Chapter 8
Cardiorespiratory Physiology of Pregnancy
Barbara B. Head, James E. Ferguson III and James E. Ferguson II
Main Menu   Table Of Contents

Search

Barbara B. Head, MD
Assistant Professor, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, Virginia; The Perinatal Center at Johnston-Willis Medical Center, Richmond, Virginia (Vol 3, Chap 8)

James E. Ferguson III, MD
Medical Scientist Training Program (MSTP), Integrative Vascular Biology Program, School of Medicine, University of North Carolina, Chapel Hill, North Carolina (Vol 3, Chap 8)

James E. Ferguson II, MD
John N. Nokes Professor and Director, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Virginia School of Medicine, Charlottesville, Virginia (Vol 3, Chap 8)

 
PREGNANCY-INDUCED CHANGES
MATERNAL EXERCISE
LABOR-INDUCED AND DELIVERY-INDUCED CHANGES
ACKNOWLEDGMENT
REFERENCES

The first measurement of cardiac output in a normal pregnant woman was performed by Lindhard1 in 1915. Using a nitrous oxide technique, he found an increase in cardiac output of approximately 50% during pregnancy. In 1926, Gammeltoft2 first observed that late in pregnancy the cardiac output tended to decline toward nonpregnant levels. He attributed this change to a decline in maternal physical activity. The careful observations and measurements reported by Burwell and associates3,4 in 1938 helped greatly to delineate many of the pregnancy-related hemodynamic changes. They noted changes in heart rate, blood pressure, venous pressure, and cardiac output in serial basal measurements in a small group of women studied throughout pregnancy. These changes persist throughout pregnancy and generally regress after delivery5,6; however, there may not be a return to prepregnancy levels.7 Invasive and noninvasive techniques have elucidated further the alterations in cardiovascular physiology during normal pregnancy.

Back to Top
PREGNANCY-INDUCED CHANGES

Cardiac Output

Cardiac output increases significantly during pregnancy. The increment of 50% initially reported by Lindhard1 in 1915 is similar to the values reported in the 1980s and 1990s using more refined methodology, such as cardiac catheterization and dye dilution measurements.8,9,10 Results of several serial studies suggest that cardiac output rises significantly the first trimester of pregnancy,10,11,12 continues to rise through 26 to 34 weeks’ gestation,9,13,14 and is maintained at an elevated level to term if measured while the patient is in lateral recumbency.9,11 The net result of these hemodynamic alterations is that early in pregnancy the increase in cardiac output at rest is accomplished predominantly through an increase in stroke volume. As pregnancy advances, however, heart rate increases, and stroke volume decreases to nonpregnant levels; the increase in heart rate is responsible for maintaining the elevated cardiac output. A review of the changes in cardiac output during pregnancy suggests that cardiac output varies widely among individuals with singleton pregnancies in the third trimester,15 and the increase in cardiac output is even greater in a twin pregnancy.16,17 Ueland and coworkers9 found a decline in cardiac output, however, between 38 and 40 weeks’ gestation for all positions studied (i.e., supine, sitting, and lateral recumbency), but the only statistically significant decline was encountered in the patients studied while supine. Doppler and echocardiographic studies have confirmed these changes in cardiac output.6

Heart Rate

The rise in heart rate during pregnancy reaches 10 to 15 beats/min above nonpregnant values for most maternal positions.9 With the exception of the sitting position, the increase seems to be progressive until term.

Stroke Volume

Stroke volume is elevated to peak levels early in pregnancy (20 to 24 weeks’ gestation) and progressively declines to nonpregnant levels at term.9 For the supine position, the stroke volume at term is 20 mL less than that measured 6 to 8 weeks postpartum.

Respiratory Physiology

Respiration includes the transfer of oxygen from the external air to the blood in the maternal pulmonary capillaries and oxygen consumption by the peripheral tissues. The maternal rate (including fetal) of oxygen consumption rises progressively during pregnancy, reaching a peak of 20% above nonpregnant levels.18 The oxygen consumption of women at rest (but not basal) increases even more during pregnancy than does the basal value.19,20 The total rate of maternal oxygen consumption in the pregnant woman is the sum of the rates of each of her tissues and that of the fetus and placenta. Approximately two thirds of the total increment in basal oxygen consumption during pregnancy is accounted for by the combined consumption of the fetus, placenta, and uterine muscle. The remaining increment is due to the increased oxygen requirements of the maternal myocardium, kidneys, muscles of ventilation, and mammary glands. As might be predicted, the oxygen consumption is greater when measured in women with multiple gestations compared with singleton gestations.21 The onset of labor is associated with a doubling in the average oxygen consumption and a threefold increase when measured during a uterine contraction.22 The discrepancy between increases in cardiac output and oxygen consumption and the concomitant early fall in peripheral vascular resistance were compared by Burwell23 with the hemodynamic changes of an arteriovenous fistula. From a teleologic standpoint, these alterations seem to anticipate reproductive needs because there is a rich flow of well-oxygenated blood to the uterus during early pregnancy when organogenesis is occurring and before fetoplacental circulation is fully developed. The arteriovenous oxygen difference widens to nonpregnant levels later in pregnancy. The well-known pregnancy-associated changes in maternal ventilation are discussed elsewhere in this volume.

Ventricular Function

The steroid hormones of pregnancy, particularly estrogen, not only affect vascular resistance, but also seem to have a direct effect on myocardial muscle. The mode of action is uncertain, but estrogens are structurally similar to the cardiac glycosides. It has been postulated by Csapo24 that estrogens may alter the actomyosin adenosine triphosphatase (ATPase) relationship in the myocardium, increasing myocardial contractility. More recently, measurements of systolic time intervals have been performed in humans during the first and second trimesters.25 The pre-ejection period of left ventricular systole is reduced, particularly in the second trimester. The cause of this change in ventricular dynamics is unclear, but it could be due to a direct action of steroid hormones on myocardial cells.26 Male transsexuals given high-dose estrogen therapy show increases in myocardial contractility.27

Dramatic changes in cardiovascular function have been shown by echocardiographic studies during the course of normal pregnancy. Gilson and colleagues28 studied indices of ventricular remodeling in primigravid women during gestation compared with the postpartum state. Left ventricular diastolic dimension did not change, whereas there was a significant increase in left ventricular end-diastolic volume. The ventricular diameter-to-length ratio did not change, but the left ventricular posterior wall thickness increased with advancing gestation. The radius-to-wall thickness ratio decreased in mid-to-late gestation. No significant change occurred in left ventricular mass.28 When evaluating indices of ventricular contractility, these investigators did not find any significant changes in ejection fraction, fractional shortening, or velocity of circumferential fiber shortening. The rate-corrected ejection time and left ventricular wall stress were each less, as was the ratio of wall stress to velocity of circumferential fiber shortening (a load-independent assessment of left ventricular function). They concluded that independent of the increased preload and heart rate (reflected in velocity of circumferential fiber shortening) and of the decreased systolic blood pressure (reflected in wall stress), the intrinsic myocardial contractility was enhanced.28 Other investigators studying a smaller number of patients found no change in ventricular contractility.29

Vascular Resistance

Maternal vascular resistance (systemic and pulmonary) decreases progressively throughout gestation.6 This decline mirrors that of the decline in systolic and diastolic blood pressures.30 Hypotheses for the cause of this vasodilation include decreased pressor responses to angiotensin II in pregnant women, increased vasodilatory prostaglandin synthesis, and alterations of extracellular matrix proteins in the vasculature. Nitric oxide (NO) has been studied intensively and is a frontrunner for this role.31,32 NO is a short-lived molecule that is synthesized by NO synthase in the endothelium after stimulation and is released into the interstitium to exert its effect locally. In vascular smooth muscle, NO stimulates cyclic guanosine monophosphate (cGMP), which reduces cellular calcium concentrations and inhibits contraction. NO and cGMP have been found in increased concentrations in pregnant animals and can be reduced by the estrogen receptor antagonist tamoxifen, implying that estrogen modulates these increased levels of NO. Weiner and Thompson32 hypothesized that the varying effects of pregnancy on vascular resistance in different organs could be due to differential levels of estrogen receptors on the endothelium.

The role of steroid hormones on NO levels has been elaborated by studies that have suggested a role of fetal dehydroepiandrosterone sulfate (DHEA-S) in maternal vasodilation.33,34 DHEA-S is produced by the fetal adrenal gland and is metabolized by the placenta to estrogen, which then enters the maternal circulation. In these studies, pregnant women at term were infused with DHEA-S with monitoring of estrogen and nitrite levels. Nitrite levels doubled after DHEA-S infusion and peaked at 10 minutes after infusion. Estrogen levels increased fivefold and peaked at 60 minutes after infusion. The temporal relationship of the peak levels of nitrites and estrogen suggests that there may be other pathways involved in this process and that the fetus may play a role in regulating maternal blood pressure and volume through DHEA-S production. The statistical power of these studies is limited, however, by the small number of patients studied.

Blood Volume

Blood volume, composed of plasma volume and red blood cell (RBC) mass, increases 20% to 100% during pregnancy.35,36 The rise begins in the first trimester and continues throughout pregnancy but at a much slower rate during the third trimester.35,37,38 The total increment seems to depend on several factors, including maternal weight36 and the weight of the products of conception.36,39,40 Expansion of the plasma volume (40% to 50%) is responsible for most of the increase in blood volume, especially between the 6th and the 24th weeks of pregnancy. Further minimal expansion occurs in the third trimester. RBC mass increases progressively throughout pregnancy. The increment in total RBC volume ranges from 20% to 35% when compared with nonpregnant values.35 The “physiologic anemia of pregnancy” results from the disproportionate expansion of plasma volume compared with RBC mass. The resulting hemodilutional anemia is maximal between 16 and 22 weeks of pregnancy, but hematocrit and hemoglobin values increase in the third trimester because the RBC mass continues to expand, whereas plasma volume increases only minimally.41 Multiple gestation is associated with a greater expansion of the blood volume; however, the presence of a fetus is not required.35,42 Even when iron stores are adequate and iron supplementation is provided, there is a decline in hemoglobin and hematocrit values late in pregnancy, but in some instances the fall is not statistically significant.18,43,44,45

The previously reported decline in plasma and blood volume late in pregnancy was probably in error. In 1971, Chesley and Duffus46 showed the effect of posture on plasma volume late in pregnancy and consistently found a lower plasma volume in patients studied in the supine position than in patients in lateral recumbency. They attributed the findings to inferior vena caval occlusion, resulting in improper mixing of the dye (Evans blue) and extravasation of fluid into the lower extremities because of the elevated venous pressure.

Failure of the maternal blood volume to expand normally may be associated with suboptimal maternal and fetal outcomes, including impaired fetal growth,47,48 and may occur at 5 weeks’ gestation.49 Longo50 hypothesized that the fetus may regulate the increment in maternal blood volume through the production of DHEA-S by the fetal adrenal gland. As described earlier, DHEA-S is the precursor of placental estrogens, which may play a role in vasodilation through NO production, triggering a compensatory expansion of blood volume through the renin-angiotensin-aldosterone axis. It has been shown that DHEA-S itself may play a role in this vasodilation.34

Structural Alteration of Blood Vessels

The sudden appearance of spider angiomas during pregnancy is common, as is the occurrence of palmar erythema. Both of these events are thought to be hormonally mediated. Burwell and Metcalfe51 reported the rapid growth of a pre-existing arteriovenous fistula during pregnancy. Rupture of splanchnic artery aneurysms is more common in women than in men before the age of 45. Most of these aneurysms rupture between the seventh and ninth months of pregnancy.52 Rupture of cerebral aneurysms also have been reported to occur more frequently during pregnancy. The chance that a subarachnoid hemorrhage will occur increases with each trimester of pregnancy.53

Histologic changes have been reported to occur in the wall of the aorta during pregnancy,54 but whether or not these are related to vessel strength and contribute to aortic dissection or rupture is open to question.55 The exact mechanisms responsible for the many hemodynamic alterations associated with pregnancy are unclear, but undoubtedly many factors are involved. Neither the role played by the fetus nor that of the hypervolemia of pregnancy is known. From the data presented in the literature, the sex steroid hormones must play an important part. Observations by Ueland and Parer56 that the intravenous infusion of natural estrogens in nonpregnant ewes produces an increase in cardiac output similar to that encountered in pregnancy in the same animals support this theory. Similarly the findings by Walters and Lim57 of an increase in cardiac output (15%) and in plasma volume (300 mL) in women taking oral contraceptives provide further evidence of the important role of the sex steroids.

Maternal Posture

In 1953, Howard and colleagues58 first published their data on the supine hypotensive syndrome of late pregnancy. They showed, by manometric measurements, that the fernoral venous pressure was highest when patients were in the supine position and attributed this to inferior vena caval occlusion by the gravid uterus. These findings later were confirmed by Scott and Kerr,59 who studied pressure changes in the inferior vena cava in patients undergoing cesarean section. In 1964, Kerr and associates60 convincingly showed, by angiographic techniques, total occlusion of the inferior vena cava late in pregnancy in a patient in the supine position. Two subsequent serial hemodynamic studies during pregnancy, using dye dilution techniques to estimate cardiac output, showed the effect of maternal posture.9,11 Early in pregnancy (8 weeks) and up to 24 weeks’ gestation, cardiac output remained essentially unchanged when measured in the supine and lateral positions. In both studies, there was a statistically significant decrease in cardiac output (25% to 30%) when measured in the supine position at 38 to 40 weeks’ gestation. The decline was entirely attributable to a drop in stroke volume because heart rate remained relatively constant. Maternal upright positioning causes symptoms of syncope, however, in 8% of pregnant women in the first trimester of pregnancy. In the second trimester, the gravid uterus impairs venous return in standing women and can cause cardiovascular disturbances.61

Using aortography, Bieniarz and coworkers62 showed that the arterial side of the vascular tree also was affected to some degree by the large gravid uterus at term. They showed lateral displacement, attenuation, and elongation of the distal aorta as it was compressed against the maternal spine in supine recumbency. During hypotension, this effect becomes more pronounced.

Back to Top
MATERNAL EXERCISE

There is conflicting information in the literature regarding the maternal cardiorespiratory response to exercise. This controversy can be attributed in part to the different ways in which the patients were exercised, the maternal posture, and the techniques used to measure the hemodynamic response.

Standard treadmill exercise (weight bearing) is associated with higher rates of oxygen consumption in pregnant women than in women in the postpartum period.63 A consistent increase in oxygen consumption has not been noted when non–weight-bearing exercise has been studied in pregnant women. In a serial study by Ueland and associates,9 the increment in cardiac output during mild, standardized, non–weight-bearing exercise on a bicycle ergometer was found to be the same throughout pregnancy and postpartum. Serial measurements of blood oxygen transport during exercise in this same group of patients64 showed that exercise of mild intensity was associated with an increased oxygen requirement and cost more in terms of oxygen consumption during pregnancy. In contrast, Knuttgen and Emerson63 reported a slight decrease in oxygen consumption when a similar group of patients were studied in the pregnant and the nonpregnant state. Metcalfe and colleagues65 evaluated the effect of regular exercise before and during pregnancy and noted that neither the oxygen cost of steady-state exercise nor the oxygen debt incurred by exercise was elevated during pregnancy.

With moderate exercise, the rise in cardiac output seems to be progressively smaller as pregnancy advances, suggesting a progressive decline in circulatory reserve. If the data of Robbe66 are scrutinized carefully, a similar small increment in cardiac output in response to exercise is found to occur late in pregnancy. M-Mode echocardiography suggests that cardiac output increases secondary to increased fractional shortening early in pregnancy. Increase in left ventricular end-diastolic volume is the primary reason for increased cardiac output within pregnancy, however.67 Bruce and Johnson68 suggested that the decline in circulatory reserve is not related to impaired cardiac function but rather to peripheral pooling of blood resulting from the occlusion of the inferior vena cava by the uterus. There does not seem to be any appreciable buildup in oxygen debt during pregnancy when compared with nonpregnant controls.

The extent to which human uterine blood flow and oxygen consumption are altered by exercise during pregnancy is unclear. Studies considering the response of cardiac output to exercise suggest, however, that cardiac output is fixed and increases at a rate that parallels oxygen demand.12 Animal data have shown a reduction in uterine blood flow during exercise, accompanied by an increase in the maternal hematocrit. The augmented hemoglobin level enhances the blood oxygen-carrying capacity and serves to attenuate any possible reduction in oxygen delivery.69 Additionally, blood flow is redistributed within the uterus, and the uptake of oxygen by the uterus as a whole, and by the fetus, remains constant.70 It is likely that fetal oxygen consumption is unaffected during mild-to-moderate exercise in human pregnancy as well. Fetal heart tracings that were obtained from women during recovery from moderately strenuous exercise revealed no evidence of fetal distress (although a consistent fetal tachycardia was noted). This group of women also had fetal nonstress tests before and after exercise. All tests were reactive, and there was no significant difference in the monitoring time required to obtain a reactive nonstress test before and after exercise.71 The effect of exercise on the uterine artery blood flow velocity shows conflicting results with reports of no change and an increase and a decrease in systolic-to-diastolic ratios during maternal exercise.67

Back to Top
LABOR-INDUCED AND DELIVERY-INDUCED CHANGES

The hemodynamic responses to uterine contractions depend on the maternal posture in which they are studied. When measured in the supine position, a uterine contraction produces a 25% increase in cardiac output and a 15% decrease in heart rate. The resultant increment in stroke volume is 33%.72 If the same measurements are taken with the patient in lateral recumbency, the respective changes are only +7.6% (cardiac output), −0.7% (heart rate), and +7.7% (stroke volume). Pulse pressure while supine increases more than 26% in response to a contraction, whereas the increase is only 6% in lateral recumbency. There seems to be a remarkable degree of hemodynamic stability when the patient is on her side. Table 1 shows the similarities in peak hemodynamic values during a contraction in both positions studied. The significant differences between contractions are attributable to the inferior vena caval occlusion caused by the gravid uterus. In addition to venous obstruction, contractions while in the supine position produce complete occlusion of the distal aorta or the common iliac arteries73; the blood ejected by the left ventricle is distributed transiently only to the upper half of the vascular tree, resulting in an augmented response when measurements are taken in the upper extremities. Arterial pressure measurements obtained from the femoral artery while in the supine position during a contraction show a marked decrease.62 During contractions, there is a rise in central venous pressure and an increase in cardiopulmonary blood volume of approximately 300 to 500 mL.73,74

 

TABLE 1. Hemodynamic Measurements During a Contraction


Position

Cardiac Output (mL)

Pulse (beats/min)

Stroke Volume (mL)

Blood Pressure (mm Hg)

Supine

6522

79

79

132/79

Side

6830

84

81

126/80


Modified from Ueland K, Hansen JM: Maternal cardiovascular dynamics: II. Posture and uterine contractions. Am J Obstet Gynecol 103:1, 1969.

 

Anesthesia plays a significant role in modifying the cardiovascular response to labor and delivery. In a series of patients undergoing hemodynamic studies throughout labor and delivery, substantial differences were noted between the group receiving local and paracervical block anesthetics and the group receiving a caudal anesthetic (Table 2).75 In the patients receiving local and paracervical block anesthetics, the cardiac output increased progressively during labor and reached a peak value of 80% above supine prelabor values immediately after delivery. Heart rate showed little change, but stroke volume rose by approximately 75%. In the patients receiving a caudal anesthetic, the cardiac output remained relatively stable throughout the first stage of labor, increased only slightly during the second stage, and reached a peak value of 60% above supine prelabor values immediately after delivery. Anesthesia did not modify the profound changes accompanying delivery because the large increments in cardiac output for both groups from second stage to delivery were similar.

 

TABLE 2. Maternal Hemodynamics During Labor*


 

Early First Stage

Late First Stage

Second Stage

Post Partum

Immediately Type of Anesthesia

CO

P

SV

CO

P

SV

CO

P

SV

CO

P

SV

Caudal

11

−4

14

22

3

19

24

NC

23

59

1

54

Local

7

−7

17

25

−9

33

49

4

41

80

4

73


NC, no change; CO, cardiac output; P, pulse; SV, stroke volume.
*All values expressed as % change from supine prelabor and recorded between contractions.
Modified from Ueland K, Hansen JM: Maternal cardiovascular dynamics: III. Labor and delivery under local and caudal analgesia. Am J Obstet Gynecol 103:8, 1969.

 

The repetitive hemodynamic changes of uterine contraction during labor can be circumvented by cesarean section delivery. The significant increment in cardiac output accompanying delivery cannot be prevented, although it can be modified to some extent by the anesthetic technique employed. Table 3 summarizes the changes in hemodynamics associated with surgical delivery using spinal anesthesia, balanced general anesthesia (thiopental, succinylcholine, nitrous oxide), and epidural anesthesia with and without epinephrine.76,77,78,79

Some similarities should be stressed. The marked decrease in cardiac output and blood pressure after the induction of anesthesia was equivalent in the patients receiving a spinal anesthetic and in the patients receiving an epidural anesthetic with epinephrine.76,78 The hypotension was so profound in the latter group that 10 of the 12 patients required presurgical treatment to correct the blood pressure, which was not responsive to uterine displacement. In the balanced general anesthesia group,79 there was good hemodynamic stability throughout surgery except at the time of intubation and extubation and when awakening the patient postoperatively. During these procedures, there was a marked but transient elevation in cardiac output, heart rate, and blood pressure. The patients who received an epidural anesthetic without epinephrine76,78 showed remarkable hemodynamic stability throughout surgery and had the smallest increment in cardiac output at delivery, reaching only 25% above preanesthesia values.

The documented blood loss at vaginal delivery is approximately 500 mL, and the loss at cesarean section is approximately 1000 mL.35,36 The loss of this large volume of blood is well tolerated, owing in part to the hypervolemia of pregnancy and in part to the fact that there is a marked diminution in the vascular space at the time of delivery and that the lost volume is no longer needed. Table 4 summarizes the data of serial measurements of blood volume and hematocrit after delivery in a large number of patients.36 By the third postpartum day, the total decline in blood volume was similar for all patients, whether delivered vaginally or by cesarean section (16.2%). The only difference was found in the hematocrit values: The patients delivering vaginally had a 6% rise in hematocrit by the third postpartum day, whereas patients have cesarean section showed a decline of similar magnitude.

 

TABLE 3. Maternal Hemodynamics at Cesarean Section*


 

Anesthesia

Abdomen Open

Post Partum

10-min Post Partum

60-min Post Partum

Immediately After Type of Anesthesia

CO

P

SV

CO

P

SV

CO

P

SV

CO

P

SV

CO

P

SV

Spinal

−34

21

−44

2

7

1

56

−5

69

56

5

51

35

−5

41

Balanced general

7

7

2

25

−5

31

34

−11

48

41

−12

56

25

−16

47

Epidural − epinephrine

−6

8

−10

12

−5

18

25

7

18

21

−6

28

14

−7

27

Epidural + epinephrine

−17

6

−23

−2

NC

1

21

9

22

25

NC

17

12

NC

13


NC, no change; CO, cardiac output; P, pulse; SV, stroke volume.
*All values expressed as % change from supine preanesthesia values.
Data from Ueland K: Personal data; Ueland K, Akamatsu TJ, Eng M, et al: Maternal cardiovascular dynamics: VI. Cesarean section under epidural anesthesia without
epinephrine. Am J Obstet Gynecol 114:775, 1972; Ueland K, Gills RE, Hansen J: Maternal cardiovascular dynamics: I. Cesarean section under subarachnoid block anesthesia. Am J Obstet Gynecol 100:52, 1968; Ueland K, Hansen JM, Eng M, et al: Maternal cardiovascular dynamics: V. Cesarean section under thiopental, nitrous oxide, and succinylcholine anesthesia. Am J Obstet Gynecol 108:615, 1970.

 

 

TABLE 4. Postpartum Blood Volume and Hematocrit Changes*


 

10 min

60 min

1 Day

3 Days

5 Days

Type of Delivery

BV

Hct

BV

Hct

BV

Hct

BV

Hct

BV

Hct

Vagina

−7.2

2.6

−10.2

NC

−15.2

2.8

−16.2

5.2

  

Cesarean section

−14.4

NC

−17.4

−1.4

−16.5

−2.3

−16.2

−4.6

−19.3

−5.8


NC, no change; BV, blood volume; Hct, hematocrit.
*Values expressed as % change from predelivery values.
Modified from Ueland K: Maternal cardiovascular dynamics: IIV. Intrapartum blood volume changes. Am J Obstet Gynecol 126:671, 1976.

 

Back to Top
ACKNOWLEDGMENT

This chapter is dedicated in loving memory to Kent Ueland, MD, who was a wonderful physician, friend, and mentor.

Back to Top
REFERENCES

1. Lindhard J: über das Minutenvolum des Herzens bei Ruhe und bei Muskel-arbeit. Arch Physiol 161:233, 1915

2. Gammeltoft SA: Recherches sur le débit cardiaque par minute pendant la grossesse. Soc Biol 94:1099, 1926

3. Burwell CS: A comparison of the pressure in arm veins and femoral veins with specialreference to changes during pregnancy. Ann Intern Med 11:1305, 1938

4. Burwell CS, Strayhorn WD, Flickinger D, et al: Circulation during pregnancy. Arch Intern Med 62:979, 1938

5. Thornburg KL, Jacobson S, Giraud GD, Morton MJ: Hemodynamic changes in pregnancy. Semin Perinatol 24:11, 2000

6. Robson SC, Hunter S, Boys RJ, Dunlop W: Serial studies of factors influencing changes in cardiac output during human pregnancy. Am J Physiol 256:H1060, 1989

7. Clapp JF III, Capeless E: Cardiovascular function before, during, and after the first and subsequent pregnancies. Am J Cardiol 80:1469, 1997

8. Bader RA, Bader ME, Rose DJ, et al: Hemodynamics at rest and during exercise in normal pregnancy as studied by cardiac catheterization. J Clin Invest 34:1524, 1955

9. Ueland K, Novy MJ, Peterson EN, et al: Maternal cardiovascular dynamics: IV. The influence of gestational age on the maternal cardiovascular response to posture and exercise Am J Obstet Gynecol 104:856, 1969

10. Walters WAW, MacGregor WG, Hills M: Cardiac output at rest during pregnancy and the puerperium. Clin Sci 30:1, 1966

11. Lees MM, Taylor SH, Scott DB, et al: A study of cardiac output at rest throughout pregnancy. J Obstet Gynaecol Br Commonw 74:319, 1967

12. de Schwarcz SB, Aramendia P, Taquini AC: Variaciones hemodinamicas en el embarazo normal. Medicina 24:113, 1964

13. Adams JQ: Cardiovascular physiology in normal pregnancy: Studies with dye dilution technique. Am J Obstet Gynecol 67:741, 1954

14. Roy SB, Malkani RP, Virik R, et al: Circulatory effects of pregnancy. Am J Obstet Gynecol 96:221, 1966

15. vanOppen ACC, Stigter RH, Bruinse HW: Cardiac output in normal pregnancy: A critical review. Obstet Gynecol 87:310, 1996

16. Crapo RO: Normal cardiopulmonary physiology during pregnancy. Clin Obstet Gynecol 39:3, 1996

17. Hunter S, Robson SC: Adaptation of the maternal heart in pregnancy. Br Heart J 68:540, 1992

18. Hytten FE, Leitch I: The Physiology of Human Pregnancy. p24, 2nd ed. Oxford, Blackwell Scientific Publications, 1971

19. Pernoll ML, Metcalfe J, Schlenker TL, et al: Oxygen consumption at rest and during exercise in pregnancy. Respir Physiol 25:285, 1975

20. Elkus R, Popovich J Jr: Respiratory physiology in pregnancy. Clin Chest Med 13:555, 1992

21. Metcalfe J, Romney SL, Ramsey LH, et al: Estimation of uterine blood flow in normal human pregnancy at term. J Clin Invest 34:1632, 1955

22. Wulf KH, Kunzel W, Lehmann V: Clinical aspects ofplacental gas exchange. In Longo LD, Bartels H (eds): Respiratory Gas Exchange and Blood Flow in the Placenta. p 505, Bethesda, MD, US Department of Health, Education, and Welfare, DHEW Publication No. (NIH) 73-3611972

23. Burwell CS: Placenta as modified arteriovenous fistula, considered in relation to the circulatory adjustments to pregnancy. Am J Med Sci 195:1, 1938

24. Csapo A: Actomyosin formation by estrogen action. Am J Physiol 162:406, 1950

25. Burg JR, Dodek A, Kloster FE, et al: Alterations of systolic time intervals during pregnancy. Circulation 49:560, 1974

26. Tanz RD: Inotropic effects of certain steroids upon heart muscle. Rev Can Biol 22:147, 1963

27. Slater AJ, Gude N, Clarke IJ, et al: Haemodynamic changes and left ventricular performance during high-dose estrogen administration to male transsexuals. Br J Obstet Gynaecol 93:532, 1986

28. Gilson GJ, Samaan S, Crawford MH, et al: Changes in hemodynamics, ventricular remodeling, and ventricular increases during normal pregnancy: A longitudinal study. Obstet Gynecol 89:957, 1997

29. Geva T, Mauer MB, Striker L, et al: Effects of physiologic load of pregnancy on left ventricular decrease and remodeling. Am Heart J 133:53, 1997

30. Villablanca AC: Heart disease during pregnancy: Which cardiovascular changes are normal or transient? Postgrad Med 104:183, 1998

31. Poston L: Maternal vascular function in pregnancy. J Hum Hypertens 10:391, 1996

32. Weiner C, Thompson L: Nitric oxide and pregnancy. Semin Perinatol 21:367, 1997

33. Hata T, Ryukoh K, Fujiwaki R, et al: Effect of dehydroepiandrosterone sulfate on maternal cardiac function in term pregnancy. Am J Perinatol 13:11, 1996

34. Manabe A, Hata T, Yanagihara T, et al: Nitric oxide synthesis is increased after dehydroepiandrosterone sulphate administration in term human pregnancy. Hum Reprod 14:2116, 1999

35. Pritchard JA: Changes in the blood volume during pregnancy and delivery. Anesthesiology 26:393, 1965

36. Ueland K: Maternal cardiovascular dynamics: VII. Intrapartum blood volume changes Am J Obstet Gynecol 126:671, 1976

37. Chesley LC: Plasma and red cell volumes during pregnancy. Am J Obstet Gynecol 112:440, 1972

38. Lund CJ, Donovan JC: Blood volume during pregnancy: Significance of plasma and red cell volume. Am J Obstet Gynecol 98:393, 1967

39. Hytten FE, Paintin DB: Increase in plasma volume during normal pregnancy. J Obstet Gynaecol Br Commonw 70:402, 1963

40. Rovinsky JJ, Jaffin H: Cardiovascular hemodynamics in pregnancy: 1. Blood and plasma volumes in multiple pregnancy Am J Obstet Gynecol 93:1, 1965

41. Scott DE: Anemia in pregnancy. In Wynn RM (ed): Obstetrics and Gynecology Annual: 1972. p 219, New York, Appleton-Century-Crofts, 1972

42. O’Day MP: Cardio-respiratory physiological adaptation of pregnancy. Semin Perinatol 21:268, 1997

43. McFee JG: Anemia in pregnancy: A reappraisal. Obstet Gynecol Surv 28:769, 1973

44. Chisholm M: A controlled clinical trial of prophylactic folic acid and iron in pregnancy. J Obstet Gynaecol Br Commonw 73:191, 1966

45. Pritchard JA: Anemias complicating pregnancy and the puerperium. In Maternal Nutrition and the Course of Pregnancy. Committee on Maternal Nutrition/Food and Nutrition Board, National Research Council, National Academy of Sciences P 74, 1970

46. Chesley LC, Duffus GM: Posture and apparent plasma volume in late pregnancy. J Obstet Gynaecol Br Commonw 78:406, 1971

47. Croall J, Sherrif S, Matthews J: Nonpregnant maternal plasma volume and fetal growth retardation. Br J Obstet Gynaecol 85:90, 1978

48. Goodlin RC, Quaife MA, Dirksen JW: The significance, diagnosis, and treatment of maternal hypovolemia as associated with fetal/maternal illness. Semin Perinatol 5:163, 1981

49. Duvekot J, Cheriex E, Pieters F, et al: Maternal volume homeostasis in early pregnancy in relation to fetal growth restriction. Obstet Gynecol 85:361, 1995

50. Longo LD: Maternal blood volume and cardiac output during pregnancy: A hypothesis of endocrinologic control. Am J Physiol 245:R720, 1983

51. Burwell CS, Metcalfe J: Physiology and management. Heart Disease and Pregnancy. Boston, Little, Brown, 1958

52. Abramovich DR, Francis W, Helsby CR: Two cases of ruptured aneurysm of splanchnic arteries in pregnancy with comment on the lesser sac syndrome. J Obstet Gynaecol Br Commonw 76:1037, 1969

53. Donaldson JO: Neurology of Pregnancy. p 124, Philadelphia, WB Saunders, 1978

54. Manalo-Estrella P, Barker AE: Histopathologic findings in human aortic media associated with pregnancy. Arch Pathol 83:336, 1967

55. Cavanzo FJ, Taylor HB: Effect of pregnancy on human aorta and its relationship to dissecting aneurysms. Am J Obstet Gynecol 105:567, 1969

56. Ueland K, Parer JT: Effects of estrogens on the cardiovascular system of the ewe. Am J Obstet Gynecol 96:400, 1966

57. Walters WAW, Lim YL: Haemodynamic changes in women taking oral contraceptives. J Obstet Gynaecol Br Commonw 77:1007, 1970

58. Howard BK, Goodson JH, Mengert WF: Supine hypotensive syndrome in late pregnancy. Obstet Gynecol 1:371, 1953

59. Scott DB, Kerr MG: Inferior vena cava pressure in late pregnancy. J Obstet Gynaecol Br Commonw 70:1044, 1963

60. Kerr MG, Scott DB, Samuel E: Studies of the inferior vena cava in late pregnancy. BMJ 1:532, 1964

61. Schneider K-TM, Deckardt R: The implication of upright posture on pregnancy. J Perinatol Med 19:121, 1991

62. Bieniarz J, Grottogini JJ, Curachet E, et al: Aortocaval compression by the uterus in late human pregnancy: II. An arteriographic study Am J Obstet Gynecol 100:203, 1968

63. Knuttgen HG, Emerson K Jr: Physiological response to pregnancy at rest and during exercise. J Appl Physiol 36:549, 1974

64. Ueland K, Novy MJ, Metcalfe J: Cardiorespiratory responses to pregnancy and exercise in normal women and patients with heart disease. Am J Obstet Gynecol 115:4, 1973

65. Metcalfe J, McAnulty JH, Ueland K: The effects of pregnancy on the cardiovascular system and oxygentransport. Burwell and Metcalfe’s Heart Disease and Pregnancy, Physiology and Management. 2nd ed.. Boston, Little, Brown, 1986

66. Robbe H: Physical working capacity, blood volume and heart volume in cardiac patients during and after pregnancy. Acta Obstet Gynecol Scand 38:1, 1959

67. Veille J-C: Maternal and fetal cardiovascular response to exercise during pregnancy. Semin Perinatol 20:250, 1996

68. Bruce RA, Johnson WP: Exercise tolerance in pregnant cardiac patients. Clin Obstet Gynecol 4:665, 1961

69. Lotgering FK, Gilbert RD, Longo LD: Exercise responses in pregnant sheep: Oxygen consumption, uterine blood flow and blood volume. J Appl Physiol 55:834, 1983

70. Clapp JF III: Acute exercise stress in the pregnant ewe. Am J Obstet Gynecol 136:489, 1980

71. Hauth JC, Gilstrap LC, Widmer K: Fetal heart rate reactivity before and after maternal jogging during the third trimester. Am J Obstet Gynecol 142:545, 1982

72. Ueland K, Hansen JM: Maternal cardiovascular dynamics: II. Posture and uterine contractions Am J Obstet Gynecol 103:1, 1969

73. Hendricks CH: The hemodynamics of a uterine contraction. Am J Obstet Gynecol 76:969, 1958

74. Adams JQ, Alexander AM Jr: Alterations in cardiovascular physiology during labor. Obstet Gynecol 12:542, 1958

75. Ueland K, Hansen JM: Maternal cardiovascular dynamics: III. Labor and delivery under local and caudal analgesia Am J Obstet Gynecol 103:8, 1969

76. Ueland K: Unpublished data.

77. Ueland K, Akamatsu TJ, Eng M, et al: Maternal cardiovascular dynamics: VI. Cesarean section under epidural anesthesia without epinephrine Am J Obstet Gynecol 114:775, 1972

78. Ueland K, Gills RE, Hansen JM: Maternal cardiovascular dynamics: I. Cesarean section under subarachnoid block anesthesia Am J Obstet Gynecol 100:52, 1968

79. Ueland K, Hansen JM, Eng M, et al: Maternal cardiovascular dynamics: V. Cesarean section under thiopental,nitrous oxide, and succinylcholine anesthesia Am JObstet Gynecol 108:615, 1970

Back to Top