Universität zu Köln

Gerlach, Darius A., Manuel, Jorge ORCID: 0000-0003-1983-1448, Hoff, Alex, Kronsbein, Hendrik, Hoffmann, Fabian, Heusser, Karsten, Ehmke, Heimo, Diedrich, Andre, Jordan, Jens, Tank, Jens and Beissner, Florian (2019). Novel Approach to Elucidate Human Baroreflex Regulation at the Brainstem Level: Pharmacological Testing During fMRI. Front. Neurosci., 13. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1662-453X

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Abstract

Introduction: 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 mu g 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 mu g: 197 +/- 15 ms; 75 mu g: 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 Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gerlach, Darius A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Manuel, Jorge UNSPECIFIED orcid.org/0000-0003-1983-1448 UNSPECIFIED Hoff, Alex UNSPECIFIED UNSPECIFIED UNSPECIFIED Kronsbein, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Heusser, Karsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Ehmke, Heimo UNSPECIFIED UNSPECIFIED UNSPECIFIED Diedrich, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Jordan, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Tank, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Beissner, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-154237
DOI:	10.3389/fnins.2019.00193
Journal or Publication Title:	Front. Neurosci.
Volume:	13
Date:	2019
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1662-453X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SYMPATHETIC-NERVE ACTIVITY; BLOOD-PRESSURE; ACTIVATION THERAPY; SENSITIVITY; REFLEX; SUSCEPTIBILITY; PHENYLEPHRINE; STIMULATION; VENTILATION; MECHANISMS Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15423