A Novel Quantitative Electrocardiography Strategy Reveals the Electroinhibitory Effect of Tamoxifen on the Mouse Heart.

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.

Influence of 2nd-degree AV blocks, ECG recording length, and recording time on heart rate variability analyses in horses.

OBJECTIVES: To assess the influence of 2nd-degree AV blocks (AVB) on RR interval-based heart rate variability (HRV) variables; to investigate the effect of using PP interval time series and of artifact filtering on HRV analyses; to investigate the influence of electrocardiogram (ECG) recording length and time of recording; and to calculate day-to-day variability and reference intervals of HRV variables. ANIMALS: Thirty healthy adult horses. METHODS: RR and PP interval time series were extracted from 10-h Holter ECGs and an automated filter was applied to the RR time series (RRf). Time-domain HRV variables were calculated based on RR, PP, and RRf time series and their relation to the number of AVBs was assessed. Hourly 10- and 60-min segments were extracted to investigate the influence of segment length and recording time on HRV variables. Day-to-day variability and reference intervals of HRV variables were calculated. RESULTS: Variables of short-term HRV were significantly influenced by the number of AVBs when based on RR, but not when based on PP- and RRf time series. PP- and RRf-based HRV variables were in good agreement. The majority of HRV variables were influenced by recording time and ECG segment length. Day-to-day variability of HRV variables was low when based on 10-h ECG recordings but moderate to high when based on 60-min and 10-min recordings. CONCLUSIONS: Second-degree AVBs significantly influence conventional RR-based, but not PP- and RRf-based time-domain HRV variables. However, PP and RRf analyses have limitations and recording length and time of recording must be considered.