Document Detail


Ranolazine as a cardioplegia additive improves recovery of diastolic function in isolated rat hearts.
MedLine Citation:
PMID:  19752362     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Ranolazine (Ran), an antianginal agent, inhibits late Na(+) current. The purpose of this study was to determine whether there was an added benefit of adding Ran to cardioplegia (CP) in a model of global ischemia/reperfusion. METHODS AND RESULTS: Isolated rat hearts were Langendorff-perfused and exposed to 40-minute normothermic, cardioplegic global ischemia and 30 minutes of reperfusion. Before ischemia and during reperfusion, hearts were treated with no drug (control) or with the late Na(+) current inhibitors Ran (5 micromol/L) or tetrodotoxin (1 micromol/L). Ischemic cardioplegic arrest led to an increase of left ventricular end-diastolic pressure (LVEDP) by > or =20 mm Hg (ie, cardiac contracture). Ten out of 11 hearts treated with CP alone developed contracture, whereas 6 out of 11 hearts treated with CP plus Ran developed contracture. Ran added to CP reduced LVEDP at the end of ischemia from 41+/-5 mm Hg in CP alone to 26+/-3 mm Hg in CP plus Ran (P=0.024). Area under the curve for LVEDP during the entire ischemic period was also smaller in CP plus Ran versus CP alone. The percent increase (from baseline) of LVEDP measured at the end of 30-minute reperfusion was smaller for CP plus Ran (66+/-18%) versus CP alone (287+/-90%; P=0.035). The area under the curve for LVEDP during reperfusion was smaller in CP plus Ran versus CP alone. Tetrodotoxin (1 micromol/L) also reduced cardiac contracture during ischemia/reperfusion, compared to CP alone. CONCLUSIONS: Our results suggest that Ran may have therapeutic potential as an adjunct to CP and further support a protective role of Na(+) current inhibition during ischemia/reperfusion.
Authors:
Hyosook Hwang; Joseph M Arcidi; Sharon L Hale; Boris Z Simkhovich; Luiz Belardinelli; Arvinder K Dhalla; John C Shryock; Robert A Kloner
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  120     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-15     Completed Date:  2009-10-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S16-21     Citation Subset:  AIM; IM    
Affiliation:
The Heart Institute, Good Samaritan Hospital, Los Angles, CA 90017, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetanilides / pharmacology*
Angina Pectoris / drug therapy*
Animals
Diastole / drug effects*
Female
Heart Arrest, Induced*
Myocardial Contraction / drug effects
Myocardial Ischemia / physiopathology
Piperazines / pharmacology*
Rats
Rats, Sprague-Dawley
Sodium / metabolism
Tetrodotoxin / pharmacology
Chemical
Reg. No./Substance:
0/Acetanilides; 0/Piperazines; 110445-25-5/ranolazine; 4368-28-9/Tetrodotoxin; 7440-23-5/Sodium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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