Umbilical cord occlusion (UCO) is a hypoxic insult that has been used to model birth asphyxia and umbilical cord compression in utero. UCO triggers vigorous neural and endocrine responses that include increased plasma ACTH and cortisol concentrations, increased blood pressure (BP), and decreased heart rate (HR). We have previously reported that ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, can modify the fetal hemodynamic and ACTH responses to ventilatory hypoxia and cerebral ischemia-reperfusion. We performed the present experiments to test the hypothesis that ketamine has similar effects on the neuroendocrine and cardiovascular responses to UCO Fetal sheep were chronically catheterized at gestational day 125. Ketamine (3 mg/kg) was administered intravenously to the fetus 10 min prior to the insult. UCO was induced for 30 min by reducing the umbilical vein blood flow until fetal PaO2 levels were reduced from 17 ± 1 to 11 ± 1 mm Hg. UCO produced an initial increase on fetal BP in both control and ketamine groups (P = 0.018 time), followed by a decrease in the control group, but values remained higher with ketamine. HR decreased after UCO (P = 0.041 stimulus*time) in both groups, but the reduction was greater initially in control compared to ketamine groups. Fetal PaCO2 levels increased after UCO (P < 0.01 stimulus*time), but values were higher in the control versus ketamine groups. UCO significantly decreased fetal pH values (P < 0.01 stimulus*time) with a greater effect on the control versus ketamine group. Ketamine delayed the cortisol responses to UCO (P < 0.001 stimulus*time), and UCO produced a robust increase in ACTH levels from 19 ± 2 to 280 ± 27 pg/mL (P < 0.001 stimulus*time), but there were no differences in ACTH levels between UCO groups. We conclude that ketamine augmented the cardiovascular response to UCO, but did not alter the ACTH response to UCO.
Keywords: Endocrine; fetal hypoxia; hemodynamics; umbilical cord occlusion.
© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.