Author | Martins, Yuri C. | |
Author | Clemmer, Leah | |
Author | Orjuela-Sanchez, Pamela | |
Author | Zanini, Graziela M. | |
Author | Ong, Peng Kai | |
Author | Frangos, John A. | |
Author | Carvalho, Leonardo J. M. | |
Access date | 2016-02-02T15:46:53Z | |
Available date | 2016-02-02T15:46:53Z | |
Document date | 2013 | |
Citation | 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. | pt_BR |
ISSN | 1475-2875 | |
URI | https://www.arca.fiocruz.br/handle/icict/12684 | |
Language | eng | pt_BR |
Publisher | BioMed Central | pt_BR |
Rights | open access | pt_BR |
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 | pt_BR |
Type | Article | pt_BR |
DOI | 10.1186/1475-2875-12-138 | |
Abstract | 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. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA. | pt_BR |
Affilliation | La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA. | pt_BR |
Affilliation | 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. | pt_BR |
Affilliation | La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA. | pt_BR |
Affilliation | La Jolla Bioengineering Institute. Center for Malaria Research. San Diego, CA, USA. | pt_BR |
Affilliation | 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. | pt_BR |
Subject | ECG | pt_BR |
Subject | Adjunctive therapy | pt_BR |
Subject | Experimental cerebral malaria | pt_BR |
Subject | Nimodipine | pt_BR |
Subject | Blood pressure | pt_BR |
DeCS | Eletrocardiografia | pt_BR |
DeCS | Nimodipino | pt_BR |
DeCS | Pressão Sanguínea | pt_BR |
DeCS | Malária Cerebral | pt_BR |