278b99cac1af62f8870af5e65d23b0d4 pmc_33923786.pdf d558f8c24127860e716f3d26c3a4c54a169238b4 pmc_33923786.pdf 211b7871d08aa8cca78999e24aa7bd7bfdc5f3c9b5374001cb0697a428f6f720 pmc_33923786.pdf Title: 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 Subject: 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. Keywords: succinate dehydrogenase; malonate; remote ischemic conditioning; myocardial infarction; ischemia-reperfusion Author: Marta Consegal, Norberto Núñez, Ignasi Barba, Begoña Benito, Marisol Ruiz-Meana, Javier Inserte, Ignacio Ferreira-González and Antonio Rodríguez-Sinovas Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sun Apr 18 12:46:23 2021 CEST ModDate: Sun Apr 18 12:48:54 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 5044051 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- DSXKDM+VnURWPalladioL Type 1 Custom yes yes no 10 0 KOJFQB+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 EXNPQZ+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 PWKZFL+URWPalladioL-BoldItal Type 1 Custom yes yes no 24 0 RYWKZX+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 YFFKLH+CMSY10 Type 1 Builtin yes yes no 32 0 JGBJTI+VnURWPalladioL-Bold Type 1 Custom yes yes no 36 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 44 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 47 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 69 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 73 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 77 0 QQOGDI+EURM10 Type 1 Builtin yes yes no 98 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:20:02 CEST RepresentationInformation: pmc_33923786.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:09:51 CEST Size: 5044051 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 404 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Ischemia-Reperfusion Injury Destination: subsection.2.1 Children: Item: Title: Hemodynamic Variables, LAD Coronary Blood Flow and Regional Myocardial Contractility Destination: subsubsection.2.1.1 Item: Title: Infarct Size Destination: subsubsection.2.1.2 Item: Title: Reperfusion Arrhythmias Destination: subsubsection.2.1.3 Item: Title: Targeted LC-MS/MS Analysis of Citric Acid Cycle Metabolites in Porcine Plasma Samples Destination: subsection.2.2 Item: Title: Discussion Destination: section.3 Children: Item: Title: Cardioprotection by SDH Inhibition and RIC Destination: subsection.3.1 Item: Title: Targeted Analysis of Citric Acid Cycle Metabolites by LC-MS/MS Destination: subsection.3.2 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Animals and Instrumentation Destination: subsection.4.1 Item: Title: Regional Myocardial Function Destination: subsection.4.2 Item: Title: Study Protocols Destination: subsection.4.3 Item: Title: Area at Risk and Infarct Size Destination: subsection.4.4 Item: Title: Reperfusion Arrhythmias Destination: subsection.4.5 Item: Title: Targeted LC-MS/MS Analysis of Citric Acid Cycle Metabolites in Porcine Plasma Samples Destination: subsection.4.6 Item: Title: Statistical Analysis Destination: subsection.4.7 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: 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 Author: Marta Consegal, Norberto Núñez, Ignasi Barba, Begoña Benito, Marisol Ruiz-Meana, Javier Inserte, Ignacio Ferreira-González and Antonio Rodríguez-Sinovas Subject: 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. Keywords: succinate dehydrogenase; malonate; remote ischemic conditioning; myocardial infarction; ischemia-reperfusion Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sun Apr 18 12:46:23 CEST 2021 ModDate: Sun Apr 18 12:48:54 CEST 2021 ID: 0x429d84d71232c70e923b943047ab6b4d, 0x429d84d71232c70e923b943047ab6b4d Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: YFFKLH+CMSY10 FontSubset: true FirstChar: 0 LastChar: 48 FontDescriptor: FontName: YFFKLH+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: QQOGDI+EURM10 FontSubset: true FirstChar: 22 LastChar: 28 FontDescriptor: FontName: QQOGDI+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: EXNPQZ+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 241 FontDescriptor: FontName: EXNPQZ+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: 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