Mortality rates attributable to coronary heart disease have declined in recent years, possibly related to changes in clinical presentation patterns and use of proven secondary prevention strategies. Chronic stable angina (CSA) remains prevalent, and the goal of treatment is control of symptoms and reduction in cardiovascular events. Ranolazine is a selective inhibitor of the late sodium current...

Introduction Long QT syndrome type 3 (LQT3) results from gain-offunction mutations in the SCN5A gene, which encodes the major cardiac sodium channel, voltage-gated type V alpha subunit (NaV 1.5). Those mutations result in an increase in late sodium channel current, which leads to delayed ventricular repolarization, torsades de pointes (TdP), and sudden death. Traditionally, beta-blockers mexile...

BACKGROUND Antiarrhythmic compounds against atrial fibrillation (AF) often have reduced efficacy and may display cardiac and/or noncardiac toxicity. Efficacy can be improved by combining 2 compounds with distinct mechanisms, and it may be possible to use lower doses of each compound, thereby reducing the likelihood of adverse side effects. The purpose of this study was to investigate whether th...

BACKGROUND Pro-arrhythmic concerns with most anti-arrhythmic agents in patients with significant left ventricular hypertrophy (LVH) limits options when anti-arrhythmic therapy is indicated. Ranolazine, an anti-anginal agent which inhibits late Na+ currents, indirectly causes a decrease in diastolic cardiomyocyte Ca++ levels producing an energy sparing effect. Ranolazine also inhibits triggered ...

Block of Na(+) channel conductance by ranolazine displays marked atrial selectivity that is an order of magnitude higher that of other class I antiarrhythmic drugs. Here, we present a Markovian model of the Na(+) channel gating, which includes activation-inactivation coupling, aimed at elucidating the mechanisms underlying this potent atrial selectivity of ranolazine. The model incorporates exp...

The action mechanism of ranolazine, an antiangina drug, could be at least partly metabolic, including inhibition of fatty acid oxidation and stimulation of glucose utilization in the heart. The purpose of the present work was to investigate if ranolazine affects hepatic carbohydrate metabolism. For this purpose, the hemoglobin-free isolated perfused rat liver was used as the experimental system...

BACKGROUND Several clinical trials have shown that vernakalant is effective in terminating recent onset atrial fibrillation (AF). The electrophysiological actions of vernakalant are not fully understood. METHODS AND RESULTS Here we report the results of a blinded study comparing the in vitro canine atrial electrophysiological effects of vernakalant, ranolazine, and dl-sotalol. Action potentia...

Inhibition of fatty acid oxidation has been reported to be cardioprotective against myocardial ischemic injury; however, recent studies have questioned whether the cardioprotection associated with putative fatty acid oxidation inhibitors, such as ranolazine and trimetazidine, are due to changes in substrate oxidation. Therefore, the goals of this study were to compare the effects of ranolazine ...