Myocardial ischemia-reperfusion injury in estrogen receptor-alpha knockoutand wild-type mice

We investigated the function of estrogen receptor-a in global myocardial is chemia and reperfusion injury in male estrogen receptor-a knockout (ERKO) a nd wild-type mice. Mouse hearts were subjected to 45 min of global ischemia followed by 180 min of reperfusion. The hearts were excised, cannulated, a nd maintained in a chilled (4 degrees C) cardioplegia solution until warm ( 37 degrees C) oxygenated Krebs-Henseleit bicarbonate buffer was perfused th rough the coronary arteries. ERKO hearts started beating later and had a hi gher incidence of ventricular fibrillation and/or tachycardia than control hearts. Coronary flow rate was significantly lower in ERKO hearts during th e 90- and 120-min periods of reperfusion. Ca2+ accumulation was significant ly greater following 30, 90, 120, 150, and 180 min of reperfusion in ERKO h earts. Nitrite production was significantly less in ERKO hearts following 9 0, 120, and 150 min of reperfusion. Myocardial reduction of 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide was significantly lower in ex perimental ERKO hearts. Marked interstitial edema and contraction bands wer e seen in hematoxylin-eosin-stained sections of ischemia-reperfused ERKO he arts but not in control tissues. Hematoxylin-basic fuchsin-picric acid-stai ned sections from experimental ERKO hearts had fewer viable myocytes compar ed with controls. Transmission electron microscopy revealed swollen and fra gmented mitochondria with amorphous and granular bodies, loss of matrix, an d rupture of cristae in experimental ERKO hearts. This is the first demonst ration that estrogen receptor-a plays a cardioprotective role in ischemia-r eperfusion injury in males.