CHRONIC FETAL-PLACENTAL EMBOLIZATION AND HYPOXEMIA CAUSE HYPERTENSIONAND MYOCARDIAL HYPERTROPHY IN FETAL SHEEP

To examine the cardiovascular effects on the fetus of an elevated umbi lical vascular resistance resulting in fetal hypoxemia, we embolized t he fetal side of the placenta in pregnant sheep and measured cardiovas cular and hormonal changes and cellular growth in fetal heart. Chronic ally catheterized fetal sheep were embolized (n = 6) for 21 days betwe en 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, fet uses 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 norepinephrin e throughout the study period (P < 0.05). On day 21 of embolization, f etuses 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 hypertroph y. We conclude that, during chronic placental damage leading to fetal hypoxemia with an increase in umbilical artery resistance index, fetus es developed arterial hypertension and asymmetrical growth restriction and that increases in afterload to the heart and plasma norepinephrin e likely caused fetal myocardial hypertrophy.