Abstract:
BACKGROUND:The antianginal agent ranolazine (R) has shown some promise as an antiarrhythmic agent but its mechanism of action is not known. Previously, we have shown that R suppresses ventricular arrhythmias at a concentration >10 μM that may affect multiple ion currents including IKr. PURPOSE:The present study was carried out to determine the effects of low dose (4 μM) of R that primarily inhibits late I(Na) on ischemia/reperfusion induced ventricular arrhythmias. METHODS:We subjected 20 anesthetized rats to 5 min of proximal left coronary artery occlusion followed by 5 min of reperfusion. Rats were randomized to vehicle control (C; n = 10) versus low dose R (n = 10; 3.33 mg/kg i.v. bolus plus 3.2 mg/kg/h R started 20 min prior to occlusion, which yields a concentration of 4 μM, within the known level that blocks late Na channels but well below the level that has effect on IKr or peak I(Na)). Reperfusion-induced arrhythmias were quantitated by electrocardiographic monitoring. RESULTS:In the C group 9/10 rats developed any arrhythmias versus 3/10 in the R group (P = 0.02); 6/10 developed ventricular tachycardia (VT) in the C group versus 0/10 in the R group (P = 0.01). The median number of episodes of VT were 1.5 in the C group versus 0 in the R group (P = 0.005). Sustained VT (>10 sec) occurred in 3/10 C and 0/10 in R (P = 0.21). The median duration of VT was 1.8 seconds in C versus 0 in R (P = 0.005). Ventricular fibrillation occurred in 1/10 in C and 0 in R. Ventricular premature beats (VPBs) occurred in 9/10 C and 3/10 R rats (P = 0.02). The median number of VPBs was 5.5 in the C group versus 0 in R group (P = 0.01). The ischemic risk zones were equivalent in the C and R groups (35 ± 3% and 32 ± 3% of the left ventricle, respectively). CONCLUSIONS:In conclusion, data show that the marked antiarrhythmic effect of R in the setting of acute ischemia/reperfusion occurs at low doses consistent with inhibition of late I(Na) .
journal_name
Cardiovasc Therjournal_title
Cardiovascular therapeuticsauthors
Kloner RA,Dow JS,Bhandari Adoi
10.1111/j.1755-5922.2010.00203.xsubject
Has Abstractpub_date
2011-08-01 00:00:00pages
e36-41issue
4eissn
1755-5914issn
1755-5922pii
CDR203journal_volume
29pub_type
杂志文章abstract:INTRODUCTION:The effectiveness of statin pretreatment in reducing the incidence of contrast-induced nephropathy (CIN) has been examined in some observational and randomized studies, yielding controversial results. AIM:This study sought to evaluate the role of atorvastatin in prevention of CIN in diabetic patients with...
journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,随机对照试验
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,meta分析
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Cardiovascular therapeutics
pub_type: 历史文章,杂志文章,评审
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更新日期:2009-07-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,meta分析,评审
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pub_type: 杂志文章,meta分析,评审
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1111/1755-5922.12182
更新日期:2016-06-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章
doi:10.1111/1755-5922.12277
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,随机对照试验
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更新日期:2015-02-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,meta分析,评审
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更新日期:2017-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2017-04-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章
doi:10.1111/1755-5922.12027
更新日期:2013-12-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,评审
doi:10.1111/j.1755-5922.2008.00070.x
更新日期:2009-04-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1111/1755-5922.12032
更新日期:2013-12-01 00:00:00
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pub_type: 杂志文章,meta分析,评审
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pub_type: 杂志文章,评审
doi:10.1111/j.1527-3466.2007.00038.x
更新日期:2008-04-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章
doi:10.1111/1755-5922.12113
更新日期:2015-06-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,meta分析
doi:10.1155/2020/3987065
更新日期:2020-04-23 00:00:00
abstract:AIMS:Data on the clinical impact of gender in "real-life" patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), receiving clopidogrel, prasugrel, or ticagrelor are limited. We aimed to investigate sex-based differences in clinical outcome of those patients. METHODS:In a prosp...
journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1111/1755-5922.12270
更新日期:2017-08-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,评审
doi:10.1111/j.1755-5922.2010.00161.x
更新日期:2010-08-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章
doi:10.1111/1755-5922.12111
更新日期:2015-04-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,评审
doi:10.1111/j.1755-5922.2010.00216.x
更新日期:2010-10-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,评审
doi:10.1111/j.1755-5922.2010.00151.x
更新日期:2011-10-01 00:00:00
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journal_title:Cardiovascular therapeutics
pub_type: 杂志文章
doi:10.1111/1755-5922.12046
更新日期:2013-12-01 00:00:00
abstract:AIMS:We investigated the relative pharmacokinetics, pharmacodynamics, and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab following injection at three different sites. METHODS:Sixty healthy subjects (39 male, 21 female; age 20-45 years) were randomized to receive a single subcu...
journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1111/1755-5922.12093
更新日期:2014-12-01 00:00:00
abstract:BACKGROUND:The origin of dyspnea in chronic heart failure (HF) is multifactorial, and excessive ventilation is thought to play a role in inducing this symptom. Chemosensivity is augmented in HF, correlates with increased pulmonary ventilation (VE), and is an adverse prognostic marker. Despite increased blood levels of ...
journal_title:Cardiovascular therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1755-5922.2011.00297.x
更新日期:2013-04-01 00:00:00