Cardioprotective effect of succinate dehydrogenase inhibition in rat hearts and human myocardium with and without diabetes mellitus

Ischemia reperfusion (IR) injury may be attenuated through succinate dehydrogenase (SDH) inhibition by dimethyl malonate (DiMAL). Whether SDH inhibition yields protection in diabetic individuals and translates into human cardiac tissue remain unknown. In isolated perfused hearts from 24 weeks old ma...

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Bibliographic Details
Published in:Scientific reports 2020-06, Vol.10 (1), p.10344-10344, Article 10344
Main Authors: Jespersen, Nichlas Riise, Hjortbak, Marie Vognstoft, Lassen, Thomas Ravn, Støttrup, Nicolaj Brejnholt, Johnsen, Jacob, Tonnesen, Pernille Tilma, Larsen, Steen, Kimose, Hans-Henrik, Bøtker, Hans Erik
Format: Article
Language:English
Subjects:
692/4017
692/4019/592
Aged
Animals
Cardiotonic Agents - pharmacology
Cardiotonic Agents - therapeutic use
Dehydrogenase
Dehydrogenases
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - complications
Female
Heart
Heart - diagnostic imaging
Heart - drug effects
Humanities and Social Sciences
Humans
Ischemia
Ischemic Preconditioning, Myocardial - methods
Isolated Heart Preparation
Male
Malonates - pharmacology
Malonates - therapeutic use
Middle Aged
Mitochondria
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondria - pathology
multidisciplinary
Muscle contraction
Myocardial Contraction - drug effects
Myocardial Infarction - complications
Myocardial Infarction - diagnosis
Myocardial Infarction - therapy
Myocardial Reperfusion Injury - diagnosis
Myocardial Reperfusion Injury - etiology
Myocardial Reperfusion Injury - prevention & control
Myocardium
Myocardium - cytology
Myocardium - pathology
Rats
Rats, Zucker
Reperfusion
Respiration
Rodents
Science
Science (multidisciplinary)
Succinate dehydrogenase
Succinate Dehydrogenase - antagonists & inhibitors
Succinate Dehydrogenase - metabolism
Treatment Outcome
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Summary:Ischemia reperfusion (IR) injury may be attenuated through succinate dehydrogenase (SDH) inhibition by dimethyl malonate (DiMAL). Whether SDH inhibition yields protection in diabetic individuals and translates into human cardiac tissue remain unknown. In isolated perfused hearts from 24 weeks old male Zucker diabetic fatty (ZDF) and age matched non-diabetic control rats and atrial trabeculae from patients with and without diabetes, we compared infarct size, contractile force recovery and mitochondrial function. The cardioprotective effect of a 10 minutes DiMAL administration prior to global ischemia and ischemic preconditioning (IPC) was evaluated. In non-diabetic hearts exposed to IR, DiMAL 0.1 mM reduced infarct size compared to IR (55 ± 7% vs. 69 ± 6%, p 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-67247-4