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Short-Term Estrogen Reduces Myocardial Infarct Size in Oophororectomized Female Rabbits in a Dose-Dependent Manner

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Abstract

17β-estradiol, administered acutely, protects ischemic myocardium in male rabbits. In the present study we investigated the effect of short-term estrogen on myocardial infarct size in oophorectomized female rabbits. We oophorectomized 24 sexually mature New Zealand white female rabbits. Twelve animals were left untreated and 12 received oral conjugated estrogens, 0.15 mg/day, for 4 weeks. At a second stage, a third group of 12 oopherectomized female rabbits was treated with intramuscular conjugated estrogens, 1 mg/day, also for 4 weeks. All rabbits underwent 30 minutes of coronary artery occlusion and 2 hours of reperfusion while on anesthesia with IV pentobarbital. Infarct and risk area were delineated by Zn-Cd fluorescent particles and tetrazolium chloride staining. The infarct size was expressed as a percentage of the risk zone (I/R %). Data are reported on 26 animals that survived the treatment period and the experiment. Heart rate, systolic, and mean blood pressure and double product did not differ between the three groups at baseline, ischemia, and reperfusion. The infarct size of the risk zone was significantly smaller in the intramuscular group compared with both the oral and the placebo group (18.5 ± 3.5% vs. 41.3 ± 9.2% and 43 ± 8.4%, respectively, P = 0.03). Conjugated estrogens, administered intramuscularly at a high dose, protect ischemic myocardium in oophorectomized female rabbits.

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References

  1. Stampfer MJ, Colditz GA, Willett WC, et al. The risk of myocardial infarction associated with the combined use of estrogens and progestins in postmenopausal women. Arch Intern Med 1994;154:1333-1339.

    Google Scholar 

  2. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 1992;117:1016-1037.

    Google Scholar 

  3. Psaty BM, Heckbert SR, Atkins D, et al. The risk of myocardial infarction associated with the combined use of estrogens and progestins in postmenopausal women. Arch Intern Med 1994;154:1333-1339

    Google Scholar 

  4. Barrett-Connor E, Bush TL. Estrogen and coronary heart disease in women. Circulation 1991;265°61-1867.

  5. Sullivan JM. Estrogen replacement. Circulation 1996;94: 2699-2702.

    Google Scholar 

  6. Williams JK, Adams MR, Herrington DM, Clarkson TB. Short-term administration of estrogen and vascular responses of atherosclerotic coronary arteries. J Am Coll Cardiol 1992;20:452-457.

    Google Scholar 

  7. Williams JK, Adams MR, Klopfenstein SH. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation 1990;81:1680-1687.

    Google Scholar 

  8. Williams JK, Honore EK, Washburn SA, Clarkson TB. Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomologous monkeys. J Am Coll Cardiol 1994;24:1757-1761.

    Google Scholar 

  9. Jiang C, Poole-Wilson PA, Sarrel PM, Mochizuki S, Collins P, Macleod KT. Endothelium-independent relaxation of rabbit coronary artery by 17β-oestradiol in vitro. Br J Pharmacol 1991;106:1033-1037.

    Google Scholar 

  10. Sudhir K, Chou TM, Mullen WI, et al. Mechanisms of estrogen-induced vasodilation: In vivo studies in canine coronary conductance and resistance arteries. J Am Coll Cardiol 1995;26:807-814.

    Google Scholar 

  11. Rusko J, Li L, Van Breemer C. 17β-estradiol stimulation of endothelial K+ channels. Biochem Biophys Res Commun 1995;214:367-372

    Google Scholar 

  12. Sarrel PM. Ovarian hormones and the circulation. Maturitas 1990;12:287-298.

    Google Scholar 

  13. Schunkert H, Danser J, Hense HW, Derkx FHM, Kurzinger S, Riegger GAJ. Effects of estrogen replacement therapy on the renin-angiotensin system in postmenopausal women. Circulation 1997;95:39-45.

    Google Scholar 

  14. Keaney JF, Shwaery GT, Xu A, et al. 17β-estradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine. Circulation 1994;89:2251-2259.

    Google Scholar 

  15. Sack MN, Rader DJ, Cannon RO. Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women. Lancet 1994;343:269-270.

    Google Scholar 

  16. Rosseli M, Imthurn B, Keller PJ, Jackson EK, Dubey RK. Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17β-estradiol and norethisterone acetate: A two year follow-up study. Hypertension 1995;25:848-853.

    Google Scholar 

  17. Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S. Induction of calcium-dependent nitric oxide synthesis by sex hormones. Proc Natl Acad Sci USA 1994; 94:5212-5216.

    Google Scholar 

  18. Ylihorhala O, Orpana A, Puolakka J, Pyorala T, Viinikka L. Postmenopausal hormonal replacement decreases plasma levels of endothelin-1. J Clin Endocrinol Metab 1995;80: 3384-3387

    Google Scholar 

  19. Hale SI, Birnbaum Y, Kloner RA. β-Estradiol, but not α-estradiol, reduces myocardial necrosis in rabbits after ischemia and reperfusion. Am Heart J 1996;132:258-262.

    Google Scholar 

  20. Node K, Kitakaze M, Kosaka H, Minamino T, Funaya H, Hori M. Amelioration of ischemia and reperfusion-induced myocardial injury by 17β-estradiol. Circulation 1997;96: 1953-1963

    Google Scholar 

  21. Chen SJ, Li H, Durand J, Oparil S, Chen YF. Estrogen reduces myointimal proliferation after balloon injury of rat carotid artery. Circulation 1996;93:577-584.

    Google Scholar 

  22. Levine RI, Chen SJ, Durand J, Chen YF, Oparil S. Medroxyprogesterone attenuates estrogen-mediated inhibition of neointima formation after balloon injury of the rat carotid artery. Circulation 1996;94:2221-2227.

    Google Scholar 

  23. Wellman GC, Bonev AD, Nelson MT, Brayden JE. Gender differences in coronary artery diameter involve estrogen, nitric oxide, and Ca2+-dependent K+ channels. Circ Res 1996;79:1024-1030.

    Google Scholar 

  24. Kim YD, Chen B, Beauregard J, et al. 17β-estradiol prevents dysfunction of canine coronary endothelium and myocardium and reperfusion arrhythmias after brief ischemia/reperfusion. Circulation 1996;94:2901-2908.

    Google Scholar 

  25. McHugh NA, Cook SM, Schairer JL, Merill GF. Ischemia-and reperfusion-induced ventricular arrhythmias in dogs: Effects of estrogen. Am J Physiol 1995;268:H2569-H2573.

    Google Scholar 

  26. Martin LG, Brenner GM, Jarolim KL, Banschbach MW, Coons DL, Wolfe AK. Effects of sex steroids on myocardial anoxic resistance. Proc Soc Exp Biol Med 1993;202: 288-294.

    Google Scholar 

  27. Magness RR, Rosenfeld CR. Local and systemic estradiol-17β: Effects on uterine and systemic vasodilation. Am J Physiol 1989;256:E536-E542.

    Google Scholar 

  28. Hart MV. Hosepud JD, Hohimer RA, Morton MJ. Hemodynamics during pregnancy and sex steroid administration in guinea pigs. Am J Physiol 1985;249:R179-R185.

    Google Scholar 

  29. Lefer AM. Attenuation of myocardial ischemia-reperfusion injury with nitric oxide replacement therapy. Ann Thorac Surg 1995;60:847-851.

    Google Scholar 

  30. Kloner RA, Braunwald E. Effects of calcium antagonists on infarcting myocardium. Am J Cardiol 1987;59:84B-94B.

    Google Scholar 

  31. Gisclard V, Flavahan NA, Vanhoutte PM. Alpha adrenergic responses of blood vessels of rabbits after ovariectomy and administration of 17β-estradiol. J Pharmacol Exp Ther 1987;240:466-470.

    Google Scholar 

  32. Hearse DJ, Yellon DM, Downey JM. Can beta blockers limit myocardial infarct size? Eur Heart J 1986;7:925-930.

    Google Scholar 

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Authors and Affiliations

  1. Second Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece

    Eftihia Sbarouni, Efstathios K. Iliodromitis, Elias Bofilis, Zenon S. Kyriakides & Dimitrios Th. Kremastinos

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  1. Eftihia Sbarouni
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  2. Efstathios K. Iliodromitis
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  3. Elias Bofilis
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  4. Zenon S. Kyriakides
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  5. Dimitrios Th. Kremastinos
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Sbarouni, E., Iliodromitis, E.K., Bofilis, E. et al. Short-Term Estrogen Reduces Myocardial Infarct Size in Oophororectomized Female Rabbits in a Dose-Dependent Manner. Cardiovasc Drugs Ther 12, 457–462 (1998). https://doi.org/10.1023/A:1007750015372

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