Late sodium current inhibition as a new cardioprotective approach.
There is increasing evidence that the late sodium current of the sodium channel in myocytes plays a critical role in the pathophysiology of myocardial ischemia and thus is a potential therapeutic target in patients with ischemic heart disease. Ranolazine, an inhibitor of the late sodium current, reduces the frequency and severity of anginal attacks and ST-segment depression in humans, and unlike other antianginal drugs, ranolazine does not alter heart rate or blood pressure. In experimental animal models, ranolazine has been shown to reduce myocardial infarct size and to improve left ventricular function after acute ischemia and chronic heart failure. This article reviews published data describing the role of late sodium current and its inhibition by ranolazine in clinical and experimental studies of myocardial ischemia.
Hale
Sharon L
SL
The Heart Institute of Good Samaritan Hospital, Los Angeles, CA 90017, USA; The Keck School of Medicine, Division of Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90017, USA.
Shryock
John C
JC
Cardiovascular Therapeutics, Inc, 1651 Page Mill Road, Palo Alto, CA 94304, USA. Electronic address: john.shryock@cvt.com.
Belardinelli
Luiz
L
Cardiovascular Therapeutics, Inc, 1651 Page Mill Road, Palo Alto, CA 94304, USA.
Sweeney
Michael
M
Depomed, Inc., 1360 O'Brien Drive, Menlo Park, CA 94025, USA.
Kloner
Robert A
RA
The Heart Institute of Good Samaritan Hospital, Los Angeles, CA 90017, USA; The Keck School of Medicine, Division of Cardiovascular Medicine, University of Southern California, Los Angeles, CA 90017, USA.
D000083:Acetanilides / Q000494:pharmacology* / Q000627:therapeutic use; D000787:Angina Pectoris / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D000069458:Ranolazine; D012964:Sodium / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015222:Sodium Channels / Q000378:metabolism*
D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012964:Sodium; D000069458:Ranolazine