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Effect of Pulsatile Intravenous Oxytocin Administration to Pregnant Sheep Over the Last Third of Gestation on Fetal ACTH and Cortisol Responses to Hypotension

Drew Sadowsky, PhD

Susan Zarzeczny, BS

Laboratory for Pregnancy and Newborn Research, College of Veterinary Medicine, Cornell University, Ithaca, New York

Peter W. Nathanielsz, MD, PhD, ScD

Laboratory for Pregnancy and Newborn Research, College of Veterinary Medicine, Cornell University, Ithaca, New York; Laboratory for Pregnancy and Newborn Research, Department of Physiology, T9015 VRT, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401

Objective: To examine the effect of increasing myometrial contractility in the last third of gestation on ovine fetal response to hypotension.

Methods: Oxytocin (600 µ/U/kg/minute) or saline was infused via the maternal jugular vein as 5-minute pulses every 20 n inutes, starting at 97 ± 1 days of gestational age (mean ± standard error of the mean) until labor. Fetal hypotension (10 minutes) was induced by intravenous nitroprusside infusion at 133 ± 1 days' gestation.

Results: Ewes from both groups went into labor at the same gestational age. Total fetal body and adrenal gland weights were higher in controls than in the oxytocin-treated group. Maternal arterial pH and blood gas values were normal throughout the study. At 132-136 days' gestation, fetal arterial oxygen pressure was lower in the oxytocin group than in controls (P < .05). Basal fetal ACTH concentrations did not change between 130 and 136 days in both groups. The mean fetal plasma ACTH concentration was not different between the control (40.6 ± 4.1 pg/mL) and oxytocin groups (32.6 ± 4.9 pg/mL). Pre-hypotension fetal plasma ACTH was similar in both groups, whereas cortisol was lower in the oxytocin group. Hypotension significantly increased fetal plasma ACTH and cortisol concentrations; however, both ACTH and cortisol responses were smaller in the oxytocin group (P < .05).

Conclusions: Increased myometrial contractility throughout the last third of gestation modifies the normal ACTH and cortisol relation at the critical time of prepartum increase in adrenocortical activity. In addition, fetal ACTH and cortisol responses to hypotension are diminished in fetuses exposed to such a prolonged increase in myometrial contractility. These observations support the hypothesis that myometrial contractility influences fetal neuroendocrine development.

Key Words: Fetal hypotension • myometrium • contractures • ACTH • cortisol • oxytocin • sheep

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