Fractal-Like Behavior of the Heart-Beat Intervals is Encoded within Intrinsic Complexity of Pacemaker Cells Residing in the Sinoatrial Node and Modulated by Autonomic Input to the Heart

The heart rate and rhythm are controlled by complex chaotic neural, chemical and hormonal networks which are not strictly regular, but exhibit fluctuations across multiple-time scales. Therefore, it is not surprising that decoding of the ECG in mammals, even under resting conditions, reveals scale-invariant dynamics and beat-interval variability (BIV). Moreover, fractal-like behavior of heart beat intervals, which reveals itself in a power-law dependence of the frequency distribution of its intrinsic regimes, contributes to the complexity of the mammalian heart's rhythm. The traditional explanation for BIV and fractal-like behavior of heart beat intervals is that this result from the balance of sympathetic and parasympathetic autonomic input to the heart. But whether the sinoatrial node (SAN), the heart's primary pacemaker, or pacemaker cells isolated from the SAN exhibit fractal-like behavior of beating intervals in the absence of autonomic input is unknown.We analyzed beating rhythms: (i) in vivo, when the brain input to the SAN is intact; ii) during autonomic denervation in vivo; iii) in intact isolated (denervated) SAN; and iv) in single pacemaker cells isolated from the SAN. By segregating each component of the brain-pacemaker cascade, we discovered that fractal-like beating interval exhibit in SAN tissue and although the beat interval of single pacemaker cells isolated from the SAN is rhythmic it does not exhibit fractal-like behavior. Therefore, cell-to-cell communication among pacemaker cells within the SAN tissue is required to impart their fractal-like beating interval behavior within the SAN. Autonomic input from the brain to the heart in vivo modulates both the rate and rhythm at which pacemaker cells beat and its fractal-like behavior, but it is not required for isolated SAN fractal-like complexity.