Document Detail

Intrapericardial ranolazine prolongs atrial refractory period and markedly reduces atrial fibrillation inducibility in the intact porcine heart.
MedLine Citation:
PMID:  20075744     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Extensive experimental studies and clinical evidence (Metabolic Efficiency with Ranzolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction-36 [MERLIN TIMI-36] trial) indicate potential antiarrhythmic efficacy of the antianginal agent ranolazine. Delivery of agents into the pericardial space allows high local concentrations to be maintained in close proximity to myocardial tissue while systemic effects are minimized. METHODS AND RESULTS: The effects of intrapericardial (IPC) administration of ranolazine (50-mg bolus) on right atrial and right ventricular effective refractory periods (ERP), atrial fibrillation threshold, and ventricular fibrillation threshold were determined in 17 closed-chest anesthetized pigs. IPC ranolazine increased atrial ERP in a time-dependent manner from 129 +/- 5.14 to 186 +/- 9.78 ms (P < 0.01, N = 7) but did not significantly affect ventricular ERP (from 188.3 +/- 4.6 to 201 +/- 4.3 ms (NS, N = 6). IPC ranolazine increased atrial fibrillation threshold from 4.8 +/- 0.8 to 28 +/- 2.3 mA (P < 0.03, N = 6) and ventricular fibrillation threshold (from 24 +/- 3.56 baseline to 29.33 +/- 2.04 mA at 10-20 minutes, P < 0.03, N = 6). No significant change in mean arterial pressure was observed (from 92.8 +/- 7.1 to 74.8 +/- 7.5 mm Hg, P < 0.125, N = 5, at 7 minutes). CONCLUSIONS: IPC ranolazine exhibits striking atrial antiarrhythmic actions as evidenced by increases in refractoriness and in fibrillation inducibility without significantly altering mean arterial blood pressure. Ranolazine's effects on the atria appear to be more potent than those on the ventricles.
Marcelo Carvas; Bruno C G Nascimento; Mariana Acar; Bruce D Nearing; Luiz Belardinelli; Richard L Verrier
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  55     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-07-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  286-91     Citation Subset:  IM    
University of São Paulo School of Medicine, São Paulo, Brazil.
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MeSH Terms
Acetanilides / administration & dosage,  pharmacology*
Anti-Arrhythmia Agents / administration & dosage,  pharmacology*
Atrial Fibrillation / drug therapy*,  physiopathology
Blood Pressure / drug effects
Disease Models, Animal
Piperazines / administration & dosage,  pharmacology*
Refractory Period, Electrophysiological / drug effects
Time Factors
Ventricular Fibrillation / drug therapy*,  physiopathology
Reg. No./Substance:
0/Acetanilides; 0/Anti-Arrhythmia Agents; 0/Piperazines; 110445-25-5/ranolazine

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