Late sodium current inhibition as a new cardioprotective approach

被引:128
作者
Hale, Sharon L. [2 ,3 ]
Shryock, John C. [1 ]
Belardinelli, Luiz [1 ]
Sweeney, Michael [4 ]
Kloner, Robert A. [2 ,3 ]
机构
[1] Cardiovasc Therapeut Inc, Palo Alto, CA 94304 USA
[2] Hosp Good Samaritan, Inst Heart, Los Angeles, CA 90017 USA
[3] Univ So Calif, Keck Sch Med, Div Cardiovasc Med, Los Angeles, CA 90017 USA
[4] Depomed Inc, Menlo Pk, CA 94025 USA
关键词
late I-Na; late sodium current; ranolazine; ischemia; angina; MERLIN; calcium overload; cardioprotection;
D O I
10.1016/j.yjmcc.2008.03.019
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:954 / 967
页数:14
相关论文
共 111 条
[51]   Hypoxia increases persistent sodium current in rat ventricular myocytes [J].
Ju, YK ;
Saint, DA ;
Gage, PW .
JOURNAL OF PHYSIOLOGY-LONDON, 1996, 497 (02) :337-347
[52]   INACTIVATION-RESISTANT CHANNELS UNDERLYING THE PERSISTENT SODIUM CURRENT IN RAT VENTRICULAR MYOCYTES [J].
JU, YK ;
SAINT, DA ;
GAGE, PW .
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 1994, 256 (1346) :163-168
[53]   LATE SODIUM CURRENT AND ITS CONTRIBUTION TO ACTION-POTENTIAL CONFIGURATION IN GUINEA-PIG VENTRICULAR MYOCYTES [J].
KIYOSUE, T ;
ARITA, M .
CIRCULATION RESEARCH, 1989, 64 (02) :389-397
[54]   Long-term safety of a novel antianginal armant in patients with severe chronic stable angina - The Ranolazine Open Label Experience (ROLE) [J].
Koren, Michael J. ;
Crager, Michael R. ;
Sweeney, Michael .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2007, 49 (10) :1027-1034
[55]   ALLEVIATION OF CONTRACTILE DYSFUNCTION IN ISCHEMIC HEARTS BY SLOWLY INACTIVATING NA+ CURRENT BLOCKERS [J].
LEGRAND, B ;
VIE, B ;
TALMANT, JM ;
CORABOEUF, E ;
JOHN, GW .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1995, 269 (02) :H533-H540
[56]   Evidence that ranolazine behaves as a weak β1- and β2-adrenoceptor antagonist in the rat cardiovascular system [J].
Létienne, R ;
Vié, B ;
Puech, A ;
Vieu, S ;
Le Grand, B ;
John, GW .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2001, 363 (04) :464-471
[57]  
LIU JX, 1993, J PHARMACOL EXP THER, V266, P1247
[58]   NA CHANNELS THAT REMAIN OPEN THROUGHOUT THE CARDIAC ACTION-POTENTIAL PLATEAU [J].
LIU, YM ;
DEFELICE, LJ ;
MAZZANTI, M .
BIOPHYSICAL JOURNAL, 1992, 63 (03) :654-662
[59]   Molecular basis of an inherited epilepsy [J].
Lossin, C ;
Wang, DW ;
Rhodes, TH ;
Vanoye, CG ;
George, AL .
NEURON, 2002, 34 (06) :877-884
[60]  
Ma Ji-Hua, 2004, Shengli Xuebao, V56, P603