Premium
Riluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs
Author(s) -
Weiss Steven M,
Dahlstrom Jane E,
Saint David A
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12175
Subject(s) - riluzole , medicine , saline , ventricular fibrillation , anesthesia , cardiology , ligation , glutamate receptor , receptor
Summary The cardiac persistent sodium current ( I N aP ) presents a novel target for cardiac ischaemic protection. Herein we investigated the effects of the I N 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.