scholarly journals 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

2021 ◽  
Author(s):  
Dragana Savic ◽  
Vicky Ball ◽  
Lorenz Holzner ◽  
David Hauton ◽  
Kerstin N. Timm ◽  
...  
2020 ◽  
Author(s):  
Dragana Savic ◽  
Vicky Ball ◽  
Lorenz Holzner ◽  
David Hauton ◽  
Kerstin Timm ◽  
...  

Abstract Background: 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. Methods: 36 male Wistar rats were injected with either placebo or streptozotocin (55mg/kg) to induce a model of type-1 diabetes. Daily treatment with either saline or Meldonium (100mg/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.Results: Meldonium had no significant effect on blood glucose levels 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, indicating an increase in cardiac glucose oxidation. Hyperpolarized magnetic resonance further demonstrated that Meldonium reduced acetylcarnitine by 2.1-fold in both diabetic and control animals. The increase in in vivo glucose oxidation was accompanied by an improvement in ex vivo post-ischemic function, where Meldonium elevated rate pressure product by 1.3-fold and 1.5-fold in the control and diabetic animals respectively. Conclusion: Meldonium improves in vivo glucose utilization in the diabetic heart, contributing to improved cardiac recovery post-ischemia.


2008 ◽  
Vol 105 (33) ◽  
pp. 12051-12056 ◽  
Author(s):  
M. A. Schroeder ◽  
L. E. Cochlin ◽  
L. C. Heather ◽  
K. Clarke ◽  
G. K. Radda ◽  
...  

Author(s):  
D.J. Meyerhoff

Magnetic Resonance Imaging (MRI) observes tissue water in the presence of a magnetic field gradient to study morphological changes such as tissue volume loss and signal hyperintensities in human disease. These changes are mostly non-specific and do not appear to be correlated with the range of severity of a certain disease. In contrast, Magnetic Resonance Spectroscopy (MRS), which measures many different chemicals and tissue metabolites in the millimolar concentration range in the absence of a magnetic field gradient, has been shown to reveal characteristic metabolite patterns which are often correlated with the severity of a disease. In-vivo MRS studies are performed on widely available MRI scanners without any “sample preparation” or invasive procedures and are therefore widely used in clinical research. Hydrogen (H) MRS and MR Spectroscopic Imaging (MRSI, conceptionally a combination of MRI and MRS) measure N-acetylaspartate (a putative marker of neurons), creatine-containing metabolites (involved in energy processes in the cell), choline-containing metabolites (involved in membrane metabolism and, possibly, inflammatory processes),


2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S692-S692
Author(s):  
Mathias Hoehn ◽  
Uwe Himmelreich ◽  
Ralph Weber ◽  
Pedro Ramos-Cabrer ◽  
Susanne Wegener ◽  
...  

2018 ◽  
Author(s):  
Danila Barskiy ◽  
Lucia Ke ◽  
Xingyang Li ◽  
Vincent Stevenson ◽  
Nevin Widarman ◽  
...  

<p>Hyperpolarization techniques based on the use of parahydrogen provide orders of magnitude signal enhancement for magnetic resonance spectroscopy and imaging. The main drawback limiting widespread applicability of parahydrogen-based techniques in biomedicine is the presence of organometallic compounds (the polarization transfer catalysts) in solution with hyperpolarized contrast agents. These catalysts are typically complexes of platinum-group metals and their administration in vivo should be avoided.</p> <p><br></p><p>Herein, we show how extraction of a hyperpolarized compound from an organic phase to an aqueous phase combined with a rapid (less than 10 seconds) Ir-based catalyst capture by metal scavenging agents can produce pure parahydrogen-based hyperpolarized contrast agents as demonstrated by high-resolution nuclear magnetic resonance (NMR) spectroscopy and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The presented methodology enables fast and efficient means of producing pure hyperpolarized aqueous solutions for biomedical and other uses.</p>


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