Selective Inhibition of Succinate Dehydrogenase in Reperfused Myocardium with Intracoronary Malonate Reduces Infarct Size

Laura Valls-Lacalle, Ignasi Barba, Elisabet Miró-Casas, Marisol Ruiz-Meana, Antonio Rodríguez-Sinovas, David García-Dorado

Research output: Contribution to journalArticleResearch

30 Citations (Scopus)

Abstract

© 2018 The Author(s). 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.
Original languageEnglish
Article number2442
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 1 Dec 2018

Fingerprint

Dive into the research topics of 'Selective Inhibition of Succinate Dehydrogenase in Reperfused Myocardium with Intracoronary Malonate Reduces Infarct Size'. Together they form a unique fingerprint.

Cite this