Show simple item record

Pharmacologic inhibition of the mitochondrial Na+/Ca2+ exchanger protects against ventricular arrhythmias in a porcine model of ischemia-reperfusion

dc.contributor.authorStefania Sventzouri
dc.contributor.authorIoannis Nanas
dc.contributor.authorStyliani Vakrou
dc.contributor.authorChris Kapelios
dc.contributor.authorVasilios Sousonis
dc.contributor.authorTitika Sfakianaki
dc.contributor.authorApostolos Papalois
dc.contributor.authorAntonis S. Manolis
dc.contributor.authorJohn N. Nanas
dc.contributor.authorKonstantinos Malliaras
dc.contributor.other3rd Department of Cardiology, University of Athens School of Medicine, 11 527, Athens, Greece
dc.contributor.other3rd Department of Cardiology, University of Athens School of Medicine, 11 527, Athens, Greece
dc.contributor.other3rd Department of Cardiology, University of Athens School of Medicine, 11 527, Athens, Greece
dc.contributor.other3rd Department of Cardiology, University of Athens School of Medicine, 11 527, Athens, Greece
dc.contributor.other3rd Department of Cardiology, University of Athens School of Medicine, 11 527, Athens, Greece
dc.contributor.other3rd Department of Cardiology, University of Athens School of Medicine, 11 527, Athens, Greece
dc.contributor.otherExperimental Research Center, ELPEN Pharmaceuticals, Athens, Greece
dc.contributor.other3rd Department of Cardiology, University of Athens School of Medicine, 11 527, Athens, Greece
dc.contributor.other3rd Department of Cardiology, University of Athens School of Medicine, 11 527, Athens, Greece
dc.contributor.other3rd Department of Cardiology, University of Athens School of Medicine, 11 527, Athens, Greece; Corresponding author. Konstantinos Malliaras, 3rd Department of Cardiology, University of Athens School of Medicine, 67 Mikras Asias Street, 11 527, Athens, Greece. Tel: +30 210 8236877 Fax: +30 210 7789901.
dc.date.accessioned2018-10-24T02:16:44Z
dc.date.available2025-10-02T03:00:55Z
dc.date.issued01-07-2018
dc.identifier.issn-
dc.identifier.urihttp://www.sciencedirect.com/science/article/pii/S1109966617305018
dc.description.abstractBackground: The mitochondrial Na+/Ca2+ exchanger (mNCX) has been implicated in the pathogenesis of arrhythmogenicity and myocardial reperfusion injury, rendering its inhibition a potential therapeutic strategy. We examined the effects of CGP-37157, a selective mNCX inhibitor, on arrhythmogenesis, infarct size (IS), and no reflow area (NRA) in a porcine model of ischemia-reperfusion. Methods: Forty pigs underwent myocardial ischemia for 60 minutes, followed by 2 hours of reperfusion. Animals were randomized to receive intracoronary infusion of 0.02 mg/kg CGP-37157 or vehicle, either before ischemia (n=17) or before reperfusion (n=17). Animals were monitored for arrhythmias. Myocardial area at risk (AR), IS, and NRA were measured by histopathology. Results: AR, NRA, and IS were comparable between groups. Administration of CGP-37157 before ischemia resulted in the following: (a) suppression of ventricular tachyarrhythmias (events/pig: 1.5±1.1 vs 3.5±1.9, p=0.014), (b) easier cardioversion of ventricular tachyarrhythmias (defibrillations required for cardioversion of each episode: 2.6±2.3 vs 6.2±2.1, p=0.006), and (c) decreased maximal depression of the J point (0.75±0.27 mm vs 1.75±0.82 mm, p=0.007), compared to controls. Administration of CGP-37157 before reperfusion expedited ST-segment resolution; complete ST-segment resolution within 30 minutes of reperfusion was observed in 7/8 CGP-37157-treated animals versus 1/9 controls (p=0.003). Conclusions: In a porcine model of myocardial infarction, intracoronary administration of CGP-37157 did not decrease IS or NRA. However, it suppressed ventricular arrhythmias, decreased depression of the J point during ischemia and expedited ST-segment resolution after reperfusion. These findings motivate further investigation of pharmacologic mNCX inhibition as a potential therapeutic strategy to suppress arrhythmias in the injured heart. Keywords: Ischemia-reperfusion injury, Myocardial infarction, Arrhythmias, Mitochondrial Na+/Ca2+ exchanger, CGP-37157
dc.format-
dc.language.isoEN
dc.publisherElsevier
dc.relation.uri['https://scindeks.ceon.rs/InstructionForAuthors.aspx?issn=0040-2176', 'https://scindeks.ceon.rs/journalDetails.aspx?issn=0040-2176&lang=en', 'https://scindeks.ceon.rs/Portrait.aspx?issn=0040-2176']
dc.rightsCC BY
dc.subject['geology', 'mining', 'electrical engineering', 'mechanical engineering', 'civil engineering', 'new materials', 'Engineering (General). Civil engineering (General)', 'TA1-2040']
dc.subject.lccDiseases of the circulatory (Cardiovascular) system
dc.titlePharmacologic inhibition of the mitochondrial Na+/Ca2+ exchanger protects against ventricular arrhythmias in a porcine model of ischemia-reperfusion
dc.typeArticle
dc.description.pages217-222
dc.description.doi10.1016/j.hjc.2017.12.009
dc.title.journalHellenic Journal of Cardiology
dc.identifier.e-issn-
dc.identifier.oaioai:doaj.org/journal:182b57fec3734d46a08bff6ba0fee949
dc.journal.infoVolume 59, Issue 4


This item appears in the following Collection(s)

Show simple item record