Key result
Tamoxifen cuts spontaneous beating frequency ~80% in neonatal rat cardiomyocytes and isolated perfused hearts.
Why the study?
Tamoxifen is widely prescribed for breast cancer, but its inotropic and chronotropic effects needed evaluation.
Does tamoxifen alter the inotropic and chronotropic contractile activity in primary neonatal cardiomyocytes and isolated perfused hearts?
Does tamoxifen alter the inotropic and chronotropic contractile activity in primary neonatal cardiomyocytes and isolated perfused hearts?
Absolute Event Rate: 3.6% vs 17.8%
p-value: p=<0.05
Tamoxifen exerts a strong negative chronotropic effect without altering inotropy in isolated rat hearts and cardiomyocytes, likely mediated by VSOR/VRAC channel inhibition, which may explain some of its clinical arrhythmogenic potential.
May account for tamoxifen's clinical arrhythmogenic potential; supports VSOR/VRAC inhibition as mediating mechanism.
Tamoxifen, a non-steroidal triphenylethylene antiestrogen, is a widely prescribed drug for treating and preventing estrogen receptor-positive breast cancer. The aim of this study was to evaluate the inotropic and chronotropic effects of tamoxifen on primary cultured neonatal cardiomyocytes and isolated adult Langendorff-perfused hearts. Osmotic swelling of primary cultured neonatal cardiomyocytes activated large anionic currents with the biophysical phenotype of the volume-sensitive outwardly rectifying (VSOR) chloride channel (also known as VRAC, volume-regulated anion channel). Tamoxifen at 10 µM suppressed VSOR/VRAC by ~ 84–85% in a voltage-independent manner. The same maneuver nearly stopped the spontaneous beating of the cardiomyocytes with no change in the contraction amplitude. In isolated Langendorff-perfused hearts, tamoxifen produced a significant negative chronotropic effect, as evidenced by a decrease in heart rate. No significant inotropic effect was observed, as there were no detectable changes in left ventricular systolic pressure, left ventricular developed pressure, and left ventricular end-diastolic pressure. At the single contraction level, administration of 10 µM tamoxifen resulted in broadening of the contraction amplitude histogram and a significant shift of the peak-to-peak interval histogram towards more prolonged values with signs of ectopic events.
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Maksimcheva et al. (2026) studied Healthy (Animal Model) (n=10). Tamoxifen vs. Baseline (Control) was evaluated on Contraction frequency of spontaneous cell beating (beats/min) (p=<0.05). Tamoxifen at 10 µM reduced the spontaneous beating frequency of neonatal rat cardiomyocytes by approximately 80% and produced a significant negative chronotropic effect in isolated perfused hearts.
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