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Novel Approach to Elucidate Human Baroreflex Regulation at the Brainstem Level: Pharmacological Testing During fMRI.

Gerlach, D. and Manuel, J. and Hoff, A. and Kronsbein, H. and Hoffmann, F. and Heusser, K. and Ehmke, H. and Diedrich, A. and Jordan, J. and Tank, J. and Beissner, F. (2019) Novel Approach to Elucidate Human Baroreflex Regulation at the Brainstem Level: Pharmacological Testing During fMRI. Frontiers in Neuroscience, 13, p. 193. Frontiers Media S.A.. DOI: 10.3389/fnins.2019.00193 ISSN 1662-4548

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Official URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411827/pdf/fnins-13-00193.pdf

Abstract

Brainstem nuclei govern the arterial baroreflex, which is crucial for heart rate and blood pressure control. Yet, brainstem function is difficult to explore in living humans and is therefore mostly studied using animal models or postmortem human anatomy studies. We developed a methodology to identify brainstem nuclei involved in baroreflex cardiovascular control in humans by combining pharmacological baroreflex testing with functional magnetic resonance imaging. Materials and Methods: In 11 healthy men, we applied eight repeated intravenous phenylephrine bolus doses of 25 and 75 μg followed by a saline flush using a remote-controlled injector during multiband functional magnetic resonance imaging (fMRI) acquisition of the whole brain including the brainstem. Continuous finger arterial blood pressure, respiration, and electrocardiogram (ECG) were monitored. fMRI data were preprocessed with a brainstem-specific pipeline and analyzed with a general linear model (GLM) to identify brainstem nuclei involved in central integration of the baroreceptor input. Results: Phenylephrine elicited a pressor response followed by a baroreflex-mediated lengthening of the RR interval (25 μg: 197 ± 15 ms; 75 μg: 221 ± 33 ms). By combining fMRI responses during both phenylephrine doses, we identified significant signal changes in the nucleus tractus solitarii (t = 5.97), caudal ventrolateral medulla (t = 4.59), rostral ventrolateral medulla (t = 7.11), nucleus ambiguus (t = 5.6), nucleus raphe obscurus (t = 6.45), and several other brainstem nuclei [p < 0.0005 family-wise error (few)-corr.]. Conclusion: Pharmacological baroreflex testing during fMRI allows characterizing central baroreflex regulation at the level of the brainstem in humans. Baroreflex-mediated activation and deactivation patterns are consistent with previous investigations in animal models. The methodology has the potential to elucidate human physiology and mechanisms of autonomic cardiovascular disease.

Item URL in elib:https://elib.dlr.de/129683/
Document Type:Article
Title:Novel Approach to Elucidate Human Baroreflex Regulation at the Brainstem Level: Pharmacological Testing During fMRI.
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Gerlach, D.Institute of Aerospace Medicine, German Aerospace Center, Cologne, GermanyUNSPECIFIED
Manuel, J.Institute for Neuroradiology, Hannover Medical School, Hannover, GermanyUNSPECIFIED
Hoff, A.Institute of Aerospace Medicine, German Aerospace Center, Cologne, GermanyUNSPECIFIED
Kronsbein, H.Institute of Aerospace Medicine, German Aerospace Center, Cologne, GermanyUNSPECIFIED
Hoffmann, F.Institute of Aerospace Medicine, German Aerospace Center, Cologne, GermanyUNSPECIFIED
Heusser, K.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIED
Ehmke, H.Institute of Cellular and Integrative Physiology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyUNSPECIFIED
Diedrich, A.Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Service, Vanderbilt University, Nashville, TNUNSPECIFIED
Jordan, J.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIED
Tank, J.Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany.UNSPECIFIED
Beissner, F.Institute for Neuroradiology, Hannover Medical School, Hannover, GermanyUNSPECIFIED
Date:5 March 2019
Journal or Publication Title:Frontiers in Neuroscience
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:13
DOI :10.3389/fnins.2019.00193
Page Range:p. 193
Publisher:Frontiers Media S.A.
ISSN:1662-4548
Status:Published
Keywords:baroreflex; blood pressure; brainstem; cardiovascular; fMRI; nuclei; regulation
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Forschung unter Weltraumbedingungen
DLR - Research theme (Project):R - Vorhaben Systemphysiologie
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Leitungsbereich ME
Institute of Aerospace Medicine > Cardiovascular Medicine in Aerospace
Institute of Aerospace Medicine
Deposited By: Schrage, Larissa
Deposited On:23 Oct 2019 10:26
Last Modified:28 Sep 2020 09:57

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