Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/2226
Title: Low doses of ranolazine and dronedarone in combination exert potent protection against atrial fibrillation and vulnerability to ventricular arrhythmias during acute myocardial ischemia
Authors: VERRIER, Richard L.PAGOTTO, Vitor P. F.KANAS, Alexandre F.SOBRADO, Marcel F.NEARING, Bruce D.ZENG, DewanBELARDINELLI, Luiz
Citation: HEART RHYTHM, v.10, n.1, p.121-127, 2013
Abstract: BACKGROUND Coronary artery disease carries dual risk for atrial tachyarrhythmias and sudden cardiac death. OBJECTIVE To examine whether Low-dose ranolazine and/or dronedarone can protect against vulnerability to atria L fibrillation (AF) and ventricular tachyarrhythmias. METHODS In chloralose-anesthetized, open-chest Yorkshire pigs (n = 15), the proximal segment of Left circumflex (LCx) coronary artery was occluded to reduce flow by 75%. An electrode catheter was positioned on the Left atria L appendage to measure AF threshold (AFT) before and during LCx coronary artery stenosis before and at 1 hour after dronedarone (0.5 mg/kg intravenous bolus over 5 minutes) and/or ranolazine administration (0.6 mg/kg intravenous bolus foLLowed by 0.035 mg/kg/min). RESULTS Before drug administration, LCx coronary artery stenosis Lowered AFT from 25.2 +/- 1.7 mA controL (mean +/- SEM) to 4.9 +/- 1.0 mA baseLine (P < .01). At the Low doses, neither ranolazine (plasma concentration 2.4 +/- 0.6 mu M) nor dronedarone (plasma concentration 20.9 +/- 3.5 nM) atone bunted the ischemia-induced reduction in AFT but were effective together (from 25.2 +/- 1.7 mA controL to 22.0 +/- 3.0 mA during stenosis; P = not significant). AF duration (P < .03) and AF inducibility (P = .012) were reduced by ranolazine and dronedarone together but not by either drug atone. Concurrently, combined but not separate administration bunted the ischemia-induced surge in T-wave heterogeneity, a marker of risk for ventricular tachyarrhythmias (from 43.1 +/- 11.1 mu V controL to 149.7 +/- 15.1 mu V during stenosis, P < .001, compared to 61.7 +/- 13.7 mu V controL to 83.7 +/- 15.8 mu V during stenosis, P = not significant). CONCLUSIONS Combined administration of Low doses of ranolazine and dronedarone exerts a potent antiarrhythmic action on ischemia-induced vulnerability to AF and ventricular tachyarrhythmias due to direct effects on myocardial electrical properties.
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