The Role of Autonomic Nervous System and Baroreflex in the Pattern of Heart Rate Fragmentation

Abstract

Although rapid oscillations of the heart rate (HR) are commonly attributed to vagal modulation of the heart, a pattern of ultra‐rapid HR variation has been recently studied. This type of variation, named HR fragmentation (HRF), has been shown to be increased in aging and coronary diseases and seems to be linked to the risk of death and life‐threatening cardiovascular events. However, the mechanisms behind HRF are unknown. Thus, the aim of this study was to evaluate the influence of the autonomic nervous system (ANS) and arterial baroreceptors on HRF. For this, electrodes for electrocardiogram (ECG) and a catheter into femoral vein were implanted in Wistar rats. On the next day, under ECG recordings, the rats were submitted to selective pharmacological blockade of cardiac autonomic receptors with atenolol (4 mg/kg iv in bolus followed by 0.8 mg/kg/h iv) followed by methylatropine (2 mg/kg in bolus followed by 0.4 mg/kg/h iv) or vice‐versa. Another group underwent sinoaortic denervation (SAD), or sham‐operation, and received a catheter in femoral artery. On the next day, SAD and sham rats had its blood pressure directly recorded. All recordings were performed in freely moving animals. Pulse interval or RR‐interval series were generated and transformed into sequence of symbols "−1”, “0” or “1" when the difference between successive values (transitions) was negative, zero, or positive, respectively. In addition, the transitions between symbols "−1" and "1" were classified as "hard" (H) while those between "−1" (or "1") and "0" were classified as "soft" (S). Next, sequences of 4 consecutive symbols were classified according to the number and type of transition, i.e. S, M or H, where M represents mixed transitions (H and S). The total percentage of inflection points (PIP) was also quantified. PIP increased after sympathetic (66±2 to 73±2), parasympathetic (68±1 to 73±1) and double autonomic blockade (67±1 to 73±1). The percentage of sequences with H transitions was lower after parasympathetic (27±3 vs 74±2) and double blockade (43±4 vs 76±1), while sequences with S and M transitions were higher after parasympathetic (S: 28±3 vs 7±1% and M: 44±2 vs 18±1%) and double blockade (S: 15±2 vs 6±1 and M: 41±2 vs 17±1%). The percentage of sequences with M‐type transitions increased after sympathetic blockade (16±1 to 23±3), while no change was found with H and S‐type transitions. PIP was lower in SAD rats (68±2) when compared to the sham counterparts (88±1). Regarding type, the percentage of H transitions was higher in SAD (90±1 vs 20±1), whereas sham rats showed more S (27±1 vs 2±0.1) and M‐type transitions (53±1 vs 7±1). In conclusion, the ANS, specially its parasympathetic branch, attenuates HRF. Moreover, although the removal of arterial baroreceptors represents the loss of an important cardiocirculatory control system, the denervated rats presented lower overall HRF. Nevertheless, the percentage of H‐type transitions is higher in SAD rats, evidencing that both the amount and type of fragmentation represent important indices under physiological and pathophysiological conditions.Support or Funding InformationCNPq, CAPES and FAPESP