Department of Cardiac Surgery, School of Medicine, South China University of Technology, Guangzhou, 510006, Guangdong, China.
Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510100, Guangdong, China.
J Cardiovasc Transl Res. 2023 Oct;16(5):1232-1248. doi: 10.1007/s12265-023-10395-5. Epub 2023 May 8.
Tamoxifen, a selective estrogen receptor modulator, was initially used to treat cancer in women and more recently to induce conditional gene editing in rodent hearts. However, little is known about the baseline biological effects of tamoxifen on the myocardium. In order to clarify the short-term effects of tamoxifen on cardiac electrophysiology of myocardium, we applied a single-chest-lead quantitative method and analyzed the short-term electrocardiographic phenotypes induced by tamoxifen in the heart of adult female mice. We found that tamoxifen prolonged the PP interval and caused a decreased heartbeat, and further induced atrioventricular block by gradually prolonging the PR interval. Further correlation analysis suggested that tamoxifen had a synergistic and dose-independent inhibition on the time course of the PP interval and PR interval. This prolongation of the critical time course may represent a tamoxifen-specific ECG excitatory-inhibitory mechanism, leading to a reduction in the number of supraventricular action potentials and thus bradycardia. Segmental reconstructions showed that tamoxifen induced a decrease in the conduction velocity of action potentials throughout the atria and parts of the ventricles, resulting in a flattening of the P wave and R wave. In addition, we detected the previously reported prolongation of the QT interval, which may be due to a prolonged duration of the ventricular repolarizing T wave rather than the depolarizing QRS complex. Our study highlights that tamoxifen can produce patterning alternations in the cardiac conduction system, including the formation of inhibitory electrical signals with reduced conduction velocity, implying its involvement in the regulation of myocardial ion transport and the mediation of arrhythmias. A Novel Quantitative Electrocardiography Strategy Reveals the Electroinhibitory Effect of Tamoxifen on the Mouse Heart（Figure 9）. A working model of tamoxifen producing acute electrical disturbances in the myocardium. SN, sinus node; AVN, atrioventricular node; RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle.
他莫昔芬是一种选择性雌激素受体调节剂，最初用于治疗女性癌症，最近用于诱导啮齿动物心脏的条件性基因编辑。然而，人们对他莫昔芬对心肌的基本生物学影响知之甚少。为了阐明他莫昔芬对心肌心脏电生理的短期影响，我们应用了单导联定量方法，并分析了他莫昔芬在成年雌性小鼠心脏中诱导的短期心电图表型。我们发现他莫昔芬延长了 PP 间期并导致心跳减慢，并通过逐渐延长 PR 间期进一步诱导房室传导阻滞。进一步的相关分析表明，他莫昔芬对 PP 间期和 PR 间期的时间进程具有协同且剂量独立的抑制作用。这种关键时间进程的延长可能代表他莫昔芬特有的心电图兴奋-抑制机制，导致室上性动作电位数量减少，从而导致心动过缓。节段重建显示，他莫昔芬诱导整个心房和部分心室中的动作电位传导速度降低，导致 P 波和 R 波变平。此外，我们检测到先前报道的 QT 间期延长，这可能是由于心室复极 T 波持续时间延长，而不是去极化 QRS 复合体。我们的研究强调，他莫昔芬可以在心脏传导系统中产生图案改变，包括形成具有降低传导速度的抑制性电信号，这表明它参与了心肌离子转运的调节和心律失常的介导。一种新的定量心电图策略揭示了他莫昔芬对小鼠心脏的电抑制作用（图 9）。他莫昔芬在心肌中产生急性电干扰的工作模型。窦房结；房室结；右心房；左心房；右心室；左心室。
