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Protective action of 17beta-estradiol in cardiac cells: implications for hyperkalemic cardioplegia
S Jovanović1, A Jovanović, W K Shen
1Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Insights
17beta-estradiol protects cardiac cells from hyperkalemia-induced damage by preventing calcium overload and hypercontracture. This finding suggests its potential as a cardioprotective agent in heart surgery.
Area of Science:
- Cardiology
- Cell Biology
- Pharmacology
Background:
- Hyperkalemic cardioplegia can cause intracellular calcium overload and hypercontracture, potentially leading to ventricular dysfunction during cardiac surgery.
- 17beta-estradiol has shown promise in protecting ischemic heart tissue.
Purpose of the Study:
- To investigate the protective effects of 17beta-estradiol on cardiac cells subjected to hyperkalemic stress.
Main Methods:
- Isolated guinea pig ventricular cardiomyocytes were loaded with a calcium-sensitive fluorescent probe.
- Intracellular calcium concentration and cell length were measured using digital epifluorescent microscopy during hyperkalemic challenge, with and without 17beta-estradiol.
Main Results:
- High potassium levels significantly increased intracellular calcium and caused cell shortening.
- 17beta-estradiol (10 micromol/L) effectively prevented both calcium loading and hypercontracture.
- Tamoxifen, an antiestrogen, negated the protective effects of 17beta-estradiol.
Conclusions:
- 17beta-estradiol exerts a direct, tamoxifen-sensitive protective effect against hyperkalemia-induced calcium overload and hypercontracture in cardiomyocytes.
- 17beta-estradiol may serve as a valuable cardioprotective adjunct for safer 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.