Linear heart rate variability (HRV) indices are dependent on the mean heart rate, which has been demonstrated in different models (from sinoatrial cells to humans). The association between nonlinear HRV indices, including those provided by recurrence plot quantitative analysis (RQA), and the mean heart rate (or the mean cardiac period, also called meanNN) has been scarcely studied. For this purpose, we analyzed RQA indices of five minute-long HRV time series obtained in the supine position and during active standing from 30 healthy subjects and 29 end-stage renal disease (ESRD) patients (before and after hemodialysis). In the supine position, ESRD patients showed shorter meanNN (i.e., faster heart rate) and decreased variability compared to healthy subjects. The healthy subjects responded to active standing by shortening the meanNN and decreasing HRV indices to reach similar values of ESRD patients. Bivariate correlations between all RQA indices and meanNN were significant in healthy subjects and ESRD after hemodialysis and for most RQA indices in ESRD patients before hemodialysis. Multiple linear regression analyses showed that RQA indices were also dependent on the position and the ESRD condition. Then, future studies should consider the association among RQA indices, meanNN, and these other factors for a correct interpretation of HRV.

The inter beat interval (IBI) duration and systolic blood pressure (SBP) are cardiovascular variables related through several feedback mechanisms. We propose the analysis of diagonal lines in cross recurrence plots (CRPs) from IBI and SBP embedded within the same phase space to identify events where trajectories of both variables concur. The aim of the study was to describe the relationship between IBI and SBP of healthy subjects using CRP and diagonal analysis during baseline condition—supine position (SP)—and how the relationship changes during the physiological stress of active standing (AS). IBI and SBP time series were obtained from continuous blood pressure recordings during SP and AS (15 min each) in 19 young healthy subjects. IBI and SBP time series were embedded within a five-dimensional phase space using an embedding delay estimated from cross correlation between IBI and SBP. During SP, mean CRP showed high determinism (≥85%) and also brief but repeated events where both variables stay within a reduced space. Most quantitative recurrences analysis indexes of CRP increased significantly (p < 0.05) during AS. CRP analysis showed short diagonals indicating a very strong deterministic relationship between IBI and SBP with intermittent unlocking periods. The strength of IBI and SBP relationship increased during the physiological stress of AS. The CRP method allowed a rigorous quantitative description of the deterministic association between these two variables. Diagonal lines were intermittent and not always parallel, showing that there is not a defined and unique rhythm. This suggests the activation of different influences at different times and with different precedence between the heart rate and blood pressure in response to AS.

The scaling properties of heart rate variability data are reliable dynamical features to predict mortality and for the assessment of cardiovascular risk. The aim of this manuscript was to determine if the scaling properties, as provided by the sign and magnitude analysis, can be used to differentiate between pathological changes and those adaptations basically introduced by modifications of the mean heart rate in distinct manoeuvres (active standing or hemodialysis treatment, HD), as well as clinical conditions (end stage renal disease, ESRD). We found that in response to active standing, the short-term scaling index (α₁) increased in healthy subjects and in ESRD patients only after HD. The sign short-term scaling exponent (α_1sign) increased in healthy subjects and ESRD patients, showing a less anticorrelated behavior in active standing. Both α₁ and α_1sign did show covariance with the mean heart rate in healthy subjects, while in ESRD patients, this covariance was observed only after HD. A reliable estimation of the magnitude short-term scaling exponent (α_1magn) required the analysis of time series with a large number of samples (>3000 data points). This exponent was similar for both groups and conditions and did not show covariance with the mean heart rate. A surrogate analysis confirmed the presence of multifractal properties (α_1magn > 0.5) in the time series of healthy subjects and ESDR patients. In conclusion, α₁ and α_1sign provided insights into the physiological adaptations during active standing, which revealed a transitory impairment before HD in ESRD patients. The presence of multifractal properties indicated that a reduced short-term variability does not necessarily imply a declined regulatory complexity in these patients.

Several heart rate variability (HRV) characteristics of patients with myocardial ischemia are associated with a higher mortality risk. However, the immediate effect of acute ischemia on the HRV nonlinear dynamical behavior is unknown. The objective of this work is to explore the presence of nonlinearity through surrogate data testing and describe the dynamical behavior of HRV in acutely induced ischemia by percutaneous transluminal coronary angioplasty (PTCA) with linear and recurrence quantification analysis (RQA). Short-term electrocardiographic recordings from 68 patients before and after being treated with elective PTCA were selected from a publicly available database. The presence of nonlinear behavior was confirmed by determinism and laminarity in a relevant proportion of HRV time series, in up to 29.4% during baseline conditions and 30.9% after PTCA without statistical difference between these scenarios. After PTCA, the mean value and standard deviation of HRV time series decreased, while determinism and laminarity values increased. Here, the diminishment in overall variability caused by PTCA is not accompanied by a change in nonlinearity detection. Therefore, the presence of nonlinear behavior in HRV time series is not necessarily in agreement with the change of traditional and RQA measures.

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’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.