Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling

Int J Mol Sci. 2017 May 11;18(5):1031. doi: 10.3390/ijms18051031.

Abstract

Background: Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage.

Methods: Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored. Urapidil was used for α1A-adrenergic receptor blockade in dosages, which did not modify the MABP-response to blood loss. Western blot and quantitative reverse transcription polymerase chain reactions were used to determine adrenergic receptor expression in brain arterioles.

Results: During hypovolemia subcortical CBF was maintained at 81 ± 6% of baseline, whereas cortical CBF decreased to 40 ± 4% (p < 0.001). Reperfusion led to peak CBFs of about 70% above baseline in both brain regions. α1A-Adrenergic blockade massively reduced subcortical CBF during hemorrhage and reperfusion, and prevented hyperperfusion during reperfusion in the cortex. α1A-mRNA expression was significantly higher in the cortex, whereas α1D-mRNA expression was higher in the subcortex (p < 0.001).

Conclusions: α1-Adrenergic receptors are critical for perfusion redistribution: activity of the α1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the α1D-receptor subtype may determine the magnitude of redistribution responses.

Keywords: adrenergic regulation; alpha-adrenergic; cerebral blood flow; cerebral hemodynamics; cerebrovasvular disease; head trauma; neurodegenerative disease; resuscitation.

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists / pharmacology
  • Analysis of Variance
  • Animals
  • Arterial Pressure
  • Arterioles / chemistry
  • Arterioles / metabolism
  • Blood Gas Analysis
  • Cerebral Cortex / blood supply*
  • Cerebrovascular Circulation*
  • Disease Models, Animal
  • Female
  • Heart Rate
  • Hemorrhage / physiopathology
  • Hypovolemia / physiopathology*
  • Piperazines / pharmacology
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Renal Circulation
  • Reperfusion
  • Sheep
  • Shock / physiopathology*

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Piperazines
  • Receptors, Adrenergic, alpha-1
  • urapidil