Abstract 316: Influence of Aging and Na Channels on Sinus Rhythm and Heart Rate Variability

Heart rate variability (HRV) is an index of cardiovascular health and reflects the ability of the heart to adjust sinus rhythm in response to autonomic regulation, a process affected by age. Importantly, Na channels have emerged as key components of discharge and conduction of the sino-atrial node, but whether altered Na channels affect HRV remains to be established. Thus, we studied effects of aging and altered Na channels on heart rate and HRV using wild type (WT) mice and mice with phosphomimetic mutation of Na channel Nav1.5 at Ser571 (S571E mice). Electrocardiograms (ECG) were obtained in male conscious mice at ~4, ~12, ~18, and ~24 months of age (n=13-51). The mean RR interval of the ECG was similar in WT mice at ~4, ~12, and ~18 months (83±4, 81±2, 83±2 ms, respectively), but increased at ~24 months (85±5 ms). In contrast, mean RR interval in S571E mice was maximal at ~4 months (86±6 ms) and progressively decreased at ~12 (83±9 ms), ~18 (79±2 ms), and ~24 months (80±3 ms). Standard deviation of RR intervals (SDRR), an indicator of RR variability, was maximal in WT at ~4 months (3.8±1.6 ms) and was reduced at ~12, ~18, and ~24 months (2.1±0.9, 2.4±1, and 2.6±1.2 ms). Similarly, SDRR was maximal in S571 at ~4 (5.1±2.6 ms) and ~12 months (4.3±1.5 ms), and decreased at ~18 and ~24 months of age (2.6±1.0 and 3.1±1.1 ms). Standard deviation of instantaneous (SD1) and long-term (SD2) RR interval variability, indicative of parasympathetic and sympathetic influence, respectively, were derived from Poincaré plots of RR i and RR i+1 intervals. Overall, SD1 was preserved for the two groups of aging mice, whereas SD2 was maximal at ~4 months and decreased at ~18 and ~24 months. In the presence of complete autonomic block (propranolol and atropine), RR interval increased in young (~4 months, +10%) and old (~24 months, +16%) WT mice. Similarly, autonomic block increased RR interval in young (~4 months, +12%) and old (~24 months, +14%) S571E, but it abrogated RR interval differences between young and old. For the two genotypes, autonomic block reduced SDRR and SD2 exclusively in young animals, abolishing age-related differences in HRV. Overall, these data suggest that Na + channel function conditions heart rate and its age-related adaptations, but does not interfere with the decline of HRV occurring with age.