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- Title
Riluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs.
- Authors
Weiss, Steven M; Dahlstrom, Jane E; Saint, David A
- Abstract
The cardiac persistent sodium current ( INaP) presents a novel target for cardiac ischaemic protection. Herein we investigated the effects of the INaP 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.
- Subjects
RILUZOLE; SODIUM channel blockers; ARRHYTHMIA prevention; INFARCTION; ISCHEMIA; MYOCARDIUM; LABORATORY swine; LIGATURE (Surgery)
- Publication
Clinical & Experimental Pharmacology & Physiology, 2013, Vol 40, Issue 12, p856
- ISSN
0305-1870
- Publication type
Article
- DOI
10.1111/1440-1681.12175