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

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...

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Autores principales: Schiffner, René, Bischoff, Sabine Juliane, Lehmann, Thomas, Rakers, Florian, Rupprecht, Sven, Reiche, Juliane, Matziolis, Georg, Schubert, Harald, Schwab, Matthias, Huber, Otmar, Schmidt, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454943/
https://www.ncbi.nlm.nih.gov/pubmed/28492488
http://dx.doi.org/10.3390/ijms18051031
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author Schiffner, René
Bischoff, Sabine Juliane
Lehmann, Thomas
Rakers, Florian
Rupprecht, Sven
Reiche, Juliane
Matziolis, Georg
Schubert, Harald
Schwab, Matthias
Huber, Otmar
Schmidt, Martin
author_facet Schiffner, René
Bischoff, Sabine Juliane
Lehmann, Thomas
Rakers, Florian
Rupprecht, Sven
Reiche, Juliane
Matziolis, Georg
Schubert, Harald
Schwab, Matthias
Huber, Otmar
Schmidt, Martin
author_sort Schiffner, René
collection PubMed
description 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.
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spelling pubmed-54549432017-06-08 Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling Schiffner, René Bischoff, Sabine Juliane Lehmann, Thomas Rakers, Florian Rupprecht, Sven Reiche, Juliane Matziolis, Georg Schubert, Harald Schwab, Matthias Huber, Otmar Schmidt, Martin Int J Mol Sci Article 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. MDPI 2017-05-11 /pmc/articles/PMC5454943/ /pubmed/28492488 http://dx.doi.org/10.3390/ijms18051031 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schiffner, René
Bischoff, Sabine Juliane
Lehmann, Thomas
Rakers, Florian
Rupprecht, Sven
Reiche, Juliane
Matziolis, Georg
Schubert, Harald
Schwab, Matthias
Huber, Otmar
Schmidt, Martin
Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling
title Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling
title_full Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling
title_fullStr Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling
title_full_unstemmed Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling
title_short Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling
title_sort redistribution of cerebral blood flow during severe hypovolemia and reperfusion in a sheep model: critical role of α1-adrenergic signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454943/
https://www.ncbi.nlm.nih.gov/pubmed/28492488
http://dx.doi.org/10.3390/ijms18051031
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