Potential application of late sodium current blockade in the treatment of heart failure and atrial fibrillation.
The cardiac action potential consists of the sequential activation of various ion channels in a precisely orchestrated manner. Pathologic alterations of ion channel currents disrupt this coordinated behavior and have been linked to arrhythmias, such as atrial fibrillation, as well as to heart failure. The late sodium current is increased in the ventricular myocytes in patients with heart failure and can result in contractile dysfunction. The most likely mechanism whereby elevated intracellular Na+ levels may lead to heart failure is through calcium overload. Sodium channel blockade is a proven strategy in the treatment of atrial fibrillation. Although all class I antiarrhythmic drugs inhibit the sodium current, ranolazine has been shown to be a more specific and potent blocker of the late sodium current. In clinical trials, ranolazine has significantly decreased episodes of nonsustained ventricular tachycardia and supraventricular tachycardia as compared with placebo.
Doshi
Darshan
D
Division of Cardiology, Department of Medicine, Columbia University's College of Physicians and Surgeons, New York, NY, USA.
Morrow
John P
JP
D000083:Acetanilides / Q000627:therapeutic use*; D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use*; D000069458:Ranolazine; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome
D000083:Acetanilides; D000889:Anti-Arrhythmia Agents; D010879:Piperazines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012964:Sodium; D000069458:Ranolazine