Department of Physiology, New York Medical College, Valhalla, New York.
IHU Liryc, Electrophysiology and Heart Modeling Institute, Bordeaux University Foundation, F-33600 Pessac-Bordeaux, France, with Univ. Bordeaux and INSERM, CRCTB, U1045, Bordeaux, France.
Am J Physiol Heart Circ Physiol. 2020 Oct 1;319(4):H893-H905. doi: 10.1152/ajpheart.00379.2020. Epub 2020 Sep 4.
Heart rate variability (HRV) is a measure of variation in time interval between heartbeats and reflects the influence of autonomic nervous system and circulating/locally released factors on sinoatrial node discharge. Here, we tested whether electrocardiograms (ECGs) obtained in conscious, restrained mice, a condition that affects sympathovagal balance, reveal alterations of heart rhythm dynamics with aging. Moreover, based on emergence of sodium channels as modulators of pacemaker activity, we addressed consequences of altered sodium channels on heart rhythm. C57Bl/6 mice and mice with enhanced late sodium current due to Nav1.5 mutation at Ser571 (S571E) at ~4 to ~24 mo of age, were studied. HRV was assessed using time- and frequency-domain and nonlinear parameters. For C57Bl/6 and S571E mice, standard deviation of RR intervals (SDRR), total power of RR interval variation, and nonlinear standard deviation 2 (SD2) were maximal at ~4 mo and decreased at ~18 and ~24 mo, together with attenuation of indexes of sympathovagal balance. Modulation of sympathetic and/or parasympathetic divisions revealed attenuation of autonomic tone at ~24 mo. At ~4 mo, S571E mice presented lower heart rate and higher SDRR, total power, and SD2 with respect to C57Bl/6, properties reversed by late sodium current inhibition. At ~24 mo, heart rate decreased in C57Bl/6 but increased in S571E, a condition preserved after autonomic blockade. Collectively, our data indicate that aging is associated with reduced HRV. Moreover, sodium channel function conditions heart rate and its age-related adaptations, but does not interfere with HRV decline occurring with age. We have investigated age-associated alterations of heart rate properties in mice using conscious electrocardiographic recordings. Our findings support the notion that aging is coupled with altered sympathovagal balance with consequences on heart rate variability. Moreover, by using a genetically engineered mouse line, we provide evidence that sodium channels modulate heart rate and its age-related adaptations.
心率变异性（HRV）是衡量心跳时间间隔变化的一种方法，反映了自主神经系统和循环/局部释放因子对窦房结放电的影响。在这里，我们测试了在清醒、受限制的小鼠中获得的心电图（ECG），这种情况会影响交感神经和迷走神经的平衡，是否揭示了随年龄增长而出现的心律动力学变化。此外，基于钠离子通道作为起搏器活动调节剂的出现，我们研究了改变钠离子通道对心律的影响。我们研究了 C57Bl/6 小鼠和由于 Nav1.5 突变导致 Ser571（S571E）处晚期钠离子电流增强的小鼠，这些突变发生在 4 至 24 个月龄。使用时间和频率域以及非线性参数评估 HRV。对于 C57Bl/6 和 S571E 小鼠，RR 间隔标准差（SDRR）、RR 间隔变化总功率和非线性标准差 2（SD2）在 4 个月龄时最大，在 18 个月龄和 24 个月龄时降低，同时交感神经和迷走神经平衡指数减弱。对交感神经和/或副交感神经分支的调制揭示了 24 个月龄时自主神经张力的减弱。在 4 个月龄时，S571E 小鼠的心率较低，SDRR、总功率和 SD2 较高，与 C57Bl/6 相比，这一特性在晚期钠离子电流抑制后逆转。在 24 个月龄时，C57Bl/6 小鼠的心率降低，但 S571E 小鼠的心率升高，在自主神经阻断后保持不变。总之，我们的数据表明，衰老与 HRV 降低有关。此外，钠离子通道功能调节心率及其与年龄相关的适应，但不干扰随年龄增长而发生的 HRV 下降。我们使用清醒状态下的心电图记录研究了与年龄相关的小鼠心率特征的改变。我们的研究结果支持这样一种观点，即衰老与交感神经和迷走神经平衡的改变有关，这对心率变异性有影响。此外，通过使用基因工程小鼠品系，我们提供了证据表明钠离子通道调节心率及其与年龄相关的适应。
