TY - JOUR
T1 - Cholinergic and β-adrenergic control of cardiovascular reflex responses to brief repeated asphyxia in term-equivalent fetal sheep
AU - Galinsky, Robert
AU - Lear, Christopher A.
AU - Yamaguchi, Kyohei
AU - Wassink, Guido
AU - Westgate, Jennifer A.
AU - Bennet, Laura
AU - Gunn, Alistair J.
PY - 2016/11/10
Y1 - 2016/11/10
N2 - 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 intravenous atropine sulfate (cholinergic blockade; n = 7) or vehicle (n = 8) followed by 3 × 1-min umbilical cord occlusions repeated every 5 min (1:5; consistent with early labor), or intravenous propranolol hydrochloride (β-adrenergic blockade; n = 8) or vehicle (n = 6) followed by 3 × 2-min occlusions repeated every 5 min (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.
AB - 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 intravenous atropine sulfate (cholinergic blockade; n = 7) or vehicle (n = 8) followed by 3 × 1-min umbilical cord occlusions repeated every 5 min (1:5; consistent with early labor), or intravenous propranolol hydrochloride (β-adrenergic blockade; n = 8) or vehicle (n = 6) followed by 3 × 2-min occlusions repeated every 5 min (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.
KW - Autonomic nervous system
KW - Chemoreflex
KW - Fetal asphyxia
UR - http://www.scopus.com/inward/record.url?scp=84995400092&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00340.2016
DO - 10.1152/ajpregu.00340.2016
M3 - Article
AN - SCOPUS:84995400092
VL - 311
SP - R949-R956
JO - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
JF - American Journal of Physiology - Regulatory Integrative and Comparative Physiology
SN - 0363-6119
IS - 5
ER -