Effect of testosterone on post-myocardial infarction remodeling and function.
BACKGROUND
Men and women are differently affected by coronary artery disease, suggesting an important role of sex steroids. Moreover, testosterone (T) treatment is increasingly used in elderly males. Therefore, we examined effects of chronic anabolic T administration on left ventricular (LV) remodeling after myocardial infarction (MI).


METHODS
Adult male rats were treated with intramuscular placebo, testosterone undecanoate (T), or were orchiectomized. After 2 weeks, animals underwent sham-operation (sham) or left coronary artery ligation. Left ventricular remodeling and function was assessed by serial magnetic resonance imaging (MRI) at weeks 2 and 8 and hemodynamic investigation at week 8.


RESULTS
In sham operated animals T administration increased serum T levels and led to cardiac hypertrophy, but not to an upregulation of ANP mRNA. The alpha/beta-MHC ratio was significantly higher after T treatment due to an increase in alpha-MHC. As a potential mechanism for this "physiologic" form of hypertrophy, IGF-1 mRNA expression was significantly increased in T treated animals. After coronary artery ligation, infarct size and mortality were similar among the groups. Left ventricular hypertrophy was enhanced by T treatment. However, in vivo LV end-diastolic pressure and wall stress were decreased by T, whereas other hemodynamic parameters (mean arterial pressure, cardiac output, etc.) remained unchanged.


CONCLUSIONS
Chronic anabolic T treatment led to a specific "physiologic" pattern of myocardial hypertrophy with a significant increase in LV weight, but without differences in ANP and with an upregulation in alpha/beta-MHC, possibly mediated by IGF-1. Testosterone treatment had no detrimental effects following MI. Reduced wall stress and LVEDP may even improve long-term outcome.
Nahrendorf
Matthias
M
Medical University Hospital Wuerzburg, Josef-Schneider-Strasse 2, 97080 Wuerzburg, Germany.
Frantz
Stefan
S
Hu
Kai
K
von zur Mühlen
Constantin
C
Tomaszewski
Maria
M
Scheuermann
Heidi
H
Kaiser
Ralf
R
Jazbutyte
Virginija
V
Beer
Stephanie
S
Bauer
Wolfgang
W
Neubauer
Stefan
S
Ertl
Georg
G
Allolio
Bruno
B
Callies
Frank
F
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects*
D012333:RNA, Messenger; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; C010792:testosterone undecanoate