Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Belardinelli, L.
Right arrow Articles by Fraser, H.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Belardinelli, L.
Right arrow Articles by Fraser, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

The mechanism of ranolazine action to reduce ischemia-induced diastolic dysfunction

Luiz Belardinelli*, John C. Shryock and Heather Fraser

Pharmacology and Translational Biomedical Research, CV Therapeutics Inc., 3172 Porter Drive, Palo Alto, CA 94304, USA

* Corresponding author. Tel: +1 650 384 8526; fax: +1 650 475 0450. E-mail address: luiz.belardinelli{at}cvt.com

Ischaemia of myocardium is associated with increases in the late sodium current (INa), intracellular sodium and calcium concentrations, calcium overload, and impairment of contractile relaxation (i.e. increased diastolic wall tension). An increase in diastolic wall tension compresses the vasculature and reduces nutritive blood flow, creating a positive feedback system that further impairs myocardial oxygenation and contractile function. Ranolazine reduces the late INa and, is expected to decrease sodium entry into ischaemic myocardial cells. As a consequence, ranolazine is proposed to reduce calcium uptake indirectly via the sodium/calcium exchanger and to preserve ionic homeostasis and reverse ischaemia-induced contractile dysfunction.

Key Words: Late INa • Ischaemia • Diastole • Angina • Calcium overload • Persistent sodium current • Ranolazine


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.