Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling
René Schiffner 1,2,*,†, Sabine Juliane Bischoff 3,†, Thomas Lehmann 4, Florian Rakers 2, Sven Rupprecht 2, Juliane Reiche 5, Georg Matziolis 1, Harald Schubert 3, Matthias Schwab 2, Otmar Huber 5
and Martin Schmidt 5
and Martin Schmidt 5
1
Orthopedic Department, Campus Eisenberg, Jena University Hospital-Friedrich Schiller University, 07607 Eisenberg, Germany
2
Department of Neurology; Jena University Hospital-Friedrich Schiller University, 07743 Jena, Germany
3
Institute for Laboratory Animal Sciences and Welfare, Jena University Hospital-Friedrich Schiller University, 07743 Jena, Germany
4
Institute of Medical Statistics, Computer Sciences and Documentation Science, Jena University Hospital-Friedrich Schiller University, 07743 Jena, Germany
5
Institute for Biochemistry II, Jena University Hospital-Friedrich Schiller University, 07743 Jena, Germany
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editor: Kuniaki Ogasawara
Int. J. Mol. Sci. 2017, 18(5), 1031; https://doi.org/10.3390/ijms18051031
Received: 22 March 2017 / Revised: 5 May 2017 / Accepted: 8 May 2017 / Published: 11 May 2017
(This article belongs to the Special Issue Cerebral Blood Flow and Metabolism)
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. View Full-TextKeywords:
adrenergic regulation; alpha-adrenergic; cerebral blood flow; cerebral hemodynamics; resuscitation; head trauma; cerebrovasvular disease; neurodegenerative disease
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Schiffner, R.; Bischoff, S.J.; Lehmann, T.; Rakers, F.; Rupprecht, S.; Reiche, J.; Matziolis, G.; Schubert, H.; Schwab, M.; Huber, O.; Schmidt, M. 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, 18, 1031.
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