Abstract
We tested the hypothesis that chronic testosterone treatment would promote a cardioprotective
phenotype against ischemia/reperfusion (I/R) injury. For this study, 3-month-old F344
male rats underwent sham-surgery, orchiectomy (ORX), or ORX plus 21 days testosterone
treatment (1.0 mg testosterone/day). At sacrifice, cardiac performance was assessed
in a working heart model of I/R (25 min of global ischemia and 45 min of reperfusion).
ORX reduced serum testosterone by ∼98% and testosterone administration elevated serum
testosterone to a concentration of 4.6-fold over that of Sham-operated controls (p<0.05).
ORX did not significantly impair recovery of cardiac performance following I/R, but
did increase cardiac release of lactate dehydrogenase (LDH) during pre- and post-ischemia
(p<0.05). Testosterone administration prevented the ORX-induced increase in LDH during
both pre- and post-ischemia and increased post-ischemic recovery of aortic flow, cardiac
output, cardiac work, left ventricular developed pressure, and contractility (p<0.05)
during reperfusion. Testosterone administration also increased left ventricular expression
of catalase, but did not affect the expression of manganese superoxide dismutase,
glutathione peroxidase, or sarcolemmal KATP channel protein Kir6.2. Neither circulating nor cardiac concentrations of estradiol
were altered by either treatment. We conclude that administration of high-dose testosterone
confers cardioprotection through yet to be identified androgen-dependent mechanism(s).
Key words
testosterone - ischemia - reperfusion - cardioprotection
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Correspondence
S. E. BorstPhD
Malcom Randall VA Medical Center
GRECC – 182
1601 SW Archer Road
Gainesville
FL 32608-1197
USA
Telefon: +1/352/374 61 14
Fax: +1/352/374 61 42
eMail: seborst@ufl.edu
