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.

Neuroanatomy of the Pig Cardiac Ventricles. A Stereomicroscopic, Confocal and Electron Microscope Study

“…The models remain an essential tool for predicting and preventing these diseases (Zaragoza et al, ). The pig is used to model cardiovascular events: atherosclerosis (Gerrity et al, ), myocardial infarction (Suzuki et al, ), abdominal aortic aneurysm (Molácek et al, ), heart failure (Dixon and Spinale, ), cardiac arrhythmias (Weiss et al, ; Zhang et al, ), heart transplantation (Desrois et al, ), etc. The pig remains a leading model for investigating human cardiovascular diseases due to anatomical and physiological similarities to the human heart.…”

Late Sodium Current Inhibitors as Potential Antiarrhythmic Agents

“…Riluzole also directly inhibits the kainate and NMDA receptors (Debono et al, 1993) as well as potentiates GABA A receptors (He et al, 2002). In anaesthetized pigs, myocardial damage and arrhythmias induced by coronary occlusion has been reduced by riluzole (Weiss et al, 2013). Riluzole has also been found to be anti-ischemic and antiarrhythmic in a pig model of acute myocardial infarction.…”