The effect of chronic exogenous androgen on myocardial function following acute ischemia-reperfusion in hosts with different baseline levels of sex steroids.
BACKGROUND
Gender differences exist in the myocardial response to acute ischemia/reperfusion (I/R) injury and may be attributed to the effects of the sex hormones estrogen and testosterone. The role of estrogen in myocardial injury has been extensively studied but little information exists regarding the myocardial involvement of testosterone. Based on the deleterious effects of chronic endogenous and acute testosterone exposure observed in our previous studies, we postulated that chronic exogenous testosterone administration would also exhibit deleterious effects on myocardial function following I/R.


METHODS
Langendorff perfused rat hearts were subjected to 25 min ischemia, 40 min reperfusion, and left ventricular developed pressure (LVDP) was recorded. Control and 5alpha-dihydrotestosterone (DHT) treated groups each consisted of normal males, castrated males, ovariectomized (OVX) females, and senescent females. P < 0.05 = significant.


RESULTS
Chronic DHT replacement therapy showed no difference in functional ischemic recovery as measured by LVDP after 40 min reperfusion in castrated males (65.1 +/- 8.13% versus 66.3 +/- 4.54%), OVX females (64.5 +/- 10.6% versus 50.2 +/- 5.97%), and senescent females (42.1 +/- 0.04% versus 41 +/- 0.05%). Interestingly, LVDP was greater in DHT treated males than control males after I/R (65.2 +/- 8.20% versus 47.6 +/- 5.19%). Also, DHT treatment resulted in significantly increased recovery of LVDP after only 10 min reperfusion in castrated males, OVX females, and senescent females compared with their untreated counterparts (54.8 +/- 11.9% versus 32.9 +/- 5.75%, 66.7 +/- 11.5% versus 43.1 +/- 8.15%, 53.4 +/- 10.1% versus 32.9 +/- 5.75%, respectively).


CONCLUSIONS
Contrary to the adverse effects we observed in earlier studies with both endogenous and brief exogenous testosterone in myocardium injured by I/R, the present study revealed that chronic exogenous testosterone neither improved nor worsened myocardial functional recovery following 25 min ischemia and 40 min reperfusion.
Nam
Un Hui
UH
Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Wang
Meijing
M
Crisostomo
Paul R
PR
Markel
Troy A
TA
Lahm
Tim
T
Meldrum
Kirstan K
KK
Lillemoe
Keith D
KD
Meldrum
Daniel R
DR
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007511:Ischemia; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology*; D013739:Testosterone / Q000494:pharmacology
D000728:Androgens; D012739:Gonadal Steroid Hormones; D013196:Dihydrotestosterone; D013739:Testosterone