Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria

Detalhes bibliográficos
Autor(a) principal: Martins, Yuri C.
Data de Publicação: 2013
Outros Autores: Clemmer, Leah, Orjuela-Sanchez, Pamela, Zanini, Graziela M., Ong, Peng Kai, Frangos, John A., Carvalho, Leonardo J. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/12684
Resumo: La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Professor Paulo de Góes. Laboratório de Inflamação e Imunologia. Rio de Janeiro, RJ, Brasil.
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spelling Martins, Yuri C.Clemmer, LeahOrjuela-Sanchez, PamelaZanini, Graziela M.Ong, Peng KaiFrangos, John A.Carvalho, Leonardo J. M.2016-02-02T15:46:53Z2016-02-02T15:46:53Z2013MARTINS, Yuri C. et al. Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria. Malaria Journal, n. 12, p. 1-11, 2013.1475-2875https://www.arca.fiocruz.br/handle/icict/1268410.1186/1475-2875-12-138engBioMed CentralSlow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malariainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLa Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Professor Paulo de Góes. Laboratório de Inflamação e Imunologia. Rio de Janeiro, RJ, Brasil.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA /Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Serviço de Parasitologia. Rio de Janeiro, RJ, Brasil.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA.La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.Background: Human cerebral malaria (HCM) is a life-threatening complication caused by Plasmodium falciparum infection that continues to be a major global health problem despite optimal anti-malarial treatment. In the experimental model of cerebral malaria (ECM) by Plasmodium berghei ANKA, bolus administration of nimodipine at high doses together with artemether, increases survival of mice with ECM. However, the dose and administration route used is associated with cardiovascular side effects such as hypotension and bradycardia in humans and mice, which could preclude its potential use as adjunctive treatment in HCM. Methods: In the present study, alternative delivery systems for nimodipine during late-stage ECM in association with artesunate were searched to define optimal protocols to achieve maximum efficacy in increasing survival in rescue therapy while causing the least cardiac side effects. The baseline electrocardiogram (ECG) and arterial pressure characteristics of uninfected control animals and of mice with ECM and its response upon rescue treatment with artesunate associated or not with nimodipine is also analysed. Results: Nimodipine, given at 0.5 mg/kg/day via a slow and continuous delivery system by osmotic pumps, increases survival of mice with ECM when used as adjunctive treatment to artesunate. Mice with ECM showed hypotension and ECG changes, including bradycardia and increases in PR, QRS, QTc and ST interval duration. ECM mice also show increased QTc dispersion, heart rate variability (HRV), RMSSD, low frequency (LF) and high frequency (HF) bands of the power spectrum. Both sympathetic and parasympathetic inputs to the heart were increased, but there was a predominance of sympathetic tone as demonstrated by an increased LF/HF ratio. Nimodipine potentiated bradycardia when given by bolus injection, but not when via osmotic pumps. In addition, nimodipine shortened PR duration and improved HRV, RMSSD, LF and HF powers in mice with ECM. In addition, nimodipine did not increased hypotension or decreased the speed of arterial pressure recovery when used in rescue therapy with artesunate. Conclusions: These data show that slow and continuous delivery of lower doses of nimodipine improves survival of mice with ECM in rescue therapy with artesunate while showing a safer profile in terms of cardiovascular effects.ECGAdjunctive therapyExperimental cerebral malariaNimodipineBlood pressureEletrocardiografiaNimodipinoPressão SanguíneaMalária Cerebralinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/12684/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALleonardo2_carvalho_etal_IOC_2013.pdfleonardo2_carvalho_etal_IOC_2013.pdfapplication/pdf1312016https://www.arca.fiocruz.br/bitstream/icict/12684/2/leonardo2_carvalho_etal_IOC_2013.pdf1d0000f743d99eba7d206bada2bc59e5MD52TEXTleonardo2_carvalho_etal_IOC_2013.pdf.txtleonardo2_carvalho_etal_IOC_2013.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria
title Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria
spellingShingle Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria
Martins, Yuri C.
ECG
Adjunctive therapy
Experimental cerebral malaria
Nimodipine
Blood pressure
Eletrocardiografia
Nimodipino
Pressão Sanguínea
Malária Cerebral
title_short Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria
title_full Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria
title_fullStr Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria
title_full_unstemmed Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria
title_sort Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria
author Martins, Yuri C.
author_facet Martins, Yuri C.
Clemmer, Leah
Orjuela-Sanchez, Pamela
Zanini, Graziela M.
Ong, Peng Kai
Frangos, John A.
Carvalho, Leonardo J. M.
author_role author
author2 Clemmer, Leah
Orjuela-Sanchez, Pamela
Zanini, Graziela M.
Ong, Peng Kai
Frangos, John A.
Carvalho, Leonardo J. M.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Martins, Yuri C.
Clemmer, Leah
Orjuela-Sanchez, Pamela
Zanini, Graziela M.
Ong, Peng Kai
Frangos, John A.
Carvalho, Leonardo J. M.
dc.subject.en.pt_BR.fl_str_mv ECG
Adjunctive therapy
Experimental cerebral malaria
Nimodipine
Blood pressure
topic ECG
Adjunctive therapy
Experimental cerebral malaria
Nimodipine
Blood pressure
Eletrocardiografia
Nimodipino
Pressão Sanguínea
Malária Cerebral
dc.subject.decs.pt_BR.fl_str_mv Eletrocardiografia
Nimodipino
Pressão Sanguínea
Malária Cerebral
description La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA / Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Professor Paulo de Góes. Laboratório de Inflamação e Imunologia. Rio de Janeiro, RJ, Brasil.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2016-02-02T15:46:53Z
dc.date.available.fl_str_mv 2016-02-02T15:46:53Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv MARTINS, Yuri C. et al. Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria. Malaria Journal, n. 12, p. 1-11, 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/12684
dc.identifier.issn.none.fl_str_mv 1475-2875
dc.identifier.doi.none.fl_str_mv 10.1186/1475-2875-12-138
identifier_str_mv MARTINS, Yuri C. et al. Slow and continuous delivery of a low dose of nimodipine improves survival and electrocardiogram parameters in rescue therapy of mice with experimental cerebral malaria. Malaria Journal, n. 12, p. 1-11, 2013.
1475-2875
10.1186/1475-2875-12-138
url https://www.arca.fiocruz.br/handle/icict/12684
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/12684/1/license.txt
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