(Circulation. 1996;94:2901-2908.)
© 1996 American Heart Association, Inc.
Articles |
17ß-Estradiol Prevents Dysfunction of Canine Coronary Endothelium and Myocardium and Reperfusion Arrhythmias After Brief Ischemia/Reperfusion
the Departments of Anesthesia and Physiology and Biophysics, Georgetown University Medical Center, Washington, DC.
Correspondence to Young D. Kim, MD, Department of Anesthesia, Georgetown University Medical Center, 3800 Reservoir Rd NW, Washington, DC 20007.
Background Brief myocardial ischemia is associated with myocardial and coronary endothelial dysfunction caused by oxygen free radicals released during reperfusion. Estrogen, known to have antioxidant activity, may prevent these complications.
Methods and Results We assessed the effect of 2 weeks of treatment with 17ß-estradiol (E, 100 µg·kg-1·d-1, n=12) or placebo (P, n=15) on myocardial and coronary endothelial function during the first 2 hours of reperfusion in dogs subjected to 15 minutes of ischemia induced by occlusion of the left anterior descending coronary artery (LAD). Our results show that the incidence of ventricular arrhythmias significantly decreased in E (3 of 12) compared with P (11 of 15). Systolic shortening, significantly depressed in P during early reperfusion, was maintained at preischemic levels in E. During reperfusion, the increase in LAD flow to acetylcholine, attenuated in P (60±6%), was preserved in E (151±28%) and was associated with increased serum nitrite/nitrate concentration. n-Pentane in exhaled gas in vivo, an index of lipid peroxidation, increased significantly during early reperfusion in P (from 9.1±1.9 to 41.6±13.0 ppb, P<.05) but not in E (23.0±6.9 ppb). In vitro, arterial segments from E generated significantly less superoxide anion after hypoxia/reoxygenation than those from P. Ischemic/reperfused LAD segments from E also revealed a better preservation of endothelium-dependent relaxation in vitro (maximum relaxation, 42±4% versus 24±4% in P; P<.05).
Conclusions Estrogen protects against endothelial and myocardial dysfunction resulting from brief ischemia/reperfusion. This protection may relate to an antioxidant effect of estrogen.
Key Words: hormones • ischemia • reperfusion • endothelium
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