(Weight 57.2 Kg.)

530

9.0

570

8.8

570

9.1

5 30

11

1.68 (Weight 63.6 Kg.)

744

7.0$

762

7.9

836

8.2

7”8_

Ca0,ci%:

tioi

Ca0,cso,

For

Cao,cEII

Exercise Bader and leagues,

col1955l

Guzman and Caplan, 19704 Ueland and coworkers, 1972” U.S.A.

= Body

surface

area

in square

9.1

-.-

meters.

= Oxygen consumption (cubic centimeters per minute) Cao-CFn, = Arteriovcnous difference (volume per cent). from cardiac output, Cao, - GO,. *v02 calculated tB3.A. at 14 to 24 weeks gestation, no postpartum studies.

VOZ

:Cao-Go,

calculated

from

cardiac

output

and

oxygen

partum although the difference is not statistically significant, either in our study or that reported by Guzman and Caplan.’ The explanation for an increased vo, during standard sitting exercise in pregnancy may lie in a greater response of the heart and increased mechanical work of breathing to a standard work load. This tentative explanation is strengthened by the data in Table I. In all study periods during pregnancy, exercise evokes a greater cardiac output than does the same standard exercise post partum. During pregnancy, the CaozCV,,, does not rise as high during standard exercise as when the patient is not pregnant. At 20 to 24 weeks’ gestation, this difference is statistically significant (p < 0.01). From the viewpoint of cardiac work, oxygen is supplied to the periphery less efficiently during pregnancy. From the standpoint of tissue osygenation, on the other hand, the

conrumption.

greater cardiac output provides a high mean oxygen tension in the peripheral capillaries, especially in early pregnancy, during rxercise as well as at rest. The peripheral tissues (or some of them) are hyperemic during early pregnancy, not only at rest in the sitting position but also during sitting exercise. Expressed another way, some tissues have their oxygen needs supplied at a relatively high PO, early in pregnancy, and this adjustment persists during exercise in the sitting position. The specific tissues so privileged have not been identified, but most likely the kidneys and uterus are favored.? It seems clear that during pregnancy the heart takes more than its usual share of the burden of supplying the oxygen needs of the periphery in normal patients. The increase in Vo, shown by our data in response to a standard work load in pregnancy does not confirm the observations of

10

Ueland,

Novy,

and

Metcalfe

Seitchik.’ His data, on 195 women (each an insignificant destudied once), showed crease during pregnancy in the total energy cost of standard exercise on a bicycle ergometer, and the anaerobic cost of the work was unchanged during pregnancy. We have no explanation for this basic disagreement, but it may reflect the greater variability in studies which arc not performed serially in the same group,of patients. The patients with heart disease are clearly different from those women with normal hearts in respect to mechanisms of oxygen transport. In general, their cardiac output is lower even at rest than that of normal tvomen, and throughout pregnancy and post partq their average Ca,,,-Go, is wider. Mitral stenosis seems to be a particularly bad lesion in this respect; the cardiac output of women with this lesion is lower throughout pregnancy, and the Cao&7~, is During exercise, the consistently wider. handicap on cardiac output and peripheral oxygen supply is even more apparent: in women with mitral stenosis the tissue demands for oxygen are met by an increasing extraction of oxygen from the circulating blood. which may lead to critically low osy~qen tensions in some tissues. The lolver resting Go, found in our patients with heart disease (in comparison with normal women) remains unexplained. It is undoubtedly due in part to their slightly

smaller body size (see Table II). At term the lower resting ?o, of cardiac patients ma);dso be clue in part to the smaller average birrh weight of infants born to mothers with heart disease.” During standard exercise, the vo, rises less in women with heart disease than in normal women, and this difference was persistent throughout pregnancy and post partum. It is tempting to suggest that the women with heart disease were accumulating an oxygen debt during exercise, but our data lend no support to this idea. Oxygen consumption, cardiac output, and Cao,-CVo2 all return to pre-exercise values within 10 minutes after exercise, suggesting that there is no buildup in oxygen debt. This result agrees with those obtained by Widlund” in studying mild or medium to hard exercise in normal women throughout pregnancy. Widlurid*’ did find a relative oxygen debt (15 per cent or h.igher) in pregnant women after harder work, but even then the values were not statistically different from control nonpregnant women. Our values of blood lactate and pyruvate concentrations during esercise and after 10 minutes of recovery showed no significant differences attributable to pregnancy or to heart disease. Further study is justified to determine the energy costs of exercise during pregnancy and how these costs arc paid, especially by women with heart disease.

REFERENCES

1. Bader, R. A., Bader, M. E., Rose, D. J., and Braunwald, E.: J. Clin. Invest. 34: 1524, 1955. 3. Burwell, C. S., and Metcalfe, J.: Heart Disease and Pregnancy: Physiology and Management, Boston, 1958, Little, Brown & Company, p. 17. 3. Cugell, D. W., Frank, N. R., Gaensler, E. A., and Badger, T. L.: Am. Rev. Tuberc. 67: 568, 19.53. 4. Guzman, C. A., and Caplan. R.: AM. J. ORSTE.F. GYNECOI.. 108: 600, 1970. 5. Huckabee, W. E.: J, Appl. Physiol. 9: 163, 1956.

6. 7. 8.

9. 10. 11.

Palmer, A. J., and Walker, A. H. C.: Obstet. Gynaecol. Br. Emp. 56: 537, 1949. Seitchik, J.: AM. J. OBSTET. GYNECOL. 97: 701, 1967. Ueland, K.. Novy, M. J., Peterson, E. N., and Metcalfe, J.: AM. J. OBSTET. GYNECOL. 104: 856, 1969. Ueland, K., Navy, M. J., and Metcalfe, J.: Anl. J. OHSTET. GYNECOL. 113: 47, 1972. Van Slyke, D. D., and Neill, J. M.: J. Biol. Chem. 61: 523, 1924. Widlund, G.: Acta Obstet. Gyneco!. Stand. 25: 1, 1945. (Suppl.)