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

International Journal of Molecular Sciences

Georg Matziolis¹  Sven Rupprecht¹  Martin Schmidt²  Florian Rakers²  Juliane Reiche²  Harald Schubert³  Otmar Huber⁴  Sabine Juliane Bischoff⁴  Thomas Lehmann⁵  Matthias Schwab⁶  René Schiffner⁶ 

[1] Jena University Hospital-Friedrich Schiller University, 07743 Jena, Germany;Department of Neurology;Institute for Biochemistry II, Jena University Hospital-Friedrich Schiller University, 07743 Jena, Germany;Institute for Laboratory Animal Sciences and Welfare, Jena University Hospital-Friedrich Schiller University, 07743 Jena, Germany;Institute of Medical Statistics, Computer Sciences and Documentation Science, Jena University Hospital-Friedrich Schiller University, 07743 Jena, Germany;Orthopedic Department, Campus Eisenberg, Jena University Hospital-Friedrich Schiller University, 07607 Eisenberg, Germany;

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

DOI  :  10.3390/ijms18051031

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown