High-dose 17beta-estradiol treatment prevents development of heart failure post-myocardial infarction in the rat.
OBJECTIVE
Prognosis of heart failure remains poor despite therapeutic advances, such as angiotensin converting enzyme inhibition or beta-receptor blockade. Thus, more effective forms of treatment are urgently needed. Since estrogens have been shown to modulate migration and proliferation of cardiac fibroblasts and to modulate the expression of estrogen receptors of cardiomyocytes we examined whether high-dose estrogen treatment can affect post-myocardial infarction left ventricular remodeling.


METHODS
Female rats were treated with 17beta-estradiol (7.5 mg/90 d) or placebo for ten weeks, starting two weeks prior to experimental myocardial infarction. Eight weeks after infarction, in vivo echocardiographic and hemodynamic measurements as well as isolated heart perfusion were performed.


RESULTS
In vivo, chronic estrogen treatment almost completely prevented the development of all signs of heart failure that occur in untreated infarcted hearts, such as increased left ventricular diameters (dilatation), reduced fractional shortening (systolic dysfunction) or increased left ventricular end-diastolic pressure (diastolic dysfunction). In vitro, the right- (indicating structural dilatation) and downward (indicating left ventricular dysfunction) shift of left ventricular pressure-volume curves occurring in untreated infarcted hearts was completely prevented by estrogen.


CONCLUSIONS
High dose estradiol treatment prevented development of post-MI remodeling, as assessed by in vivo and in vitro parameters of LV dysfunction. Estrogen may hold the potential of becoming a new form of heart failure treatment.However, the mechanisms responsible for this striking and unexpected beneficial action of estrogen in heart failure remain to be elucidated.
Beer
Stephanie
S
Medizinische Universitätsklinik, Josef-Schneider-Str. 2, 97080, Würzburg, Germany. s.beer@medizin.uni-wuerzburg.de
Reincke
Martin
M
Kral
Maike
M
Callies
Frank
F
Strömer
Hinrik
H
Dienesch
Charlotte
C
Steinhauer
Sonja
S
Ertl
Georg
G
Allolio
Bruno
B
Neubauer
Stefan
S
D000818:Animals; D001794:Blood Pressure; D018619:Echocardiography, Doppler, Pulsed; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D004958:Estradiol