Testosterone administration induces protection against global myocardial ischemia

Abstract

We tested the hypothesis that testosterone (T) treatment affords protection against ischemia/reperfusion (I/R) injury. Orchiectomized (ORX) F344 male rats received 1.0 mg T/day for 21 days or exercise training (EX) for 10 days. Treatment groups were: Sham‐operated, ORX, ORX+T and ORX+EX. At sacrifice, cardiac performance was assessed in a working heart model of I/R (25 minutes of global ischemia and 45 minutes of reperfusion). T increased recovery of aortic flow by 2.2‐fold (p < 0.05) and cardiac work by 2.0‐fold (p < 0.05). ORX reduced recovery of left ventricular developed pressure (LVDP) by 42% (p < 0.05). T increased recovery of LVDP by 2.8‐fold and cardiac contractility (+dP/dt) by 45% (p < 0.05). ORX caused a 2.6‐fold increase in pre‐ischemic cardiac release of lactate dehydrogenase (LDH), an effect that was prevented by T (p < 0.05), but not EX. T reduced post‐ischemic release of LDH release by 45% (p < 0.05). EX caused a 13% increase in cardiac expression of MnSOD and T caused a 28% increase in catalase expression. Glutathione peroxidase (GPX) was not affected by either intervention. ORX reduced serum T by ~98% and T administration elevated T 4.6‐fold over Sham (p < 0.05). Serum estrogen was undetectable in all groups. We conclude that that loss of natural T predisposes the heart to increased contractile dysfunction during I/R, and that high‐dose T confers cardioprotection through yet to be identified mechanism(s).