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EFFECTS OF SPIRONOLACTONE ALONE AND IN ADDITION TO A BETABLOCKER ON MYOCARDIAL HISTOLOGICAL AND ELECTRICAL REMODELING IN CHRONIC SEVERE FAILING RAT HEARTS.
MedLine Citation:
PMID:  22710814     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND:: Aldosterone antagonists (AA) have beneficial effects on ventricular histological and electrical remodeling and improve noradrenaline uptake. Adding an AA to a beta-blocker (BB) further improves cardiac mortality in heart failure (HF) patients. We investigated if adjunction of a BB modifies beneficial effects of spironolactone on different parameters of the ventricular remodeling METHODS:: A severe myocardial infarction (MI) was produced in rats. Three months after surgery, left ventricular (LV) function was assessed by echocardiography. Fifty-five rats with HF were then randomized in 5 groups: sham, MI, and MI treated for 4 weeks with spironolactone (10 mg/kg/day), atenolol (1 mg/kg/day) or both. Holter transducers were implanted to record 24-hour ventricular electrical parameters, mean cycle length (RR) and standard deviation (sd) of RR. Before sacrifice, invasive left ventricular end diastolic pressure (LVEDP) was recorded. LV samples were used for histological analysis and catecholamine assay. RESULTS:: MI rats had significantly increased LVEDP (32±3 versus 14±1 mmHg), LV collagen content (5.8±1.4% versus 3.6±0.7%), ventricular premature complexes (VPCs) (2.5 103±103 versus 30±13), and decreased meanRR (164±2 versus 169±1 ms) and sdRR (3.9±0.2 versus 5.4±0.2 ms) compared to sham. At non-hypotensive doses, spironolactone and atenolol similarly improved LVEDP. Compared to MI, while spironolactone significantly decreased VPCs, LV collagen and noradrenaline contents, and improved meanRR and sdRR, atenolol had only effects on meanRR and sdRR. Addition of atenolol to spironolactone further improved spironolactone effects on all these parameters. CONCLUSION:: AA improved, independently of the cardiac function, histological as well as electrical remodeling after MI. A BB added to an AA did not blunt these beneficial effects; furthermore it improved these effects related to spironolactone.
Authors:
Paul Milliez; Sophie Gomes; Laure Champ-Rigot; Jacques Callebert; Jane-Lise Samuel; Claude Delcayre
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-15
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  -     ISSN:  1533-4023     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1INSERM U942, University Paris-Diderot, Lariboisiere University Hospital, Paris, France. 2Cardiology Department, Caen University Hospital, Normandy, France 3Biochemical Department, Lariboisiere University Hospital, Paris, France.
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