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, Marta (Universitat Autònoma de Barcelona. Departament de Medicina)
Núñez, Norberto (Universitat Autònoma de Barcelona. Departament de Medicina)
Barba, Ignasi (Universitat Autònoma de Barcelona. Departament de Medicina)
Benito, Begoña (Universitat Autònoma de Barcelona. Departament de Medicina)
Ruiz Meana, Marisol (Universitat Autònoma de Barcelona. Departament de Medicina)
Inserte, Javier (Universitat Autònoma de Barcelona. Departament de Medicina)
Ferreira-Gonzalez, Ignacio (Universitat Autònoma de Barcelona. Departament de Medicina)
Rodríguez-Sinovas, Antonio (Universitat Autònoma de Barcelona. Departament de Medicina)

Fecha:	2021
Resumen:	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.
Ayudas:	Instituto de Salud Carlos III PI17/01397
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Succinate dehydrogenase ; Malonate ; Remote ischemic conditioning ; Myocardial infarction ; Ischemia-reperfusion
Publicado en:	International journal of molecular sciences, Vol. 22 (april 2021) , ISSN 1422-0067

DOI: 10.3390/ijms22084151
PMID: 33923786

18 p, 4.8 MB

El registro aparece en las colecciones:
Artículos > Artículos de investigación
Artículos > Artículos publicados