(Circulation. 1997;96:1953-1963.)
© 1997 American Heart Association, Inc.
Articles |
Amelioration of Ischemia- and Reperfusion-Induced Myocardial Injury by 17ß-Estradiol
Role of Nitric Oxide and Calcium-Activated Potassium Channels
From the First Department of Medicine and the First Department of Physiology (H.K.), Osaka University School of Medicine, Osaka, Japan.
Correspondence to Masafumi Kitakaze, MD, PhD, First Department of Medicine, Osaka University School of Medicine, 2-2 Yamadaoka, Suita 565, Japan. E-mail kitakaze{at}medone.med.osaka-u.ac.jp
Background 17ß-Estradiol increases the production of nitric oxide (NO) and prostacyclin and opens Ca2+-activated K+ (KCa) channels. Whether these effects of 17ß-estradiol reduce infarct size and the incidence of ventricular arrhythmia was investigated in dogs subjected to myocardial ischemia and reperfusion.
Methods and Results Infarct size was measured in open-chest dogs after 90 minutes' occlusion of the left anterior descending coronary artery and a subsequent 6 hours of reperfusion. Infusion of 17ß-estradiol into the coronary artery was initiated 10 minutes before coronary occlusion and continued until after 1 hour of reperfusion, with the exception of the occlusion period. The difference in NO concentration between coronary venous and arterial blood 10 minutes after the onset of reperfusion was significantly greater in dogs treated with 17ß-estradiol (10 ng · kg-1 · min-1) than in control animals. Infarct size (13.1±3.0% versus 43.7±5.4% of the area at risk) and the incidence of ventricular arrhythmia during ischemia and reperfusion periods were significantly reduced in the 17ß-estradiol group. Both NG-nitro-L-arginine methyl ester (an inhibitor of NO synthase) and iberiotoxin (a blocker of KCa channels) reduced both the infarct size-limiting effect (infarct size, 29.3±3.0% and 31.7±2.1%, respectively) and the antiarrhythmic effect of 17ß-estradiol; indomethacin (an inhibitor of cyclooxygenase) did not attenuate the beneficial effects of 17ß-estradiol.
Conclusions 17ß-Estradiol reduced both myocardial infarct size and the occurrence of ischemia- and reperfusion-induced ventricular arrhythmias, which appear to be mediated by NO and the opening of KCa channels in canine hearts.
Key Words: myocardial infarction • endothelium-derived factors • ischemia • reperfusion • hormones
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