Oral Presentation 46th Annual Meeting of the Fetal and Neonatal Physiological Society 2019

The sympathetic nervous system helps regulate cerebral perfusion during post-asphyxial seizures in preterm fetal sheep (#34)

Simerdeep K. Dhillon 1 , Mette Pederson 2 , Eleanor R. Gunn 1 , Christopher A. Lear 1 , Joanne O. Davidson 1 , Alistair J. Gunn 1 , Laura Bennet 1
  1. The University of Auckland, Auckland, New Zealand
  2. Aarhus University Hospital, Aarhus, Denmark

Introduction: Seizures in preterm born infants are associated with adverse neurodevelopmental outcomes, but little is known about the regulation of cerebral perfusion during seizures. The sympathetic nervous system (SNS) is the key regulator of cerebral perfusion recovery from asphyxia, thus this study examined the effects of SNS blockade on carotid blood flow (CaBF) during post-asphyxia seizures.

Methods: Preterm (0.7 gestation) fetal sheep received sham asphyxia (n = 8) or asphyxia induced by complete umbilical cord occlusion for 25 minutes. Fetuses then received either continuous intravenous infusion of saline (n=10) or the alpha-adrenergic antagonist phentolamine (10 mg/ml bolus/10 mg/h infusion) (n=10) from 15 minutes to 8 hours post-asphyxia. Post-mortems were performed 72 hours post-asphyxia.

Results: The onset of seizures after occlusion, seizure count, burden, average amplitude and duration were similar between the asphyxia groups. In the asphyxia-saline group, seizures were associated with an increase in mean arterial pressure (MAP), but reduced CaBF, that was associated with increased carotid vascular resistance (P<0.05). By contrast, phentolamine treatment was associated with no change in MAP, but a significant increase in CaBF with reduced carotid vascular resistance (P<0.05). The effect of phentolamine on CaBF during seizures lasted until 21 hours post-asphyxia; thereafter CaBF fell during seizures. Asphyxia-phentolamine was associated with greater hippocampal neuronal loss than asphyxia-saline (P<0.05), and 50% of phentolamine-treated fetuses developed focal infarcts in the hippocampus and striatum.

Conclusion: This study shows that CaBF during post-asphyxial seizures is regulated by the SNS. The preterm brain has exceptional anaerobic tolerance, and alpha (2)-adrenergic activity is an important inhibitory neuromodulator system as shown by increased hippocampal damage in the present study. We propose that SNS activity may help limit both blood flow and metabolic demand during short seizures. Moreover, inhibiting cerebral vasodilatation may help protect immature blood vessels from rapid, potentially injurious changes in perfusion.