Cholinergic and β-adrenergic control of cardiovascular reflex responses to brief repeated asphyxia in term-equivalent fetal sheep

Abstract

The role of cholinergic and β-adrenergic activity in mediating fetal cardiovascular recovery from brief repeated episodes of asphyxia consistent with established labor, remains unclear. In this study, we tested the effect of cholinergic and β-adrenergic blockade on the fetal chemoreflex and fetal heart rate (FHR) overshoot responses during brief repeated asphyxia at rates consistent with early or active labor. Chronically instrumented fetal sheep at 0.85 of gestation received either i.v. atropine sulfate (cholinergic blockade, n=8) or vehicle (n=7) followed by 3 x 1-minute umbilical cord occlusions repeated every 5 minutes (1:5; consistent with early labor), or i.v. propranolol hydrochloride (β-adrenergic blockade, n=6) or vehicle (n=6) followed by 3 x 2-minute occlusions repeated every 5 minutes (2:5; consistent with active labor). In vehicle-controls, 1:5 occlusions were associated with rapid and sustained FHR decelerations followed by rapid return of FHR to baseline values after release of the occlusion. Cholinergic blockade abolished FHR decelerations during occlusions and caused FHR overshoot after release of the occlusion (P<0.05 vs. control 1:5). In vehicle-controls, 2:5 occlusions caused rapid and sustained FHR decelerations followed by FHR overshoot after release of the occlusion. β-adrenergic blockade was associated with greater reduction in FHR during occlusions and attenuated FHR overshoot (P<0.05 vs. control 2:5). These data demonstrate that the FHR overshoot pattern after asphyxia is mediated by a combination of attenuated parasympathetic activity and increased β-adrenergic stimulation of the fetal heart.