Selective Inhibition of Succinate Dehydrogenase in Reperfused Myocardium with Intracoronary Malonate Reduces Infarct Size
Valls-Lacalle, Laura (Hospital Universitari Vall d'Hebron)
Barba, Ignasi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Miró-Casas, Elisabet (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ruiz Meana, Marisol (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodríguez-Sinovas, Antonio (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García-Dorado, David (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Inhibition of succinate dehydrogenase (SDH) with malonate during reperfusion reduces infarct size in isolated mice hearts submitted to global ischemia. However, malonate has toxic effects that preclude its systemic administration in animals. Here we investigated the effect of intracoronary malonate on infarct size in pigs submitted to transient coronary occlusion. Under baseline conditions, 50 mmol/L of intracoronary disodium malonate, but not lower concentrations, transiently reduced systolic segment shortening in the region perfused by the left anterior descending coronary artery (LAD) in open-chest pigs. To assess the effects of SDH inhibition on reperfusion injury, saline or malonate 10 mmol/L were selectively infused into the area at risk in 38 animals submitted to ischemia-reperfusion. Malonate improved systolic shortening in the area at risk two hours after 15 min of ischemia (0. 18 ± 0. 07 vs 0. 00 ± 0. 01 a. u. , p = 0. 025, n = 3). In animals submitted to 40 min of ischemia, malonate reduced reactive oxygen species production (MitoSOX staining) during initial reperfusion and limited infarct size (36. 46 ± 5. 35 vs 59. 62 ± 4. 00%, p = 0. 002, n = 11), without modifying reperfusion arrhythmias. In conclusion, inhibition of SDH with intracoronary malonate during early reperfusion limits reperfusion injury and infarct size in pigs submitted to transient coronary occlusion without modifying reperfusion arrhythmias or contractile function in distant myocardium.
Grants:	Ministerio de Economía y Competitividad PI14/01431 Instituto de Salud Carlos III PI17/01397 Ministerio de Economía y Competitividad RD12/0042/0021
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Scientific reports, Vol. 8 (february 2018) , ISSN 2045-2322

DOI: 10.1038/s41598-018-20866-4
PMID: 29402957

10 p, 1.7 MB

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