Evidence mapPaperPMID 33458907Full record

ArticleNMR in biomedicine2021

Hyperpolarized magnetic resonance shows that the anti-ischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved post-ischemic function in the diabetic heart.

Dragana Savic, Vicky Ball, Lorenz Holzner, David Hauton, Kerstin N Timm, M Kate Curtis, Lisa C Heather, Damian J Tyler

Open access · hybridAbstract read
In one paragraph

Article in NMR in biomedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.1field-weighted citation impact, top 25% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Dragana SavicCardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.ORCID 0000-0002-2181-3196
Vicky BallCardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Lorenz HolznerDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
David HautonCardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Kerstin N TimmCardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
M Kate CurtisCardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Lisa C HeatherCardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
Damian J TylerCardiac Metabolism Research Group (CMRG), Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.ORCID 0000-0002-0780-8905
Oxford Research Group · GBUniversity of Cambridge · GB

Funding

British Heart Foundation FS/10/002/28078British Heart Foundation FS/14/17/30634British Heart Foundation FS/16/7/31843British Heart Foundation FS/17/58/33072British Heart Foundation FS/19/18/34252British Heart Foundation RE/13/1/30181Department of HealthMedical Research Council G0601490
6 · The paper itself

Abstract

The diabetic heart has a decreased ability to metabolize glucose. The anti-ischemic drug meldonium may provide a route to counteract this by reducing l-carnitine levels, resulting in improved cardiac glucose utilization. Therefore, the aim of this study was to use the novel technique of hyperpolarized magnetic resonance to investigate the in vivo effects of treatment with meldonium on cardiac metabolism and function in control and diabetic rats. Thirty-six male Wistar rats were injected either with vehicle, or with streptozotocin (55 mg/kg) to induce a model of type 1 diabetes. Daily treatment with either saline or meldonium (100 mg/kg/day) was undertaken for three weeks. in vivo cardiac function and metabolism were assessed with CINE MRI and hyperpolarized magnetic resonance respectively. Isolated perfused hearts were challenged with low-flow ischemia/reperfusion to assess the impact of meldonium on post-ischemic recovery. Meldonium had no significant effect on blood glucose concentrations or on baseline cardiac function. However, hyperpolarized magnetic resonance revealed that meldonium treatment elevated pyruvate dehydrogenase flux by 3.1-fold and 1.2-fold in diabetic and control animals, respectively, suggesting an increase in cardiac glucose oxidation. Hyperpolarized magnetic resonance further demonstrated that meldonium reduced the normalized acetylcarnitine signal by 2.1-fold in both diabetic and control animals. The increase in pyruvate dehydrogenase flux in vivo was accompanied by an improvement in post-ischemic function ex vivo, as meldonium elevated the rate pressure product by 1.3-fold and 1.5-fold in the control and diabetic animals, respectively. In conclusion, meldonium improves in vivo pyruvate dehydrogenase flux in the diabetic heart, contributing to improved cardiac recovery after ischemia.

Indexed as

AnimalsDiabetes Mellitus, ExperimentalGlucoseMagnetic Resonance SpectroscopyMaleMetabolomicsMethylhydrazinesMyocardial IschemiaMyocardiumPyruvate Dehydrogenase ComplexRatsRats, WistarStreptozocin3-(2,2,2-trimethylhydrazine)propionateGlucoseMethylhydrazinesPyruvate Dehydrogenase ComplexStreptozocincardiac functiondiabeteshyperpolarized MRIlangendorff perfusionmeldoniummetabolismpyruvate dehydrogenase fluxstreptozotocin

Identifiers

PMID33458907
PMCPMC8609426
OpenAlexW3122177151

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.