ischemia-reperfusion injury in estrogen receptor-␣ knockout and wild-type mice. Am J Physiol Heart Circ Physiol 278: H1640-H1647, 2000.-We investigated the function of estrogen receptor-␣ in global myocardial ischemia and reperfusion injury in male estrogen receptor-␣ knockout (ERKO) and wild-type mice. Mouse hearts were subjected to 45 min of global ischemia followed by 180 min of reperfusion. The hearts were excised, cannulated, and maintained in a chilled (4°C) cardioplegia solution until

more »

... m (37°C) oxygenated Krebs-Henseleit bicarbonate buffer was perfused through the coronary arteries. ERKO hearts started beating later and had a higher incidence of ventricular fibrillation and/or tachycardia than control hearts. Coronary flow rate was significantly lower in ERKO hearts during the 90-and 120-min periods of reperfusion. Ca 2ϩ accumulation was significantly greater following 30, 90, 120, 150, and 180 min of reperfusion in ERKO hearts. Nitrite production was significantly less in ERKO hearts following 90, 120, and 150 min of reperfusion. Myocardial reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide was significantly lower in experimental ERKO hearts. Marked interstitial edema and contraction bands were seen in hematoxylin-eosin-stained sections of ischemia-reperfused ERKO hearts but not in control tissues. Hematoxylin-basic fuchsin-picric acid-stained sections from experimental ERKO hearts had fewer viable myocytes compared with controls. Transmission electron microscopy revealed swollen and fragmented mitochondria with amorphous and granular bodies, loss of matrix, and rupture of cristae in experimental ERKO hearts. This is the first demonstration that estrogen receptor-␣ plays a cardioprotective role in ischemia-reperfusion injury in males. calcium; nitric oxide; mitochondrial function; myocardial ultrastructure THE RISK OF CORONARY HEART disease in women between puberty and menopause is much lower than that in age-matched men, but this significant gender difference diminishes when postmenopausal women and men of similar age are compared (35). Anecedotal evidence suggests that premenopausal women withstand elective ischemia-reperfusion injury, i.e., cardio- The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.