The cerebral haemodynamic response to somatosensory stimulation in preterm newborn lambs is reduced with dopamine or dobutamine infusion

Exp Neurol. 2021 Jul:341:113687. doi: 10.1016/j.expneurol.2021.113687. Epub 2021 Mar 10.

Abstract

Background: In the adult brain, increases in neural activity lead to increases in local blood flow. However, in the preterm neonate, studies of cerebral functional haemodynamics have yielded inconsistent results, including negative responses suggesting decreased perfusion and localised tissue hypoxia, probably due to immature neurovascular coupling. Furthermore, the impact of vasoactive medications, such as dopamine and dobutamine used as inotropic therapies in preterm neonates, on cerebrovascular responses to somatosensory input is unknown. We aimed to characterise the cerebral haemodynamic functional response after somatosensory stimulation in the preterm newborn brain, with and without dopamine or dobutamine treatment.

Methods: We studied the cerebral haemodynamic functional response in 13 anaesthetised preterm lambs, using near infrared spectroscopy to measure changes in cerebral oxy- and deoxyhaemoglobin (ΔoxyHb, ΔdeoxyHb) following left median nerve stimulation using stimulus trains of 1.8, 4.8 and 7.8 s. The 4.8 and 7.8 s stimulations were repeated during dopamine or dobutamine infusion.

Results: Stimulation always produced a somatosensory evoked response. Majority of preterm lambs demonstrated positive functional responses (i.e. increased ΔoxyHb) in the contralateral cortex following stimulus trains of all durations. Dopamine increased baseline oxyHb and total Hb, whereas dobutamine increased baseline deoxyHb. Both dopamine and dobutamine reduced the evoked ΔoxyHb responses to 4.8 and 7.8 s stimulations.

Conclusions: Somatosensory stimulation increases cerebral oxygenation in the preterm brain, consistent with increased cerebral blood flow due to neurovascular coupling. Notably, our results show that dopamine/dobutamine reduces oxygen delivery relative to consumption in the preterm brain during somatosensory stimulations, suggesting there may be a risk of intermittent localised tissue hypoxia which has clear implications for clinical practice and warrants further investigation.

Keywords: Cerebral haemodynamic response; Dobutamine; Dopamine; Neurovascular coupling; Preterm brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cardiotonic Agents / administration & dosage
  • Cerebrovascular Circulation / drug effects*
  • Cerebrovascular Circulation / physiology
  • Dobutamine / administration & dosage*
  • Dopamine / administration & dosage*
  • Evoked Potentials, Somatosensory / drug effects*
  • Evoked Potentials, Somatosensory / physiology
  • Female
  • Hemodynamics / drug effects*
  • Hemodynamics / physiology
  • Infusions, Intravenous
  • Male
  • Pregnancy
  • Sheep
  • Somatosensory Cortex / drug effects*
  • Somatosensory Cortex / physiology
  • Spectroscopy, Near-Infrared / methods

Substances

  • Cardiotonic Agents
  • Dobutamine
  • Dopamine