Sympathetic mechanisms in cerebral blood flow alterations induced by spinal cord stimulation

J Neurosurg. 2003 Oct;99(4):754-61. doi: 10.3171/jns.2003.99.4.0754.

Abstract

Object: Cervical spinal cord stimulation (SCS) has been found to augment cerebral blood flow (CBF) in a number of animal models, although the mechanisms underlying the cerebrovascular effects of SCS are poorly described. In this study, the authors examined the role of sympathetic tone in CBF alterations induced by SCS in rats.

Methods: Spinal cord stimulation was performed at three intervals while CBF was monitored with laser Doppler flowmetry (LDF). Either hexamethonium (5, 10, or 20 mg/kg), prazosin (0.25, 0.5, or 1 mg/kg), idazoxan (0.5, 1, or 2 mg/kg), propranolol (1, 2, or 4 mg/kg), or vehicle was administered intravenously before the second stimulation. Changes in LDF values due to SCS were recorded as the percentage of change from baseline values and were analyzed. In vehicle-treated animals, SCS increased LDF values by 60.5 +/- 1.8% over baseline, whereas both high-dose hexamethonium and prazosin completely abolished the SCS-induced increases in LDF values. On the other hand, LDF values increased by 50.9 +/- 4% and 61.4 +/- 4% after SCS in the presence of idazoxan or propranolol, respectively. Administration of sympathetic nervous system blockers resulted in a variable degree of systemic hypotension as well. Nevertheless, induced hypotension without sympathetic blockade had only a minimal effect on SCS-induced augmentation of LDF values (48 +/- 1.4% over baseline).

Conclusions: Sympathetic tone plays a major role in SCS-induced increases in CBF. This effect seems to be mediated primarily by alpha1-adrenergic receptors. Systemic hypotension alone cannot explain the effects of sympathetic blockade on the SCS response. Clinical use of SCS in the treatment of cerebral ischemia should take alpha1-adrenergic receptor sympathetic tone into account.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Antagonists / administration & dosage
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Brain / blood supply
  • Cerebrovascular Circulation / physiology
  • Electric Stimulation / instrumentation
  • Ganglionic Blockers / administration & dosage
  • Ganglionic Blockers / pharmacology
  • Hemodynamics / physiology
  • Hexamethonium / administration & dosage
  • Hexamethonium / pharmacology
  • Idazoxan / administration & dosage
  • Idazoxan / pharmacology
  • Injections, Intravenous
  • Laser-Doppler Flowmetry
  • Male
  • Prazosin / administration & dosage
  • Prazosin / pharmacology
  • Propranolol / administration & dosage
  • Propranolol / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, beta-1 / drug effects
  • Spinal Cord / blood supply*
  • Sympathetic Nervous System / blood supply
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology*

Substances

  • Adrenergic alpha-Antagonists
  • Ganglionic Blockers
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, beta-1
  • Hexamethonium
  • Propranolol
  • Prazosin
  • Idazoxan