Protective action of 17beta-estradiol in cardiac cells: implications for hyperkalemic cardioplegia.
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 17beta-estradiol may possess protective properties in the ischemic myocardium. The purpose of the present study was to examine the action of 17beta-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 17beta-estradiol.


RESULTS
In control cardiomyocytes, the cytosolic concentration of Ca2+ was 138+/-11 nmol/L and cell length 93+/-11 microm. Exposure to high K+ (+16 mmol/L KCl) significantly increased cytosolic Ca2+ to 2,191+/-87 nmol/L (p < 0.001), and produced cell shortening (length at 39+/-5 microm; p < 0.001). 17beta-Estradiol (10 micromol/L) acutely prevented high K+ to induce either intracellular Ca2+ loading (144+/-13 nmol/L, p < 0.001) or hypercontracture (91+/-10 microm, p < 0.001). Tamoxifen (10 micromol/L), an antiestrogen, abolished the protective effect of 17beta-estradiol.


CONCLUSIONS
We conclude that 17beta-estradiol prevents hyperkalemia-induced Ca2+ loading and hypercontracture through a direct and tamoxifen-sensitive action in cardiomyocytes. This study raises the possibility that 17beta-estradiol should be considered as a cardioprotective adjunct toward a safer hyperkalemic cardioplegia.
Jovanović
S
S
Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Jovanović
A
A
Shen
W K
WK
Terzic
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced; D006352:Heart Ventricles / Q000166:cytology; D009206:Myocardium / Q000166:cytology*; D011188:Potassium / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D013629:Tamoxifen; D004958:Estradiol; D011188:Potassium; D002118:Calcium