Hyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heart
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 hyperpolariz...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2021
|
| _version_ | 1797066218096558080 |
|---|---|
| author | Savic, D Ball, V holster, L Hauton, D Timm, K Curtis, M Heather, L Tyler, D |
| author_facet | Savic, D Ball, V holster, L Hauton, D Timm, K Curtis, M Heather, L Tyler, D |
| author_sort | Savic, D |
| collection | OXFORD |
| description | 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.
|
| first_indexed | 2024-03-06T21:39:17Z |
| format | Journal article |
| id | oxford-uuid:475865b7-c9c0-4274-a35e-374b21cedd2e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:39:17Z |
| publishDate | 2021 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:475865b7-c9c0-4274-a35e-374b21cedd2e2022-03-26T15:19:52ZHyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heartJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:475865b7-c9c0-4274-a35e-374b21cedd2eEnglishSymplectic ElementsWiley2021Savic, DBall, Vholster, LHauton, DTimm, KCurtis, MHeather, LTyler, DThe 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. |
| spellingShingle | Savic, D Ball, V holster, L Hauton, D Timm, K Curtis, M Heather, L Tyler, D Hyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heart |
| title | Hyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heart |
| title_full | Hyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heart |
| title_fullStr | Hyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heart |
| title_full_unstemmed | Hyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heart |
| title_short | Hyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heart |
| title_sort | hyperpolarized magnetic resonance shows that the antiischemic drug meldonium leads to increased flux through pyruvate dehydrogenase in vivo resulting in improved postischemic function in the diabetic heart |
| work_keys_str_mv | AT savicd hyperpolarizedmagneticresonanceshowsthattheantiischemicdrugmeldoniumleadstoincreasedfluxthroughpyruvatedehydrogenaseinvivoresultinginimprovedpostischemicfunctioninthediabeticheart AT ballv hyperpolarizedmagneticresonanceshowsthattheantiischemicdrugmeldoniumleadstoincreasedfluxthroughpyruvatedehydrogenaseinvivoresultinginimprovedpostischemicfunctioninthediabeticheart AT holsterl hyperpolarizedmagneticresonanceshowsthattheantiischemicdrugmeldoniumleadstoincreasedfluxthroughpyruvatedehydrogenaseinvivoresultinginimprovedpostischemicfunctioninthediabeticheart AT hautond hyperpolarizedmagneticresonanceshowsthattheantiischemicdrugmeldoniumleadstoincreasedfluxthroughpyruvatedehydrogenaseinvivoresultinginimprovedpostischemicfunctioninthediabeticheart AT timmk hyperpolarizedmagneticresonanceshowsthattheantiischemicdrugmeldoniumleadstoincreasedfluxthroughpyruvatedehydrogenaseinvivoresultinginimprovedpostischemicfunctioninthediabeticheart AT curtism hyperpolarizedmagneticresonanceshowsthattheantiischemicdrugmeldoniumleadstoincreasedfluxthroughpyruvatedehydrogenaseinvivoresultinginimprovedpostischemicfunctioninthediabeticheart AT heatherl hyperpolarizedmagneticresonanceshowsthattheantiischemicdrugmeldoniumleadstoincreasedfluxthroughpyruvatedehydrogenaseinvivoresultinginimprovedpostischemicfunctioninthediabeticheart AT tylerd hyperpolarizedmagneticresonanceshowsthattheantiischemicdrugmeldoniumleadstoincreasedfluxthroughpyruvatedehydrogenaseinvivoresultinginimprovedpostischemicfunctioninthediabeticheart |