title: Chronic fetal placental embolization and hypoxemia cause hypertension and myocardial hypertrophy in fetal sheep.
abstract: To examine the cardiovascular effects on the fetus of an elevated umbilical vascular resistance resulting in fetal hypoxemia, we embolized the fetal side of the placenta in pregnant sheep and measured cardiovascular and hormonal changes and cellular growth in fetal heart. Chronically catheterized fetal sheep were embolized (n = 6) for 21 days between 0.74 and 0.88 of gestation into the descending aorta until arterial oxygen content was decreased by 40-50% of the preembolization value. Control animals (n = 6) received saline only. During embolization, fetuses became chronically hypoxemic (P < 0.001) and hypertensive (P < 0.001), with a progressive increase in umbilical artery resistance index (P < 0.001). There was also an increase in fetal plasma norepinephrine throughout the study period (P < 0.05). On day 21 of embolization, fetuses showed asymmetrical growth restriction, increased heart weight (P < 0.01), and increase in right and left ventricular wall thickness (P < 0.05) compared with control animals. The protein-to-DNA ratio, an index of cell size, increased in the right ventricular myocardium in the embolized group (P < 0.001), suggesting myocardial cell hypertrophy. We conclude that, during chronic placental damage leading to fetal hypoxemia with an increase in umbilical artery resistance index, fetuses developed arterial hypertension and asymmetrical growth restriction and that increases in afterload to the heart and plasma norepinephrine likely caused fetal myocardial hypertrophy.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Western Ontario, London, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Murotsuki
authors.forename: J R
authors.initials: JR
authors.lastname: Challis
authors.forename: V K
authors.initials: VK
authors.lastname: Han
authors.forename: L J
authors.initials: LJ
authors.lastname: Fraher
authors.forename: R
authors.initials: R
authors.lastname: Gagnon
mesh_terms: D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000209:etiology*; D002395:Catecholamines / Q000097:blood; D004247:DNA / Q000378:metabolism; D005260:Female; D005312:Fetal Blood; D005315:Fetal Diseases / Q000209:etiology*; D005333:Fetus / Q000502:physiology; D005740:Gases / Q000097:blood; D006340:Heart Rate, Fetal; D006973:Hypertension / Q000209:etiology*; D000860:Hypoxia / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D008863:Microspheres; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D012039:Regional Blood Flow; D012756:Sheep / Q000196:embryology; D013997:Time Factors; D014469:Umbilical Arteries / Q000502:physiology
chemical_list: D002395:Catecholamines; D005740:Gases; D004247:DNA