Enhancement of post-ischemic myocardial function by chronic 17 beta-estradiol treatment: Role of alterations in glucose metabolism

This study was designed to assess the effects of chronic estrogen replaceme nt therapy on mechanical function and glucose utilization in aerobic and po st-ischemic hearts, Ovariectomized female rats were either untreated or wer e treated subcutaneously with 17 beta-estradiol (0.25 mg 21-day slow releas e pellets). After 14 days, when serum concentrations of 17 beta-estradiol w ere 3.8 +/- 0.8 and 148 +/- 15 pg/ml, respectively, hearts were isolated an d perfused in working mode with Krebs-Henseleit solution containing 1.2 mM palmitate and 11 mM [5-H-3/U-C-14]glucose. Hearts were perfused aerobically (60 min) and then subjected to low-now ischemia (0.5 ml/min, 60 min) follo wed by reperfusion (30 min). During reperfusion, hearts from rats treated c hronically with 17 beta-estradiol had an improved (two-fold) recovery of me chanical function. 17 beta-estradiol (400 pM, 109 pg/ml), when present acut ely in heart perfusate during ischemia and reperfusion, did not improve rec overy. Chronic 17 beta-estradiol increased glucose oxidation during reperfu sion as well as during aerobic perfusion but had no effect on glycolysis. C hronic 17 beta-estradiol also altered post-ischemic glycogen metabolism and increased glycogen content and glycogen synthase activity at the end of re perfusion. As stimulation of glucose oxidation has been shown previously to be cardioprotective, and as the enhanced rate of glucose oxidation was not simply a consequence of enhanced recovery of mechanical function, alterati ons in glycogen and glucose utilization may contribute to the direct cardio protective effects of chronic estrogen treatment.