We tested the hypothesis that fetal pulmonary arterial circulation reacts to changes in fetal oxygenation status at near-term gestation.
Study Design:
A total of 20 rhesus macaques underwent fetal Doppler ultrasonography at near-term gestation. Right pulmonary artery (RPA), umbilical artery (UA), ductus arteriosus (DA), and ductus venosus (DV) blood velocity waveforms were obtained, and pulsatility index (PI) values were calculated. Fetal right and left ventricular cardiac outputs were determined. Ultrasonographic data were collected during 3 maternal oxygenation states: room air (baseline), hyperoxemia, and hypoxemia.
Results:
Fetal RPA PI values increased (P < .05) during maternal hypoxemia and decreased (P < .05) during maternal hyperoxemia, compared with baseline. Maternal hyperoxemia increased (P < .05) DA PI values from baseline. Fetal cardiac outputs, UA, and DV PI values were not affected.
Conclusions:
Our results demonstrate that at near-term gestation, fetal pulmonary arterial circulation is a dynamic vascular bed that reflects acute and short-term changes in fetal oxygenation.
CohnHESacksEJHeymannMARudolphAM. Cardiovascular responses to hypoxemia and acidemia in fetal lambs. Am J Obstet Gynecol. 1974;120(6):817–824.
2.
HansonMA. Do we now understand the control of the fetal circulation?Eur J Obstet Gynecol Reprod Biol. 1997;75(1):55–61.
3.
SignoreCFreemanRKSpongCY. Antenatal testing-a reevaluation: executive summary of a Eunice Kennedy Shriver National Institute of Child Health and Human Development workshop. Obstet Gynecol. 2009;113(3):687–701.
4.
BraceRACheungCYDavisLEGagnonRHardingRWidnessJA. Sources of amniotic fluid erythropoietin during normoxia and hypoxia in fetal sheep. Am J Obstet Gynecol. 2006;195(1):246–254.
5.
LoukovaaraMTeramoKAlfthanHHamalainenEStefanovicVAnderssonS. Amniotic fluid S100B protein and erythropoietin in pregnancies at risk for fetal hypoxia. Eur J Obstet Gynecol Reprod Biol. 2009;142(2):115–118.
6.
BuescherUHertwigKWolfCDudenhausenJW. Erythropoietin in amniotic fluid as a marker of chronic fetal hypoxia. Int J Gynaecol Obstet. 1998;60(3):257–263.
7.
RasanenJWoodDCDebbsRHCohenJWeinerSHuhtaJC. Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy: a randomized study. Circulation. 1998;97(3):257–262.
8.
MorinFCEganEAFergusonWLundgrenCE. Development of pulmonary vascular response to oxygen. Am J Physiol. 1988;254(3 pt 2):H542–H546.
9.
MorinFCEganEA. Pulmonary hemodynamics in fetal lambs during development at normal and increased oxygen tension. J Appl Physiol. 1992;73(1):213–218.
10.
MakikallioKErkinaroTNiemiN. Fetal oxygenation and Doppler ultrasonography of cardiovascular hemodynamics in a chronic near-term sheep model. Am J Obstet Gynecol. 2006;194(2):542–550.
11.
LewisABHeymannMARudolphAM. Gestational changes in pulmonary vascular responses in fetal lambs in utero. Circ Res. 1976;39(4):536–541.
12.
GaoYRajJU. Regulation of the pulmonary circulation in the fetus and newborn. Physiol Rev. 2010;90(4):1291–1335.
13.
FinemanJRSoiferSJHeymannMA. Regulation of pulmonary vascular tone in the perinatal period. Annu Rev Physiol. 1995;57:115–134.
14.
KiserudT. Physiology of the fetal circulation. Semin Fetal Neonatal Med. 2005;10(6):493–503.
15.
LevinDLRudolphAMHeymannMAPhibbsRH. Morphological development of the pulmonary vascular bed in fetal lambs. Circulation. 1976;53(1):144–151.
RasanenJWoodDCWeinerSLudomirskiAHuhtaJC. Role of the pulmonary circulation in the distribution of human fetal cardiac output during the second half of pregnancy. Circulation. 1996;94(5):1068–1073.
20.
SafarMELevyBIStruijker-BoudierH. Current perspectives on arterial stiffness and pulse pressure in hypertension and cardiovascular diseases. Circulation. 2003;107(22):2864–2869.
21.
BlackSMJohengenMJMaZDBristowJSoiferSJ. Ventilation and oxygenation induce endothelial nitric oxide synthase gene expression in the lungs of fetal lambs. J Clin Invest. 1997;100(6):1448–1458.
22.
UematsuMOharaYNavasJP. Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol. 1995;269(6 pt 1):C1371–C1378.
23.
ShaulPWYuhannaISGermanZChenZSteinhornRHMorinFC. Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension. Am J Physiol. 1997;272(5 pt 1):L1005–L1012.
24.
SteudelWIchinoseFHuangPL. Pulmonary vasoconstriction and hypertension in mice with targeted disruption of the endothelial nitric oxide synthase (NOS 3) gene. Circ Res. 1997;81(1):34–41.
25.
IbeBORajJU. Endogenous arachidonic acid metabolism by calcium ionophore stimulated ferret lungs. Effect of age, hypoxia. Lab Invest. 1992;66(3):370–377.
26.
MorrowRJAdamsonSLBullSBRitchieJW. Acute hypoxemia does not affect the umbilical artery flow velocity waveform in fetal sheep. Obstet Gynecol. 1990;75(4):590–593.
27.
MorrowRJAdamsonSLBullSBRitchieJW. Effect of placental embolization on the umbilical arterial velocity waveform in fetal sheep. Am J Obstet Gynecol. 1989;161(4):1055–1060.
28.
TchirikovMEisermannKRybakowskiCSchroderHJ. Doppler ultrasound evaluation of ductus venosus blood flow during acute hypoxemia in fetal lambs. Ultrasound Obstet Gynecol. 1998;11(6):426–431.
29.
KiserudTOzakiTNishinaHRodeckCHansonMA. Effect of NO, phenylephrine, and hypoxemia on ductus venosus diameter in fetal sheep. Am J Physiol Heart Circ Physiol. 2000;279(3):H1166–H1171.
30.
NicolaidesKHCampbellSBradleyRJBilardoCMSoothillPWGibbD. Maternal oxygen therapy for intrauterine growth retardation. Lancet. 1987;329(8539):942–945.
31.
SchmidtKGDi TommasoMSilvermanNHRudolphAM. Doppler echocardiographic assessment of fetal descending aortic and umbilical blood flows. Validation studies in fetal lambs. Circulation. 1991;83(5):1731–1737.
