The purpose of this study was to test whether the susceptibility of the heart to
ischemia/reperfusion injury is modulated by the chronic
estrogen status, i.e., increased with
estrogen deficiency and attenuated by pharmacologic
estrogen supplementation. In addition, the study tested whether
estrogen-dependent changes in mechanical function are associated with alterations of cardiac high-energy
phosphate metabolism. Rats were ovariectomized, not ovariectomized, or ovariectomized and treated with subcutaneous
estrogen pellets (1.5 mg/21 d) (n = 8-11 per group). Three weeks later, hearts were isolated and perfused isovolumically under constant perfusion pressure conditions. Hearts were subjected to 15 min of total global
ischemia (37 degrees C) and 30 min of reperfusion. Simultaneous [31P] nuclear magnetic resonance spectra were recorded throughout this protocol to monitor changes in
ATP,
phosphocreatine, and
inorganic phosphate content. Whereas preischemic values for heart rate, end-diastolic pressure, and coronary flow were not different among groups, left ventricular developed pressure was slightly but significantly decreased in the
estrogen-treated group (p < 0.05). However, treated hearts showed improved recovery of left ventricular developed pressure on reperfusion (89 +/- 4% in control rats, 70 +/- 8% in ovariectomized hearts, and 114 +/- 9% of preischemic values in
estrogen-treated rats). However, changes in
ATP,
phosphocreatine, and
inorganic phosphate during
ischemia were as previously described and were unaffected by chronic
estrogen status. In conclusion, in the isolated
buffer-perfused rat heart,
estradiol treatment caused improved functional recovery after
ischemia/reperfusion injury. This improvement, however, did not include preservation of high-energy
phosphate metabolism. Other potential mechanisms include an
anti-oxidant activity of 17beta-estradiol-and
estrogen-induced alterations in
glucose metabolism.