A custom analysis of R-R interval properties reveals alterations in the brain-heart axis in experimental animals with metabolic syndrome.

Background: Metabolic syndrome (MetS) is a cluster of conditions that increases the risk of cardiovascular complications and all-cause mortality. MetS manifests reduced heart rate variability, but factors underlying the process remain to be fully elucidated. Objective: To gain new insights into the effects of MetS on heart rhythm dynamics, we developed a custom algorithm to analyze the distribution and span of R-R intervals. Methods: MetS was induced in male and female mice by Western diet feeding (WD mice), whereas animals on regular chow were used as controls (Ctrl mice). The sequence of R-R intervals of electrocardiograms and their deviation were sorted and normalized using an approximation of the distribution function to obtain sequences of the R-R interval duration (sortRR) and the R-R interval deviation (sortRRdev). Results: sortRR sequences revealed shorter intervals in WD mice than in Ctrl mice within the range of intermediate and long R-R intervals, indicating that mice with MetS have limited capability to lower heart rate. Moreover, sortRRdev sequences had smaller amplitudes for WD mice, consistent with reduced heart rate variability. Inhibition of sympathetic inputs abrogated differences in sortRR sequences for the 2 groups of mice, whereas inhibition of parasympathetic inputs suppressed differences in the sortRRdev series. Interestingly, Western diet feeding in animals lacking β-adrenergic receptors minimally affected heart rate dynamics in female mice, but revealed significant alterations in male animals, which were abrogated by parasympathetic inhibition. Conclusion: These results support the notion that sympathoexcitation and parasympathetic withdrawal occur with MetS and affect the duration, functional range, and variability of R-R intervals.