Protective action of 17β-estradiol in cardiac cells: Implications for hyperkalemic cardioplegia

Sofija Jovanović, Aleksandar Jovanović, Win K. Shen, Andre Terzic

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background. Hyperkalemic cardioplegic solutions effectively arrest the heart, but may also induce intracellular Ca2+ loading and cellular hypercontracture, which could contribute to ventricular dysfunction associated with global surgical ischemia. Recently, it has been proposed that 17β-estradiol may possess protective properties in the ischemic myocardium. The purpose of the present study was to examine the action of 17β-estradiol on cardiac cells exposed to hyperkalemic stress. Methods. Single ventricular cardiomyocytes, a preparation devoid of vascular and neuronal elements, were isolated from guinea pig hearts, loaded with a Ca2+-sensitive fluorescent probe, and imaged by digital epifluorescent microscopy. The emitted fluorescence of the probe, a measure of intracellular Ca2+ concentration, and cell length were simultaneously recorded during hyperkalemic challenge, in the absence or presence of 17β-estradiol. Results. In control cardiomyocytes, the cytosolic concentration of Ca2+ was 138 ± 11 nmol/L and cell length 93 ± 11 μm. Exposure to high K+ (+16 mmol/L KCI) significantly increased cytosolic Ca2+ to 2,191 ± 187 nmol/L (p < 0.001), and produced cell shortening (length at 39 ± 5 μm; p < 0.001). 17β- Estradiol (10 μmol/L) acutely prevented high K+ to induce either intracellular Ca2+ loading (144 ± 13 nmol/L, p < 0.001) or hypercontracture (91 ± 10 μm, p < 0.001). Tamoxifen (10 μmol/L), an antiestrogen, abolished the protective effect of 17β-estradiol. Conclusions. We conclude that 17β-estradiol prevents hyperkalemia-induced Ca2+ loading and hypercontracture through a direct and tamoxifen-sensitive action in cardiomyocytes. This study raises the possibility teat 17β-estradiol should be considered as a cardioprotective adjunct toward a safer hyperkalemic cardioplegia.

Original languageEnglish (US)
Pages (from-to)1658-1661
Number of pages4
JournalAnnals of Thoracic Surgery
Volume66
Issue number5
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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