Document Detail

TVP1022 attenuates cardiac remodeling and kidney dysfunction in experimental volume overload-induced congestive heart failure.
MedLine Citation:
PMID:  21558446     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Despite the availability of many pharmacological and mechanical therapies, the mortality rate among patients with congestive heart failure (CHF) remains high. We tested the hypothesis that TVP1022 (the S-isomer of rasagiline; Azilect), a neuroprotective and cytoprotective molecule, is also cardioprotective in the settings of experimental CHF in rats.
METHODS AND RESULTS: In rats with volume overload-induced CHF, we investigated the therapeutic efficacy of TVP1022 (7.5 mg/kg) on cardiac function, structure, biomarkers, and kidney function. Treatment with TVP1022 for 7 days before CHF induction prevented the increase in left ventricular end-diastolic area and end-systolic area, and the decrease in fractional shortening measured 14 days after CHF induction. Additionally, TVP1022 pretreatment attenuated CHF-induced cardiomyocyte hypertrophy, fibrosis, plasma and ventricular B-type natriuretic peptide levels, and reactive oxygen species expression. Further, in CHF rats, TVP1022 decreased cytochrome c and caspase 3 expression, thereby contributing to the cardioprotective efficacy of the drug. TVP1022 also enhanced the urinary Na(+) excretion and improved the glomerular filtration rate. Similar cardioprotective effects were obtained when TVP1022 was given to rats after CHF induction.
CONCLUSIONS: TVP1022 attenuated the adverse functional, structural, and molecular alterations in CHF, rendering this drug a promising candidate for improving cardiac and renal function in this disease state.
Zaid A Abassi; Yaron D Barac; Sawa Kostin; Ariel Roguin; Elena Ovcharenko; Hoda Awad; Ayelet Blank; Orit Bar-Am; Tamar Amit; Jutta Schaper; Moussa Youdim; Ofer Binah
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-05-10
Journal Detail:
Title:  Circulation. Heart failure     Volume:  4     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-20     Completed Date:  2011-09-15     Revised Date:  2011-10-27    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  463-73     Citation Subset:  IM    
Department of Physiology, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
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MeSH Terms
Cardiotonic Agents / pharmacology*,  therapeutic use
Caspase 3 / metabolism
Cytochromes c / metabolism
Disease Models, Animal
Fibrosis / prevention & control
Glomerular Filtration Rate / drug effects,  physiology
Heart Failure / drug therapy,  metabolism,  physiopathology*
Hypertrophy / prevention & control
Indans / pharmacology*,  therapeutic use
Kidney / drug effects*,  physiopathology*
Myocytes, Cardiac / pathology
Natriuretic Peptide, Brain / metabolism
Neuroprotective Agents / pharmacology*,  therapeutic use
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Ventricular Remodeling / drug effects*,  physiology
Reg. No./Substance:
0/Cardiotonic Agents; 0/Indans; 0/Neuroprotective Agents; 0/Reactive Oxygen Species; 114471-18-0/Natriuretic Peptide, Brain; 1875-50-9/rasagiline; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3

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

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