Cardiac Magnetic Resonance Assessment Of Interstitial Myocardial Fibrosis And Cardiomyocyte Hypertrophy In Hypertensive Mice Treated With Spironolactone.


Autoria(s): Coelho-Filho, Otavio R; Shah, Ravi V; Neilan, Tomas G; Mitchell, Richard; Moreno, Heitor; Kwong, Raymond; Jerosch-Herold, Michael
Contribuinte(s)

UNIVERSIDADE DE ESTADUAL DE CAMPINAS

Data(s)

01/06/2014

27/11/2015

27/11/2015

Resumo

Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR). Mice were randomized to l-nitro-ω-methyl ester (l-NAME, 3 mg/mL in water; n=22), or l-NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (τic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of l-NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and τic compared with placebo-treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and l-NAME (l-NAME+S) showed less concentric remodeling, and a lower myocardial ECV and τic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43 ± 0.09 for l-NAME versus 0.25 ± 0.03 for l-NAME+S, P<0.001; τic: 0.42 ± 0.11 for l-NAME groups versus 0.12 ± 0.05 for l-NAME+S group). Mice treated with a combination of l-NAME and spironolactone were similar to placebo-treated controls at 7 weeks. Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure-overload, furthering our understanding of HF progression.

3

e000790

Identificador

Journal Of The American Heart Association. v. 3, n. 3, p. e000790, 2014-Jun.

2047-9980

10.1161/JAHA.114.000790

http://www.ncbi.nlm.nih.gov/pubmed/24965024

http://repositorio.unicamp.br/jspui/handle/REPOSIP/201515

24965024

Idioma(s)

eng

Relação

Journal Of The American Heart Association

J Am Heart Assoc

Direitos

fechado

© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Fonte

PubMed

Palavras-Chave #Animals #Cardiac Imaging Techniques #Cardiomegaly #Fibrosis #Heart #Hypertension #Magnetic Resonance Imaging #Mice #Myocardium #Myocytes, Cardiac #Ng-nitroarginine Methyl Ester #Receptors, Mineralocorticoid #Spironolactone #Stroke Volume #Cardiac Magnetic Resonance Imaging #Hypertension #Hypertrophy/remodeling
Tipo

Artigo de periódico