2026-04-17T03:52:21Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/67422024-12-13T09:07:46Zcom_2072_378071com_2072_378040col_2072_378097

2023-11-08T15:27:14Z urn:hdl:11351/6742 Citric Acid Cycle Metabolites Predict Infarct Size in Pigs Submitted to Transient Coronary Artery Occlusion and Treated with Succinate Dehydrogenase Inhibitors or Remote Ischemic Perconditioning Consegal Perez, Marta Núñez, Norberto Barba Vert, Ignasi Benito Villabriga, Begoña Inserte Igual, Javier Ferreira González, Ignacio Rodríguez Sinovas, Antonio Ruiz Meana, Marisol Infart de miocardi Àcid cítric - Metabolisme Inhibidors enzimàtics DISEASES::Cardiovascular Diseases::Heart Diseases::Myocardial Ischemia::Myocardial Infarction PHENOMENA AND PROCESSES::Metabolism::Energy Metabolism::Metabolism::Citric Acid Cycle CHEMICALS AND DRUGS::Macromolecular Substances::Multiprotein Complexes::Multienzyme Complexes::Succinate Cytochrome c Oxidoreductase::Electron Transport Complex II::Succinate Dehydrogenase Other subheadings::Other subheadings::Other subheadings::/administration & dosage ENFERMEDADES::enfermedades cardiovasculares::enfermedades cardíacas::isquemia miocárdica::infarto de miocardio FENÓMENOS Y PROCESOS::metabolismo::metabolismo energético::metabolismo::ciclo del ácido cítrico COMPUESTOS QUÍMICOS Y DROGAS::sustancias macromoleculares::complejos multiproteicos::complejos multienzimáticos::succinato citocromo c oxidorreductasa::complejo II de transporte de electrones::succinato deshidrogenasa Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación Isquèmia-reperfusió; Infart de miocardi; Succinat deshidrogenasa Isquemia-reperfusión; Infarto de miocardio; Succinato deshidrogenasa Ischemia-reperfusion; Myocardial infarction; Succinate dehydrogenase Succinate dehydrogenase (SDH) inhibition with malonate during reperfusion reduced myocardial infarction in animals, whereas its endogenous substrate, succinate, is detected in plasma from STEMI patients. We investigated whether protection by SDH inhibition is additive to that of remote ischemic perconditioning (RIC) in pigs submitted to transient coronary artery occlusion, and whether protective maneuvers influence plasma levels of citric acid cycle metabolites. Forty pigs were submitted to 40 min coronary occlusion and reperfusion, and allocated to four groups (controls, sodium malonate 10 mmol/L, RIC, and malonate + RIC). Plasma was obtained from femoral and great cardiac veins and analyzed by LC-MS/MS. Malonate, RIC, and malonate + RIC reduced infarct size (24.67 ± 5.98, 25.29 ± 3.92 and 29.83 ± 4.62% vs. 46.47 ± 4.49% in controls, p < 0.05), but no additive effects were detected. Enhanced concentrations of succinate, fumarate, malate and citrate were observed in controls during initial reperfusion in the great cardiac vein, and most were reduced by cardioprotective maneuvers. Concentrations of succinate, fumarate, and malate significantly correlated with infarct size. In conclusion, despite the combination of SDH inhibition during reperfusion and RIC did not result in additive protection, plasma concentrations of selected citric acid cycle metabolites are attenuated by protective maneuvers, correlate with irreversible injury, and might become a prognosis tool in STEMI patients. This research was funded by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (grants PI17/01397 and CIBERCV) and the Spanish Society of Cardiology (Proyectos de la FEC para Investigación Básica en Cardiología 2018, Sociedad Española de Cardiología), and was cofinanced by the European Regional Development Fund (ERDF-FEDER, a way to build Europe). Antonio Rodríguez-Sinovas has a consolidated Miguel Servet contract. 2023-11-08T15:27:14Z 2023-11-08T15:27:14Z 2021-12-28T07:42:35Z 2021-12-28T07:42:35Z 2021-04-16 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/6742 International Journal of Molecular Sciences;22(8) https://doi.org/10.3390/ijms22084151 info:eu-repo/grantAgreement/ES/PE2013-2016/PI17%2F01397 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess MDPI Scientia