title: Riluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs.
abstract: The 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.
authors.affiliation: Australian National University Medical School, The Canberra Hospital, Canberra, ACT, Australia.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Weiss
authors.forename: Jane E
authors.initials: JE
authors.lastname: Dahlstrom
authors.forename: David A
authors.initials: DA
authors.lastname: Saint
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D054059:Coronary Occlusion / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019782:Riluzole / Q000008:administration & dosage / Q000627:therapeutic use*; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D013552:Swine
chemical_list: D000889:Anti-Arrhythmia Agents; D026941:Sodium Channel Blockers; D019782:Riluzole
keywords: arrhythmia; heart; infarction; ischaemia; myocardium; pathology; riluzole