Dataset Information

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

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.

SUBMITTER: Martins YC

PROVIDER: S-EPMC3642006 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Publications

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 YC Clemmer Leah L Orjuela-Sánchez Pamela P Zanini Graziela M GM Ong Peng Kai PK Frangos John A JA Carvalho Leonardo J M LJ

Malaria journal 20130424

<h4>Background</h4>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 effe ...[more]

PMID: 23617605

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Project description:ObjectiveContinuous blood pressure (BP) provides valuable information for the disease management of patients with arrhythmias. The traditional intra-arterial method is too invasive for routine healthcare settings, whereas cuff-based devices are inferior in reliability and comfortable for long-term BP monitoring during arrhythmias. The study aimed to investigate an indirect method for continuous and cuff-less BP estimation based on electrocardiogram (ECG) and photoplethysmogram (PPG) signals during arrhythmias and to test its reliability for the determination of BP using invasive BP (IBP) as reference.MethodsThirty-five clinically stable patients (15 with ventricular arrhythmias and 20 with supraventricular arrhythmias) who had undergone radiofrequency ablation were enrolled in this study. Their ECG, PPG, and femoral arterial IBP signals were simultaneously recorded with a multi-parameter monitoring system. Fifteen features that have the potential ability in indicating beat-to-beat BP changes during arrhythmias were extracted from the ECG and PPG signals. Four machine learning algorithms, decision tree regression (DTR), support vector machine regression (SVR), adaptive boosting regression (AdaboostR), and random forest regression (RFR), were then implemented to develop the BP models.ResultsThe results showed that the mean value ± standard deviation of root mean square error for the estimated systolic BP (SBP), diastolic BP (DBP) with the RFR model against the reference in all patients were 5.87 ± 3.13 and 3.52 ± 1.38 mmHg, respectively, which achieved the best performance among all the models. Furthermore, the mean error ± standard deviation of error between the estimated SBP and DBP with the RFR model against the reference in all patients were -0.04 ± 6.11 and 0.11 ± 3.62 mmHg, respectively, which complied with the Association for the Advancement of Medical Instrumentation and the British Hypertension Society (Grade A) standards.ConclusionThe results indicated that the utilization of ECG and PPG signals has the potential to enable cuff-less and continuous BP estimation in an indirect way for patients with arrhythmias.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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