TY - JOUR
T1 - Protective action of 17β-estradiol in cardiac cells
T2 - Implications for hyperkalemic cardioplegia
AU - Jovanović, Sofija
AU - Jovanović, Aleksandar
AU - Shen, Win K.
AU - Terzic, Andre
N1 - Funding Information:
This research was supported by a Merck Sharp & Dohme International Award in Clinical Pharmacology to Aleksandar Jovanovic and grants from the American Heart Association, the Miami Heart Research Institute, the Bruce and Ruth Rappaport Program in Vascular Biology and Gene Delivery, and the John Tainsh Heart Research Fund to Andre Terzic.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
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U2 - 10.1016/S0003-4975(98)00893-5
DO - 10.1016/S0003-4975(98)00893-5
M3 - Article
C2 - 9875767
AN - SCOPUS:0032217045
SN - 0003-4975
VL - 66
SP - 1658
EP - 1661
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 5
ER -