the persistent sodium current blocker riluzole is antiarrhythmic and anti-ischaemic in a pig model of acute myocardial infarction持续钠电流阻断剂利鲁唑是抗心律失常的和非常猪急性心肌梗死模型.pdfVIP

The Persistent Sodium Current Blocker Riluzole Is Antiarrhythmic and Anti-Ischaemic in a Pig Model of Acute Myocardial Infarction 1 2 Steven M. Weiss , David A. Saint * 1 Australian National University, Canberra, Australia, 2 University of Adelaide, Adelaide, Australia Abstract Background: The potential of the cardiac persistent sodium current as a target for protection of the myocardium from ischaemia and reperfusion injury is gaining increasing interest. We have investigated the anti-ischaemic and antiarrhythmic effects of riluzole, a selective INaP blocker, in an open chest pig model of infarction. Methods and Principal Findings: The left anterior descending coronary artery (LAD) was ligated in 27 anesthetised pigs (landrace or large white, either sex, 20–35 kg) which had received riluzole (8 mg/kg IP; n = 6), lidocaine (2.5–12 mg/kg bolus plus 0.05–0.24 mg/kg/min; n = 11) or vehicle (n = 10) 50 min prior. Arrhythmias could be delineated into phase 1a (0 to 20 min), phase 1b (20 to 50 min) and phase 2 (from 50 min to termination at 180 min) and were classified as premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) (spontaneously reverting within 15 s) or sustained VT or VF (ie. requiring cardioversion at 15 s). Riluzole reduced the average number of all arrhythmias in Phase 2 (PVCs from 484+/ 2119 to 32+/ 213; non sustained arrhythmias from 8.9+/ 24.4 to 0.7+/ 20.5; sustained arrhythmias from 3.9+/ 22.2 to 0.5+/ 20.4); lidocaine reduced the average number of non-sustained and sustained arrhythmias (to 0.4+/ 20.3 and 0.4+/ 20.3 respectively) but not PVCs (to 390+/ 2234). Riluzole and lidocaine reduced the average number of sustained arrhythmias in phase 1b (from 1.8+/ 20.4 to 0.17+/ 20.13 (p,0.0