Sustained sympathetic nervous system support of arterial blood pressure during repeated brief umbilical cord occlusions in near-term fetal sheep

Abstract

Sympathetic nervous system (SNS)-mediated peripheral vasoconstriction plays a key role in initial maintenance of blood pressure during rapid-onset asphyxia in the mammalian fetus, but it is attenuated after the first few minutes. It is unclear whether the SNS response is sustained during the brief, but frequently repeated, episodes of asphyxia characteristic of labor. In the present study, 14 fetal sheep at 0.85 of gestation received either chemical sympathectomy with 6-hydroxydopamine (6-OHDA; n = 7) or sham injection (control; n = 7), followed 4-5 days later by repeated 2-min episodes of complete umbilical cord occlusion every 5 min for up to 4 h or until mean arterial blood pressure (MAP) fell to <20 mmHg for two successive occlusions. In controls, umbilical cord occlusions were associated with a rapid initial fall in fetal heart rate (FHR) and femoral blood flow (FBF), with initial hypertension, followed by progressive development of hypotension during ongoing occlusions. Sympathectomy was associated with attenuation of the initial rise in MAP during umbilical cord occlusion, and after the onset of hypotension, a markedly more rapid fall of MAP to the nadir, with a correspondingly slower fall in FBF (P < 0.05). In contrast, MAP and FHR between successive occlusions were higher after sympathectomy (P < 0.05). There was no significant difference in the number of occlusions before terminal hypotension (6-OHDA; 16.1 ± 2.2 vs. control; 18.7 ± 2.3). These data show that SNS activity provides ongoing support for fetal MAP during prolonged exposure to brief repeated asphyxia.

Sympathetic neural activation does not mediate heart rate variability during repeated brief umbilical cord occlusions in near‐term fetal sheep

“…Fetal blood gases, cortisol, catecholamine and cardiovascular responses during the occlusion series have previously been reported (Galinsky et al . ). Briefly, repeated occlusions were associated with progressive development of severe mixed respiratory and metabolic acidosis that was no different between groups (data not shown).…”

“…; Galinsky et al . ). This finding suggests that myocardial SNS activity is attenuated during the immediate recovery from episodes of brief but intense asphyxia and illustrates that assumptions derived from studies in healthy, normoxic fetuses are not always valid during major stressors such as asphyxia.…”

“…), and we have recently demonstrated that sympathectomy impaired fetal reflex adaptation during repeated exposure to episodes of brief asphyxia, resulting in impaired blood pressure support, although overall fetal survival was not impaired (Galinsky et al . ). Clinically, there is indirect evidence from changes in the specific frequency bands of FHRV during labour that developing fetal acidosis is associated with impairment of SNS activity that may be reflected in changes in FHRV (Siira et al .…”

“…Confirming a key role for non‐neural control of the adrenal response, we have shown in the present cohort that the considerable increase in circulating catecholamine levels during repeated brief umbilical cord occlusions was unchanged by sympathectomy (Galinsky et al . ). Thus, in the present study we specifically investigated the contribution of the SNS to FHRV.…”

“…To test our hypothesis we performed chemical sympathectomy with the neurotoxin 6‐hydroxydopamine (6‐OHDA) on healthy fetal sheep at 0.85 of gestation (Galinsky et al . ), followed by exposure to repeated brief umbilical cord occlusions at a frequency consistent with active labour (Westgate et al . ).…”