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The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat

BACKGROUND: Mefloquine is an anti-malarial drug that can have neurological side effects. This study examines how mefloquine (MF) influences central nervous control of autonomic and respiratory systems using the arterially perfused working heart brainstem preparation (WHBP) of the rat. Recordings of...

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Autores principales: Lall, Varinder K, Dutschmann, Mathias, Deuchars, Jim, Deuchars, Susan A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541349/
https://www.ncbi.nlm.nih.gov/pubmed/23241425
http://dx.doi.org/10.1186/1423-0127-19-103
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author Lall, Varinder K
Dutschmann, Mathias
Deuchars, Jim
Deuchars, Susan A
author_facet Lall, Varinder K
Dutschmann, Mathias
Deuchars, Jim
Deuchars, Susan A
author_sort Lall, Varinder K
collection PubMed
description BACKGROUND: Mefloquine is an anti-malarial drug that can have neurological side effects. This study examines how mefloquine (MF) influences central nervous control of autonomic and respiratory systems using the arterially perfused working heart brainstem preparation (WHBP) of the rat. Recordings of nerve activity were made from the thoracic sympathetic chain and phrenic nerve, while heart rate (HR) and perfusion pressure were also monitored in the arterially perfused, decerebrate, rat WHBP. MF was added to the perfusate at 1 μM to examine its effects on baseline parameters as well as baroreceptor and chemoreceptor reflexes. RESULTS: MF caused a significant, atropine resistant, bradycardia and increased phrenic nerve discharge frequency. Chemoreceptor mediated sympathoexcitation (elicited by addition of 0.1 ml of 0.03% sodium cyanide to the aortic cannula) was significantly attenuated by the application of MF to the perfusate. Furthermore MF significantly decreased rate of return to resting HR following chemoreceptor induced bradycardia. An increase in respiratory frequency and attenuated respiratory-related sympathetic nerve discharge during chemoreceptor stimulation was also elicited with MF compared to control. However, MF did not significantly alter baroreceptor reflex sensitivity. CONCLUSIONS: These studies indicate that in the WHBP, MF causes profound alterations in autonomic and respiratory control. The possibility that these effects may be mediated through actions on connexin 36 containing gap junctions in central neurones controlling sympathetic nervous outflow is discussed.
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spelling pubmed-35413492013-01-11 The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat Lall, Varinder K Dutschmann, Mathias Deuchars, Jim Deuchars, Susan A J Biomed Sci Research BACKGROUND: Mefloquine is an anti-malarial drug that can have neurological side effects. This study examines how mefloquine (MF) influences central nervous control of autonomic and respiratory systems using the arterially perfused working heart brainstem preparation (WHBP) of the rat. Recordings of nerve activity were made from the thoracic sympathetic chain and phrenic nerve, while heart rate (HR) and perfusion pressure were also monitored in the arterially perfused, decerebrate, rat WHBP. MF was added to the perfusate at 1 μM to examine its effects on baseline parameters as well as baroreceptor and chemoreceptor reflexes. RESULTS: MF caused a significant, atropine resistant, bradycardia and increased phrenic nerve discharge frequency. Chemoreceptor mediated sympathoexcitation (elicited by addition of 0.1 ml of 0.03% sodium cyanide to the aortic cannula) was significantly attenuated by the application of MF to the perfusate. Furthermore MF significantly decreased rate of return to resting HR following chemoreceptor induced bradycardia. An increase in respiratory frequency and attenuated respiratory-related sympathetic nerve discharge during chemoreceptor stimulation was also elicited with MF compared to control. However, MF did not significantly alter baroreceptor reflex sensitivity. CONCLUSIONS: These studies indicate that in the WHBP, MF causes profound alterations in autonomic and respiratory control. The possibility that these effects may be mediated through actions on connexin 36 containing gap junctions in central neurones controlling sympathetic nervous outflow is discussed. BioMed Central 2012-12-15 /pmc/articles/PMC3541349/ /pubmed/23241425 http://dx.doi.org/10.1186/1423-0127-19-103 Text en Copyright ©2012 Lall et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Lall, Varinder K
Dutschmann, Mathias
Deuchars, Jim
Deuchars, Susan A
The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat
title The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat
title_full The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat
title_fullStr The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat
title_full_unstemmed The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat
title_short The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat
title_sort anti-malarial drug mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3541349/
https://www.ncbi.nlm.nih.gov/pubmed/23241425
http://dx.doi.org/10.1186/1423-0127-19-103
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