Riluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs

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dc.contributor.authorWeiss, S.
dc.contributor.authorDahlstrom, J.
dc.contributor.authorSaint, D.
dc.date.issued2013
dc.description.abstractThe cardiac persistent sodium current (IN aP ) presents a novel target for cardiac ischaemic protection. Herein we investigated the effects of the IN aP blocker riluzole in a pig model of regional myocardial ischaemia. Landrace or Large White pigs were subjected to 3 h ligation of the left anterior descending coronary artery (LAD). Pigs received either saline (500 mL/h, i.v.) throughout the experiment (control; n = 7) or riluzole (2 mg/kg in 2 mL propylene glycol in 100 mL saline, i.v.; RIL; n = 7) between 15 and 5 min prior to ligation. The arrhythmia score was calculated in 5 min epochs. Myocardial damage was assessed using epicardial image analysis and histological sectioning. In the control group, all seven pigs developed premature ventricular contractions (PVC), seven developed non-sustained arrhythmias and six of seven developed sustained arrhythmias. Of the sustained arrhythmias, 23 of 28 instances were initiated by R-on-T extrasytoles (extrasystoles within the vulnerable period that can trigger re-entrant arrhythmias). In the RIL group, all seven pigs developed PVC, six of seven developed non-sustained arrhythmias and only three developed sustained arrhythmias, of which two of five instances were R-on-T initiated. The riluzole-treated pigs exhibited less myocardial damage than pigs in the control group (65% smaller surface area (P = 0.008) on gross epicardial inspection, 51% less oedema (P = 0.01), 53% less fibre waviness (P = 0.029) assessed by haematoxylin and eosin staining and 79% fewer fragmented nuclei (P = 0.009) assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling). In conclusion, riluzole significantly reduced Phase 2 (the period associated with irreversible damage) ischaemic R-on-T triggered and non-R-on-T arrhythmias and myocardial damage occurring during the 3 h period of regional ischaemia.
dc.description.statementofresponsibilitySteven M Weiss, Jane E Dahlstrom and David A Saint
dc.identifier.citationClinical and Experimental Pharmacology and Physiology, 2013; 40(12):856-863
dc.identifier.doi10.1111/1440-1681.12175
dc.identifier.issn1440-1681
dc.identifier.issn1440-1681
dc.identifier.urihttp://hdl.handle.net/2440/81901
dc.language.isoen
dc.publisherWiley-Blackwell Publishing Asia
dc.rights© 2013 Wiley Publishing Asia Pty Ltd.
dc.source.urihttps://doi.org/10.1111/1440-1681.12175
dc.subjectarrhythmia
dc.subjectheart
dc.subjectinfarction
dc.subjectischaemia
dc.subjectmyocardium
dc.subjectpathology
dc.subjectriluzole
dc.titleRiluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs
dc.typeJournal article
pubs.publication-statusPublished

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