AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 3
July 1990
LEFT VENTRICULAR STROKE VOLUME AND OUTPUT IN HEALTHY TERM INFANTS Per Winberg, M.D., and Bo RW. Lundell, M.D.
ABSTRACT
In the human adult, cardiac output is regulated by simultaneous changes in stroke volume (SV) and heart rate (HR). The fetal myocardium differs from the adult's both structurally and functionally.1 The ability to increase SV with increasing preload has been demonstrated to be limited in fetal lambs due to low diastolic compliance.23 Thus, the fetal myocardium seems to function at the peak of a FrankStarling curve and HR has accordingly been suggested to be the main determinant of output in the fetus and newborn.4 The postnatal circulatory transition involves fundamental circulatory changes. The placental circulation is disconnected, leading to increased systemic vascular resistance (SVR). The pulmonary vascular resistance decreases, promoting a left-to-right shunt through the open ductus arteriosus. As long as the ductus is open, the falling pulmonary vascular resistance is incorporated in the total afterload resistance seen by the left ventricle. Hence, the physiologic ductus shunt will cause substantial changes in left ventricular afterload resistance during the postnatal transition. Noninvasive ultrasound imaging and Doppler techniques permit studies of central hemodynamics
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
Left ventricular output, left ventricular stroke volume, and systemic vascular resistance were measured noninvasively in 16 healthy term infants at 6 predefined time intervals from less than 15 minutes to 72 hours after birth. The blood flow velocity in the ascending aorta was measured by range-gated Doppler technique and multiplied by the cross-sectional area, measured by 2-dimensional and M-mode echocardiography to yield left ventricular output. Stroke volume was calculated by dividing left ventricular output by heart rate. Mean arterial blood pressure was measured by oscillometric technique and used for calculation of systemic vascular resistance. A poor association between heart rate and left ventricular output was found, whereas there was a very close relationship between stroke volume and left ventricular output. There was also a reciprocal relationship between systemic vascular resistance and stroke volume. This suggests that stroke volume and not heart rate is the main determinant of neonatal left ventricular output and that the low postnatal afterload might strengthen this relationship.
in newborn infants. The aim of this study was to investigate the relationships between left ventricular output (LVO), SV, HR, and SVR during the neonatal circulatory transition. MATERIAL AND METHODS
Sixteen term infants delivered by elective cesarean section were studied. LVO was measured according to the method first described in infants by Alverson et al.5 The blood flow velocity in the ascending aorta was recorded using a range-gated Doppler velocimeter (ALFRED, Vingmed A/S, Oslo, Norway), and a 5 MHz transducer placed in the suprasternal notch. The space-average velocity (the average over the cross-section of the aorta) and the meanflowvelocity (the temporal mean of the space-average velocity) signals were recorded on an oscillograph. The mean flow velocity was averaged over 20 to 30 consecutive beats, from a stable recording with the highest amplitude. 2-Dimensional and M-mode echocardiography was performed immediately after each Doppler re-
Department of Pediatrics, Karolinska Institute, Sachs's Children's Hospital, and St. Goran's Children's Hospital, Stockholm, Sweden This study was supported by the General Maternity Hospital Foundation, the Swedish Society for Medicine, and Sallskapet Barnavard Reprint requests: Dr. Winberg, Sachs Children's Hospital, Sachsgatan 1, S-116 69 Stockholm, Sweden Copyright © 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
223
AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 3
LVO I x min x m
100
120
140
160
180
HR Figure 1. Heart rate (HR) versus left ventricular output (LVO) in 16 term infants during the first 72 hours after birth.
8 • 7
6
LVO
c: \j
x min x rri2
4
RESULTS
All infants were healthy, had normal Apgar scores, and an apparently normal cardiopulmonary transition. Gestational age was 38.5 (0.7) weeks (mean and 1 SD) and birthweight was 3370 (344) gm. Recordings were obtained at all occasions in every infant. LVO, SV, HR, and SVR are presented in Table 1. In spite of a fall in HR between 30 minutes and 2 hours (p < 0.01), LVO remained unchanged, due to a concomitant increase in SV (p < 0.01). Between 2 and 24 hours, HR did not change, whereas a 24% decrease in LVO (p < 0.01) was associated with a 23% decrease in SV (p < 0.01). This indicates that SV is more important to LVO than HR. The relationships HR-LVO and SV-LVO are shown in Figures 1 and 2, respectively. The relative changes in LVO and
Table 1.
Age < 1 5 min 30 min 2 hr 5 hr 24 hr 72 hr
± ± ± ± ± ±
2
10
20
30 O V
40
50
ml x m
Figure 2. Left ventricular stroke volume (SV) versus left ventricular output (LVO) in 16 term infants the first 72 hours after birth.
Hemodynamic Changes in 16 Term Infants the First 72 Hours After Birth*
LVO (l/min m?)
3.81 3.94 3.85 3.31 2.94 2.99
yip *
3
0.8 1.2 0.8 0.8 0.6 0.7
SV (mllrn*)
25.3 26.6 29.2 27.6 22.5 24.6
± ± ± ± ± ±
4.1 7.6 7.2 6.4 4.5 6.4
HR (bpm) 150 148 133 121 131 124
± ± ± ± ± ±
17 12 11 14 11 18
BPm (mmHg)
45.3 ± 47.9 ± 45.1 ± 49.8 ± 52.0 ± 56. 9±
7 7 6 4 8 7
SVR (mmHg min milliter)
12.3 13.5 12.3 15.8 18.3 19.9
± ± ± ± ± ±
3.7 5.8 2.8 3.9 4.5 4.9
*Meanand 1 SD. LVO: left ventricular output; SV: left ventricular stroke volume; HR: heart rate; BPm: mean arterial blood pressure; SVR: 224 systemic vascular resistance.
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
cording, using a 7.5 MHz sector scanner and an echocardiograph (Technicare, Denver, CO). The end-systolic internal diameter (trailing edge to leading edge) of the ascending aorta, 5 to 10 mm above the valves, was determined from a hard copy of the parasternal long axis M-mode recording, and averaged over 8 to 10 consecutive heart beats. The calculated cross-sectional area was multiplied by the mean flow velocity and divided by the body surface area, to give LVO in 1 X min" 1 x m~2. Stroke volume was calculated by dividing LVO by HR measured from the Doppler recording. Arterial blood pressure (BP) was measured with a cuff on the right upper arm in connection with each recording, using the oscillometric technique6 (Omega 1400, In Vivo Research Laboratory, Broken Arrow, OK). Mean BP was divided by LVO, to get systemic vascular resistance in mmHg X l-i x min x m2. All recordings in the same infant were made by the same investigator and were performed immediately after birth and 30 minutes, 2, 5, 24, and 72 hours later. The study was approved by the local Committee of Ethics, and informed consent from the parents was obtained prior to the delivery. The statistical evaluation was made by multifactorial analysis of variance, and Tukey's Honestly Significant Difference test was used for multiple comparisons of means.7 Linear regression was only used to analyze the relationship between HR and LVO, since these were the only variables that were measured independently of each other.
July 1990
NEONATAL LVO AND STROKE VOLUME/Winberg, Lundell
HR between consecutive measurements are shown in Figure 3, and the corresponding changes in LVO and SV, in Figure 4. The figures demonstrate the close LVO-SV relationship and the poor HR-LVO relationship. Using regression analysis, a weak HR-LVO relationship was found (r = 0.33, p < 0.05), but no relationship between relative changes in HR and LVO could be established (r = 0.07, p = 0.05). In Figure 5 a reciprocal relationship between SVR and SV is demonstrated.
SV ml x rfi 60
50 40 30
DISCUSSION 20 10
10
t
100
o
20
25
30
35
SVR
•
50
15
mmHg x 1 x min x m Figure 5. Left ventricular stroke volume (SV) versus systemic vascular resistance (SVR) in 16 term infants the first 72 hours after birth.
•
ctJ
O
o -50
•
i
i
-20
0 % HR change
20
Figure 3. Relative changes in heart rate (HR) and left ventricular output (LVO) in consecutive measurements in 16 term infants the first 72 hours after birth.
100
o
•
50
CO
o O 0
-50
waBm
•
• I
-50
50
.
I
,
100
% SV change Figure 4. Relative changes in left ventricular stroke volume (SV) and left ventricular output (LVO) in consecutive measurements in 16 term infants the first 72 hours after birth.
eral studies in newborn infants with good results.5'8-9 It can be concluded from these studies that the product of cross-sectional mean flow velocity and the cross-sectional area derived from the inner diameter should yield an accurate measure of output. With the Doppler method, SV is calculated from the measured LVO. Thus, an over- or underestimation of LVO directly affects SV in the same direction, and the relationship between LVO and SV might accordingly be overemphasized. However this problem also afflicts the invasive methods. The finding that LVO changes are mainly secondary to changes in SV differs from the general comprehension that HR is the most important determinant of fetal and neonatal LVO. In our study, though, long-term changes were analyzed, and not beat to beat or short-term changes, where HR might be of more importance. The concept of HR as the main determinant of LVO has, however, been questioned.10-12 Ultrasound Doppler studies in the human fetus with cardiac arrhythmias have demonstrated a substantial ability of the heart to vary SV.1011 In a recent study in preterm lambs with patent ductus arteriosus, significant changes in LVO were seen without changes in HR.12 SVR calculated from mean BP and LVO will not only measure the resistance in the systemic circulation, but also it will reflect the resistance in the ductus and pulmonary circulation as long as the ductus remains open. It is, accordingly, a measure of the total afterload resistance seen by the left ventricle. The inverse correlation between SVR and SV (Fig. 5) suggests that vascular conductance is an important factor for left ventricular performance in the neo- 225
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
The ultrasound Doppler technique is strictly noninvasive and a minimum of stress is inflicted on the infants. The method has been validated in sev-
nate. The importance of SVR for fetal LVO is previously known,13 and in preterm lambs with patent ductus arteriosus12 a relationship between low SVR and high SV has been demonstrated. In patent ductus arteriosus the combination of high diastolic filling and low SVR might enhance left ventricular performance. Ductus shunting was not measured in our study. The changes in SVR and SV during the first day might, however, be explained by the physiologic ductus shunt, which is known to appear at this time.14-15 The peak in SV at 2 hours after birth at the same time as SVR reaches its lowest value thus suggests a maximal left-to-right ductus shunt. The findings in this study indicate that LVO during the postnatal circulatory transition in the healthy neonate is mainly regulated through changes in SV and not HR. We also find left ventricular afterload resistance an important determinant of SV The low postnatal afterload might accordingly have contributed to the strong relationship between LVO and SV. REFERENCES
1. Fisher J, Towbin J: Maturation of the heart. Clin Perinatol 15:421-446, 1988 2. Friedman WF: The intrinsic physiologic properties of the developing heart. Prog Cardiovasc Dis 15:87—111, 1972 3. Friedman WF, Kirkpatrick SE: In situ physiological study of the developing heart. Recent Adv Stud Cardiac Struct Metab 5:497-504, 1975 4. Rudolph AM, Heyman MA: Cardiac output in the fetal lamb: The effect of spontaneous and induced changes of
226
5.
6. 7. 8.
9.
10.
11. 12. 13. 14. 15.
July 1990
heart rate on right and left ventricular output. Am J Obstet Gynecol 124:183-192, 1976 Alverson DC, Eldridge MW, Dillon T, Yabek SM, Berman W: Noninvasive pulsed Doppler determination of cardiac output in neonates and children. J Pediatr 101:46— 50, 1982 Sonesson S-E, Broberger U: Arterial blood pressure in the very low birth weight neonate. Acta Paediatr Scand 76:338-341, 1987 Daniel W: Biostatistics: A foundation for analysis in the health sciences, 3rd ed. New York: John Wiley & Sons, 1983, pp 224-226 Goldberg S, Sahn D, Allen H, Valdes-Cruz L, Hoenecke H, Carnahan Y: Evaluation of pulmonary and systemic bloodflowby 2-dimensional Doppler echocardiography using fast Fourier transform spectral analysis. Am J Cardiol 50:1394-1400, 1982 Mellander M, Sabel K-G, Caidahl K, Solymar L, Eriksson B: Doppler determination of cardiac output in infants and children: Comparison with simultaneous thermodilution. Pediatr Cardiol 8:241-246, 1987 Marsal K, Eik-Nes SH, Persson P-H, Ulstein M: Blood flow in human fetal aorta in normal pregnancy and in fetal cardiac arrhythmia. Acta Obstet Gynecol Scand Suppl 93:39, 1980 Tonge HM, Stewart PA, Wladimiroff JW: Fetal blood flow measurements during fetal cardiac arrhythmia. Early Hum Dev 10:23-34, 1984 Clyman RI, Mauray F, Heyman MA, Roman C: Cardiovascular effects of patent ductus arteriosus in preterm lambs with respiratory distress. J Pediatr 111:579-587, 1987 Gilbert RD: Effects of afterload and baroreceptors on cardiac function in fetal sheep. J Dev Physiol 4:299, 1982 Gessner I, Krovetz LJ, Bensin RW, Prystowsky H, Stenger V, Eitzman DV: Hemodynamic adaptions in the newborn infant. Pediatrics 36:752-762, 1965 Hiraishi S, Misawa H, Oguchi K, et al: Two-dimensional Doppler echocardiographic assessment of closure of the ductus arteriosus in normal newborn infants. J Pediatr 111:755-760, 1987
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 3
July 1990
LEFT VENTRICULAR STROKE VOLUME AND OUTPUT IN HEALTHY TERM INFANTS Per Winberg, M.D., and Bo RW. Lundell, M.D.
ABSTRACT
In the human adult, cardiac output is regulated by simultaneous changes in stroke volume (SV) and heart rate (HR). The fetal myocardium differs from the adult's both structurally and functionally.1 The ability to increase SV with increasing preload has been demonstrated to be limited in fetal lambs due to low diastolic compliance.23 Thus, the fetal myocardium seems to function at the peak of a FrankStarling curve and HR has accordingly been suggested to be the main determinant of output in the fetus and newborn.4 The postnatal circulatory transition involves fundamental circulatory changes. The placental circulation is disconnected, leading to increased systemic vascular resistance (SVR). The pulmonary vascular resistance decreases, promoting a left-to-right shunt through the open ductus arteriosus. As long as the ductus is open, the falling pulmonary vascular resistance is incorporated in the total afterload resistance seen by the left ventricle. Hence, the physiologic ductus shunt will cause substantial changes in left ventricular afterload resistance during the postnatal transition. Noninvasive ultrasound imaging and Doppler techniques permit studies of central hemodynamics
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
Left ventricular output, left ventricular stroke volume, and systemic vascular resistance were measured noninvasively in 16 healthy term infants at 6 predefined time intervals from less than 15 minutes to 72 hours after birth. The blood flow velocity in the ascending aorta was measured by range-gated Doppler technique and multiplied by the cross-sectional area, measured by 2-dimensional and M-mode echocardiography to yield left ventricular output. Stroke volume was calculated by dividing left ventricular output by heart rate. Mean arterial blood pressure was measured by oscillometric technique and used for calculation of systemic vascular resistance. A poor association between heart rate and left ventricular output was found, whereas there was a very close relationship between stroke volume and left ventricular output. There was also a reciprocal relationship between systemic vascular resistance and stroke volume. This suggests that stroke volume and not heart rate is the main determinant of neonatal left ventricular output and that the low postnatal afterload might strengthen this relationship.
in newborn infants. The aim of this study was to investigate the relationships between left ventricular output (LVO), SV, HR, and SVR during the neonatal circulatory transition. MATERIAL AND METHODS
Sixteen term infants delivered by elective cesarean section were studied. LVO was measured according to the method first described in infants by Alverson et al.5 The blood flow velocity in the ascending aorta was recorded using a range-gated Doppler velocimeter (ALFRED, Vingmed A/S, Oslo, Norway), and a 5 MHz transducer placed in the suprasternal notch. The space-average velocity (the average over the cross-section of the aorta) and the meanflowvelocity (the temporal mean of the space-average velocity) signals were recorded on an oscillograph. The mean flow velocity was averaged over 20 to 30 consecutive beats, from a stable recording with the highest amplitude. 2-Dimensional and M-mode echocardiography was performed immediately after each Doppler re-
Department of Pediatrics, Karolinska Institute, Sachs's Children's Hospital, and St. Goran's Children's Hospital, Stockholm, Sweden This study was supported by the General Maternity Hospital Foundation, the Swedish Society for Medicine, and Sallskapet Barnavard Reprint requests: Dr. Winberg, Sachs Children's Hospital, Sachsgatan 1, S-116 69 Stockholm, Sweden Copyright © 1990 by Thieme Medical Publishers, Inc., 381 Park Avenue South, New York, NY 10016. All rights reserved.
223
AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 3
LVO I x min x m
100
120
140
160
180
HR Figure 1. Heart rate (HR) versus left ventricular output (LVO) in 16 term infants during the first 72 hours after birth.
8 • 7
6
LVO
c: \j
x min x rri2
4
RESULTS
All infants were healthy, had normal Apgar scores, and an apparently normal cardiopulmonary transition. Gestational age was 38.5 (0.7) weeks (mean and 1 SD) and birthweight was 3370 (344) gm. Recordings were obtained at all occasions in every infant. LVO, SV, HR, and SVR are presented in Table 1. In spite of a fall in HR between 30 minutes and 2 hours (p < 0.01), LVO remained unchanged, due to a concomitant increase in SV (p < 0.01). Between 2 and 24 hours, HR did not change, whereas a 24% decrease in LVO (p < 0.01) was associated with a 23% decrease in SV (p < 0.01). This indicates that SV is more important to LVO than HR. The relationships HR-LVO and SV-LVO are shown in Figures 1 and 2, respectively. The relative changes in LVO and
Table 1.
Age < 1 5 min 30 min 2 hr 5 hr 24 hr 72 hr
± ± ± ± ± ±
2
10
20
30 O V
40
50
ml x m
Figure 2. Left ventricular stroke volume (SV) versus left ventricular output (LVO) in 16 term infants the first 72 hours after birth.
Hemodynamic Changes in 16 Term Infants the First 72 Hours After Birth*
LVO (l/min m?)
3.81 3.94 3.85 3.31 2.94 2.99
yip *
3
0.8 1.2 0.8 0.8 0.6 0.7
SV (mllrn*)
25.3 26.6 29.2 27.6 22.5 24.6
± ± ± ± ± ±
4.1 7.6 7.2 6.4 4.5 6.4
HR (bpm) 150 148 133 121 131 124
± ± ± ± ± ±
17 12 11 14 11 18
BPm (mmHg)
45.3 ± 47.9 ± 45.1 ± 49.8 ± 52.0 ± 56. 9±
7 7 6 4 8 7
SVR (mmHg min milliter)
12.3 13.5 12.3 15.8 18.3 19.9
± ± ± ± ± ±
3.7 5.8 2.8 3.9 4.5 4.9
*Meanand 1 SD. LVO: left ventricular output; SV: left ventricular stroke volume; HR: heart rate; BPm: mean arterial blood pressure; SVR: 224 systemic vascular resistance.
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
cording, using a 7.5 MHz sector scanner and an echocardiograph (Technicare, Denver, CO). The end-systolic internal diameter (trailing edge to leading edge) of the ascending aorta, 5 to 10 mm above the valves, was determined from a hard copy of the parasternal long axis M-mode recording, and averaged over 8 to 10 consecutive heart beats. The calculated cross-sectional area was multiplied by the mean flow velocity and divided by the body surface area, to give LVO in 1 X min" 1 x m~2. Stroke volume was calculated by dividing LVO by HR measured from the Doppler recording. Arterial blood pressure (BP) was measured with a cuff on the right upper arm in connection with each recording, using the oscillometric technique6 (Omega 1400, In Vivo Research Laboratory, Broken Arrow, OK). Mean BP was divided by LVO, to get systemic vascular resistance in mmHg X l-i x min x m2. All recordings in the same infant were made by the same investigator and were performed immediately after birth and 30 minutes, 2, 5, 24, and 72 hours later. The study was approved by the local Committee of Ethics, and informed consent from the parents was obtained prior to the delivery. The statistical evaluation was made by multifactorial analysis of variance, and Tukey's Honestly Significant Difference test was used for multiple comparisons of means.7 Linear regression was only used to analyze the relationship between HR and LVO, since these were the only variables that were measured independently of each other.
July 1990
NEONATAL LVO AND STROKE VOLUME/Winberg, Lundell
HR between consecutive measurements are shown in Figure 3, and the corresponding changes in LVO and SV, in Figure 4. The figures demonstrate the close LVO-SV relationship and the poor HR-LVO relationship. Using regression analysis, a weak HR-LVO relationship was found (r = 0.33, p < 0.05), but no relationship between relative changes in HR and LVO could be established (r = 0.07, p = 0.05). In Figure 5 a reciprocal relationship between SVR and SV is demonstrated.
SV ml x rfi 60
50 40 30
DISCUSSION 20 10
10
t
100
o
20
25
30
35
SVR
•
50
15
mmHg x 1 x min x m Figure 5. Left ventricular stroke volume (SV) versus systemic vascular resistance (SVR) in 16 term infants the first 72 hours after birth.
•
ctJ
O
o -50
•
i
i
-20
0 % HR change
20
Figure 3. Relative changes in heart rate (HR) and left ventricular output (LVO) in consecutive measurements in 16 term infants the first 72 hours after birth.
100
o
•
50
CO
o O 0
-50
waBm
•
• I
-50
50
.
I
,
100
% SV change Figure 4. Relative changes in left ventricular stroke volume (SV) and left ventricular output (LVO) in consecutive measurements in 16 term infants the first 72 hours after birth.
eral studies in newborn infants with good results.5'8-9 It can be concluded from these studies that the product of cross-sectional mean flow velocity and the cross-sectional area derived from the inner diameter should yield an accurate measure of output. With the Doppler method, SV is calculated from the measured LVO. Thus, an over- or underestimation of LVO directly affects SV in the same direction, and the relationship between LVO and SV might accordingly be overemphasized. However this problem also afflicts the invasive methods. The finding that LVO changes are mainly secondary to changes in SV differs from the general comprehension that HR is the most important determinant of fetal and neonatal LVO. In our study, though, long-term changes were analyzed, and not beat to beat or short-term changes, where HR might be of more importance. The concept of HR as the main determinant of LVO has, however, been questioned.10-12 Ultrasound Doppler studies in the human fetus with cardiac arrhythmias have demonstrated a substantial ability of the heart to vary SV.1011 In a recent study in preterm lambs with patent ductus arteriosus, significant changes in LVO were seen without changes in HR.12 SVR calculated from mean BP and LVO will not only measure the resistance in the systemic circulation, but also it will reflect the resistance in the ductus and pulmonary circulation as long as the ductus remains open. It is, accordingly, a measure of the total afterload resistance seen by the left ventricle. The inverse correlation between SVR and SV (Fig. 5) suggests that vascular conductance is an important factor for left ventricular performance in the neo- 225
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
The ultrasound Doppler technique is strictly noninvasive and a minimum of stress is inflicted on the infants. The method has been validated in sev-
nate. The importance of SVR for fetal LVO is previously known,13 and in preterm lambs with patent ductus arteriosus12 a relationship between low SVR and high SV has been demonstrated. In patent ductus arteriosus the combination of high diastolic filling and low SVR might enhance left ventricular performance. Ductus shunting was not measured in our study. The changes in SVR and SV during the first day might, however, be explained by the physiologic ductus shunt, which is known to appear at this time.14-15 The peak in SV at 2 hours after birth at the same time as SVR reaches its lowest value thus suggests a maximal left-to-right ductus shunt. The findings in this study indicate that LVO during the postnatal circulatory transition in the healthy neonate is mainly regulated through changes in SV and not HR. We also find left ventricular afterload resistance an important determinant of SV The low postnatal afterload might accordingly have contributed to the strong relationship between LVO and SV. REFERENCES
1. Fisher J, Towbin J: Maturation of the heart. Clin Perinatol 15:421-446, 1988 2. Friedman WF: The intrinsic physiologic properties of the developing heart. Prog Cardiovasc Dis 15:87—111, 1972 3. Friedman WF, Kirkpatrick SE: In situ physiological study of the developing heart. Recent Adv Stud Cardiac Struct Metab 5:497-504, 1975 4. Rudolph AM, Heyman MA: Cardiac output in the fetal lamb: The effect of spontaneous and induced changes of
226
5.
6. 7. 8.
9.
10.
11. 12. 13. 14. 15.
July 1990
heart rate on right and left ventricular output. Am J Obstet Gynecol 124:183-192, 1976 Alverson DC, Eldridge MW, Dillon T, Yabek SM, Berman W: Noninvasive pulsed Doppler determination of cardiac output in neonates and children. J Pediatr 101:46— 50, 1982 Sonesson S-E, Broberger U: Arterial blood pressure in the very low birth weight neonate. Acta Paediatr Scand 76:338-341, 1987 Daniel W: Biostatistics: A foundation for analysis in the health sciences, 3rd ed. New York: John Wiley & Sons, 1983, pp 224-226 Goldberg S, Sahn D, Allen H, Valdes-Cruz L, Hoenecke H, Carnahan Y: Evaluation of pulmonary and systemic bloodflowby 2-dimensional Doppler echocardiography using fast Fourier transform spectral analysis. Am J Cardiol 50:1394-1400, 1982 Mellander M, Sabel K-G, Caidahl K, Solymar L, Eriksson B: Doppler determination of cardiac output in infants and children: Comparison with simultaneous thermodilution. Pediatr Cardiol 8:241-246, 1987 Marsal K, Eik-Nes SH, Persson P-H, Ulstein M: Blood flow in human fetal aorta in normal pregnancy and in fetal cardiac arrhythmia. Acta Obstet Gynecol Scand Suppl 93:39, 1980 Tonge HM, Stewart PA, Wladimiroff JW: Fetal blood flow measurements during fetal cardiac arrhythmia. Early Hum Dev 10:23-34, 1984 Clyman RI, Mauray F, Heyman MA, Roman C: Cardiovascular effects of patent ductus arteriosus in preterm lambs with respiratory distress. J Pediatr 111:579-587, 1987 Gilbert RD: Effects of afterload and baroreceptors on cardiac function in fetal sheep. J Dev Physiol 4:299, 1982 Gessner I, Krovetz LJ, Bensin RW, Prystowsky H, Stenger V, Eitzman DV: Hemodynamic adaptions in the newborn infant. Pediatrics 36:752-762, 1965 Hiraishi S, Misawa H, Oguchi K, et al: Two-dimensional Doppler echocardiographic assessment of closure of the ductus arteriosus in normal newborn infants. J Pediatr 111:755-760, 1987
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
AMERICAN JOURNAL OF PERINATOLOGY/VOLUME 7, NUMBER 3
