Revisiting nonlinearity of heart rate variability in healthy aging

Abstract Aging is commonly regarded as a physiological process in which the dynamic complexity of physiological time series and organ systems is gradually lost. This notion is derived from the identification of a decline of nonlinear measures with the advance of aging. However, additional research on cardiovascular control studied through heart rate variability (HRV), i.e., the instantaneous changes in heart rate, shows that despite the constriction of its statistical distribution, the nonlinear organization remains present in advanced age. Here, we used surrogate data testing to investigate the presence of nonlinear information in HRV time series from a publicly available database of 1121 healthy human subjects from 18 to 92 years old. We also studied the influence of basic clinical features, such as sex, body mass index (BMI), and mean heart rate (HR), on such nonlinear information. We found that the percentage of nonlinear time series after 30 years of age diminishes significantly (p < 0.01). Furthermore, larger BMI and HR are associated with the presence of more linear information in HRV, while the female sex is associated with the manifestation of nonlinear information. This work provides a common background for the contextualized interpretation of nonlinear testing and shows that the nonlinear content of HRV time series diminishes through aging

Recurrence quantitative analysis of heart rate variability during intradialytic hypotension

Recurrence quantitative analysis (RQA) of heart rate variability (HRV) is helpful for the non-invasive study of the regulation of the cardiovascular system by the autonomic nervous system. HRV monitoring during hemodialysis (HD) sessions of end-stage renal disease patients reflects a sympathetic hyperactivity that has been proposed as an early marker of intradialytic hypotension (IDH). However, neither intradialytic HRV analysis nor episodes of IDH have been explored from the RQA perspective. We studied the HRV dynamics with linear and RQA indices during intradialytic recordings (N = 38) in which 39.5% of patients presented IDH. Patients with IDH showed a restricted HRV during the whole HD compared to patients with stable blood pressure (p < 0.05). Although the RQA results during HD were heterogeneous, laminarity and the recurrence time of the second type revealed a constricted behavior around the onset of the IDH episodes. RQA analysis complemented the linear HRV measure to reveal a characteristic behavior immediately before and after the IDH episode. We also explored a framework for IDH prediction with a linear HRV index, the standard deviation of the differences between adjacent heartbeats intervals, which was associated in the early moments of HD with the development of IDH throughout HD sessions (sensitivity 80%, specificity 82.6%). The observed differences between groups may be of clinical utility for an early identification of patients prone to IDH

Cell Culture Platforms with Controllable Stiffness for Chick Embryonic Cardiomyocytes

For several years, cell culture techniques have been physiologically relevant to understand living organisms both structurally and functionally, aiming at preserving as carefully as possible the in vivo integrity and function of the cells. However, when studying cardiac cells, glass or plastic Petri dishes and culture-coated plates lack important cues that do not allow to maintain the desired phenotype, especially for primary cell culture. In this work, we show that microscaffolds made with polydimethylsiloxane (PDMS) enable modulating the stiffness of the surface of the culture substrate and this originates different patterns of adhesion, self-organization, and synchronized or propagated activity in the culture of chick embryonic cardiomyocytes. Thanks to the calcium imaging technique, we found that the substrate stiffness affected cardiomyocyte adhesion, as well as the calcium signal propagation in the formed tissue. The patterns of activity shown by the calcium fluorescence variations are reliable clues of the functional organization achieved by the cell layers. We found that PDMS substrates with a stiffness of 25 kPa did not allow the formation of cell layers and therefore the optimal propagation of the intracellular calcium signals, while softer PDMS substrates with Young&#8217;s modulus within the physiological in vivo reported range did permit synchronized and coordinated contractility and intracellular calcium activity. This type of methodology allows us to study phenomena such as arrhythmias. For example, the occurrence of synchronized activity or rotors that can initiate or maintain cardiac arrhythmias can be reproduced on different substrates for study, so that replacement tissues or patches can be better designed

In Vitro Modulation of Spontaneous Activity in Embryonic Cardiomyocytes Cultured on Poly(vinyl alcohol)/Bioglass Type 58S Electrospun Scaffolds

Because of the physiological and cardiac changes associated with cardiovascular disease, tissue engineering can potentially restore the biological functions of cardiac tissue through the fabrication of scaffolds. In the present study, hybrid nanofiber scaffolds of poly (vinyl alcohol) (PVA) and bioglass type 58S (58SiO2-33CaO-9P2O5, Bg) were fabricated, and their effect on the spontaneous activity of chick embryonic cardiomyocytes in vitro was determined. PVA/Bg nanofibers were produced by electrospinning and stabilized by chemical crosslinking with glutaraldehyde. The electrospun scaffolds were analyzed to determine their chemical structure, morphology, and thermal transitions. The crosslinked scaffolds were more stable to degradation in water. A Bg concentration of 25% in the hybrid scaffolds improved thermal stability and decreased degradation in water after PVA crosslinking. Cardiomyocytes showed increased adhesion and contractility in cells seeded on hybrid scaffolds with higher Bg concentrations. In addition, the effect of Ca2+ ions released from the bioglass on the contraction patterns of cultured cardiomyocytes was investigated. The results suggest that the scaffolds with 25% Bg led to a uniform beating frequency that resulted in synchronous contraction patterns

Baroreflex Sensitivity Assessment Using the Sequence Method with Delayed Signals in End-Stage Renal Disease Patients

Impaired baroreflex sensitivity (BRS) is partially responsible for erratic blood pressure fluctuations in End-Stage Renal Disease (ESRD) patients on chronic hemodialysis (HD), which is related to autonomic nervous dysfunction. The sequence method with delayed signals allows for the measurement of BRS in a non-invasive fashion and the investigation of alterations in this physiological feedback system that maintains BP within healthy limits. Our objective was to evaluate the modified delayed signals in the sequence method for BRS assessment in ESRD patients without pharmacological antihypertensive treatment and compare them with those of healthy subjects. We recruited 22 healthy volunteers and 18 patients with ESRD. We recorded continuous BP to obtain a 15-min time series of systolic blood pressure and interbeat intervals during the supine position (SP) and active standing (AS) position. The time series with delays from 0 to 5 heartbeats were used to calculate the BRS, number of data points, number of sequences, and estimation error. The BRS from the ESRD patients was smaller than in healthy subjects (p < 0.05). The BRS estimation with the delayed sequences also increased the number of data points and sequences and decreased the estimation error compared to the original time series. The modified sequence method with delayed signals may be useful for the measurement of baroreflex sensitivity in ESRD patients with a shorter recording time and maintaining an estimation error below 0.01 in both the supine and active standing positions. With this framework, it was corroborated that baroreflex sensitivity in ESRD is decreased when compared with healthy subjects

Recurrence plot analysis of heart rate variability in end-stage renal disease treated twice-weekly by hemodialysis with or without intradialytic hypotension

Recurrence quantitative analysis (RQA) indices of heart rate variability (HRV) have shown a different adjustment in the sympathetic-driven dynamical response to active standing (AS) and hemodialysis (HD), characterized by increased laminar states in HRV. AS test is a maneuver in which subjects actively change their body posture from supine position (SP) to AS. In end-stage renal disease (ESRD) patients treated twice-weekly by HD, we found reduced changes in RQA indices to AS before HD that are partially recovered after treatment; laminarity, trapping time and recurrence time of the second type values were significantly lower in SP than during AS ($$p<0.05$$). Patients who developed intradialytic hypotension (IDH) did not show a significant response to AS in contrast with patients who did not develop IDH. Also, the mean duration of heartbeat intervals significantly influenced RQA indices ($$p<0.05$$), and this correlation depended on the observation moment (before or after HD). These findings suggest that the cardiac response to the autonomic modulation measured by RQA is different in IDH patients even before HD. Furthermore, the influence of the mean heart rate changes seems to play an important role in the short-term control of HRV behavior in ESRD