Sedimentology and paleontology of the lower member of the Nogueras Fm (Lower Devonian) at Santa Cruz de Nogueras (Teruel, NE Spain)

An integrated sedimentological and paleontological analysis has been canted out in the lower member (d2a) of the shallow-marine Nogueras Formation (Lower Devonian, Iberian Chains). This formation represents the first carbonate-dominated and fossil-rich sedimentary unit of the Devonian of the Iberian Chains. Nine sedimentary facies, including terrigenous-clastic, mixed and carbonate facies, which are complexly intercalated at bed scale, have been characterized. Based on their sedimentary features and their lateral relationships using Markov chain analysis, two sedimentary models for the lower and upper part of d2a member have been proposed, which represent deposition in a mixed elastic-carbonate shallow marine depositional system. They include terrigenous-clastic intertidal deposits and predominant skeletal, carbonate-dominated and grain-supported facies in the high-energy shallow subtidal zone, whith a clear zonation of the skeletal components (brachiopods, bryozoans and crinoids, from shallow to relatively deep areas). Phosphate nodules, phosphatized fossils, ferruginous crusts and iron ooids, which are frequently associated with the relatively shallower bioclastic brachiopod facies, were probably linked to mineral continental sources and to remobilization in the shallow water high-energy area. The paleontological analysis shows that some of those organisms lived in protected areas of the subtidal zone, including in particular high-diversity communities of brachiopods, adapted to turbid waters with fine terrigenous suspended sediments. Se ha realizado un análisis sedimentológico y paleontológico integrado del miembro inferior (d2a) de la Formación Nogueras, que representa la primera unidad marina somera predominantemente carbonatada del Devónico de las Cadenas Ibéricas. Se han definido nueve facies sedimentarias tcrrígeno-clás ticas, mixtas y carbonatadas, que están complejamente intercaladas a escala de capa, depositadas en un sistema mixto de- trítico-carbonatado de aguas someras. En Junción de sus rasgos sedimentarios y del análisis de sus relaciones laterales mediante cadenas de Markov, se proponen dos modelos sedimentarios para la parte inferior y superior del miembro estudiado. Los dos modelos incluyen depósitos terrígenos en la zona intermareal y facies carbonatadas bioclásticas en la zona submareal somera, con una clara zonación de sus componentes esqueléticos dominantes (braquiópodos, briozoos, crinoides, desde la zona somera a la relativamente profunda). Los nodulos de fosfato, fósiles fósfatizados, costras y ooides ferruginosas frecuentes en las facies bioclasticas de braquiópodos relativamente someras, se relacionaron probablemente con aportes minerales desde el continente y retrabajamiento en la zona marina de alta energía. El análisis paleontológico muestra que algunos de estos organismos vivían en áreas protegidas de la zona submareal, incluyendo particularmente comunidades con alta diversidad de braquiópodos, adaptadas a aguas turbias con elevado sedimento terrígeno fino en suspensión

Melatonin to rescue the aged heart: antiarrhythmic and antioxidant benefits

Aging comes with gradual loss of functions that increase the vulnerability to disease, senescence, and death. The mechanisms underlying these processes are linked to a prolonged imbalance between damage and repair. Damaging mechanisms include oxidative stress, mitochondrial dysfunction, chronodisruption, inflammation, and telomere attrition, as well as genetic and epigenetic alterations. Several endogenous tissue repairing mechanisms also decrease. These alterations associated with aging affect the entire organism. The most devastating manifestations involve the cardiovascular system and may lead to lethal cardiac arrhythmias. Together with structural remodeling, electrophysiological and intercellular communication alterations during aging predispose to arrhythmic events. Despite the knowledge on repairing mechanisms in the cardiovascular system, effective antiaging strategies able to reduce the risk of arrhythmias are still missing. Melatonin is a promising therapeutic candidate due to its pleiotropic actions. This indoleamine regulates chronobiology and endocrine physiology. Of relevance, melatonin is an antiaging, antioxidant, antiapoptotic, antiarrhythmic, immunomodulatory, and antiproliferative molecule. This review focuses on the protective effects of melatonin on age-induced cardiac functional and structural alterations, potentially becoming a new fountain of youth for the heart

A Time-Varying Non-Parametric Methodology for Assessing Changes in QT Variability Unrelated to Heart Rate Variability

OBJECTIVE: To propose and test a novel methodology to measure changes in QT interval variability (QTV) unrelated to RR interval variability (RRV) in non-stationary conditions. METHODS: Time-frequency coherent and residual spectra representing QTV related (QTVrRRV) and unrelated (QTVuRRV) to RRV, respectively, are estimated using time-frequency Cohen's class distributions. The proposed approach decomposes the non-stationary output spectrum of any two-input one-output model with uncorrelated inputs into two spectra representing the information related and unrelated to one of the two inputs, respectively. An algorithm to correct for the bias of the time-frequency coherence function between QTV and RRV is proposed to provide accurate estimates of both QTVuRRV and QTVrRRV. Two simulation studies were conducted to assess the methodology in challenging non-stationary conditions and data recorded during head-up tilt in 16 healthy volunteers were analyzed. RESULTS: In the simulation studies, QTVuRRV changes were tracked with only a minor delay due to the filtering necessary to estimate the non-stationary spectra. The correlation coefficient between theoretical and estimated patterns was >0.92 even for extremely noisy recordings (SNR in QTV =-10dB). During head-up tilt, QTVrRRV explained the largest proportion of QTV, whereas QTVuRRV showed higher relative increase than QTV or QTVrRRV in all spectral bands (P<0.05 for most pairwise comparisons). CONCLUSION: The proposed approach accurately tracks changes in QTVuRRV. Head-up tilt induced a slightly greater increase in QTVuRRV than in QTVrRRV. SIGNIFICANCE: The proposed index QTVuRRV may represent an indirect measure of intrinsic ventricular repolarization variability, a marker of cardiac instability associated with sympathetic ventricular modulation and sudden cardiac death

Quantification of T-wave Morphological Variability Using Time-warping Methods

The aim of this study is to quantify the variation of the T-wave morphology during a 24-hour electrocardiogram (ECG) recording. Two ECG-derived markers are presented to quantify T-wave morphological variability in the temporal, dw, and amplitude, da, domains. Two additional markers, dNLw and dNLa, that only capture the non-linear component of dw and da are also proposed. The proposed markers are used to quantify T-wave time and amplitude variations in 500 24-hour ECG recordings from chronic heart failure patients. Additionally, two mean warped T-waves, used in the calculation of those markers, are proposed to compensate for the rate dependence of the T-wave morphology. Statistical analysis is used to evaluate the correlation between dw, dNLw, da and dNLa and the maximum intra-subject RR range, ΔRR. Results show that the mean warped T-wave is able to compensate for the morphological differences due to RR dynamics. Moreover, the metrics dw and dNLw are correlated with ΔRR, but da and dNLa are not. The proposed dw and dNLw quantify variations in the temporal domain of the T-wave that are correlated with the RR range and, thus, could possibly reflect the variations of dispersion of repolarization due to changes in heart rate

Comparison of ECG T-wave Duration and morphology restitution markers for sudden cardiac death prediction in chronic heart Failure

An index ofT-wave morphology restitution, TMR, has previously shown to be a sudden cardiac death (SCD) predictor in a population of chronic heart failure (CHF) patients. The aim of this study is to compare the predictive value of TMR, T-wave width restitution (TWR), T-peak-to-end (Tpe) morphology restitution (TpeMR) and Tpe duration restitution (TpeR) indices in the same CHF population. Holter ECG recordings from 651 CHF patients of the MUSIC study, including SCD victims and survivors, were analyzed. TMR was significantly correlated with TWR (ρ=0.66), TpeMR (ρ=0.70) and TpeR (ρ=0.42). SCD victims showed significantly higher values of TMR, TWR and TpeMR than the rest of patients, with TMR being the index most strongly associated with SCD (p=0.002, p=0.006 and p=0.011, respectively). TpeR values were only borderline significantly higher in SCD victims (p=0.061). Univariate Cox analysis showed that TMR was the restitution index with the strongest predictive value (hazard ratio (HR) of 1.466, p < 0.001), followed by TWR (HR of 1.295, p=0.005), TpeR (HR of 1.297, p=0.004) and TpeMR (HR of 1.164, p=0.020). In conclusion, considering the predictive value of the four T-wave restitution indices, TMR is the preferred index for SCD risk stratification, followed by TpeMR. However, the marker TWR could also be used for SCD prediction when computational efficiency is an issue

Interactive effect of beta-adrenergic stimulation and mechanical stretch on low-frequency oscillations of ventricular action potential duration in humans

Ventricular repolarization dynamics are crucial to arrhythmogenesis. Low-frequency oscillations of repolarization have recently been reported in humans and the magnitude of these oscillations proposed to be a strong predictor of sudden cardiac death. Available evidence suggests a role of the sympathetic nervous system. We have used biophysically detailed models integrating ventricular electrophysiology, calcium dynamics, mechanics and β-adrenergic signaling to investigate the underlying mechanisms. The main results were: (1) Phasic beta-adrenergic stimulation (β-AS) at a Mayer wave frequency between 0.03 and 0.15Hz resulted in a gradual decrease of action potential (AP) duration (APD) with concomitant small APD oscillations. (2) After 3-4minutes of phasic β-AS, the mean APD adapted and oscillations of APD became apparent. (3) Phasic changes in haemodynamic loading at the same Mayer wave frequency (a known accompaniment of enhanced sympathetic nerve activity), simulated as variations in the sarcomere length, also induced APD oscillations. (4) The effect of phasic β-AS and haemodynamic loading on the magnitude of APD oscillations was synergistic. (5) The presence of calcium overload and reduced repolarization reserve further enhanced the magnitude of APD oscillations and was accompanied by afterdepolarizations and/or spontaneous APs. In conclusion, low-frequency oscillations of repolarization recently reported in humans were induced by phasic β-AS and phasic mechanical loading, which acted synergistically, and were greatly enhanced by disease-associated conditions, leading to arrhythmogenic events

Influence of heart rate in non-linear HRV indices as a sampling rate effect evaluated on supine and standing

The purpose of this study is to characterize and attenuate the influence of mean heart rate (HR) on nonlinear heart rate variability (HRV) indices (correlation dimension, sample, and approximate entropy) as a consequence of being the HR the intrinsic sampling rate of HRV signal. This influence can notably alter nonlinear HRV indices and lead to biased information regarding autonomic nervous system (ANS) modulation. First, a simulation study was carried out to characterize the dependence of nonlinear HRV indices on HR assuming similar ANS modulation. Second, two HR-correction approaches were proposed: one based on regression formulas and another one based on interpolating RR time series. Finally, standard and HR-corrected HRV indices were studied in a body position change database. The simulation study showed the HR-dependence of non-linear indices as a sampling rate effect, as well as the ability of the proposed HR-corrections to attenuate mean HR influence. Analysis in a body position changes database shows that correlation dimension was reduced around 21% in median values in standing with respect to supine position (p < 0.05), concomitant with a 28% increase in mean HR (p < 0.05). After HR-correction, correlation dimension decreased around 18% in standing with respect to supine position, being the decrease still significant. Sample and approximate entropy showed similar trends. HR-corrected nonlinear HRV indices could represent an improvement in their applicability as markers of ANS modulation when mean HR changes

Interactive effect of beta-adrenergic stimulation and mechanical stretch on low-frequency oscillations of ventricular action potential duration in humans

Ventricular repolarization dynamics are crucial to arrhythmogenesis. Low-frequency oscillations of repolarization have recently been reported in humans and the magnitude of these oscillations proposed to be a strong predictor of sudden cardiac death. Available evidence suggests a role of the sympathetic nervous system. We have used biophysically detailed models integrating ventricular electrophysiology, calcium dynamics, mechanics and ß-adrenergic signaling to investigate the underlying mechanisms. The main results were: (1) Phasic beta-adrenergic stimulation (ß-AS) at a Mayer wave frequency between 0.03 and 0.15 Hz resulted in a gradual decrease of action potential (AP) duration (APD) with concomitant small APD oscillations. (2) After 3-4 minutes of phasic ß-AS, the mean APD adapted and oscillations of APD became apparent. (3) Phasic changes in haemodynamic loading at the same Mayer wave frequency (a known accompaniment of enhanced sympathetic nerve activity), simulated as variations in the sarcomere length, also induced APD oscillations. (4) The effect of phasic ß-AS and haemodynamic loading on the magnitude of APD oscillations was synergistic. (5) The presence of calcium overload and reduced repolarization reserve further enhanced the magnitude of APD oscillations and was accompanied by afterdepolarizations and/or spontaneous APs. In conclusion, low-frequency oscillations of repolarization recently reported in humans were induced by phasic ß-AS and phasic mechanical loading, which acted synergistically, and were greatly enhanced by disease-associated conditions, leading to arrhythmogenic events

Dynamical mechanism for generation of arrhythmogenic early afterdepolarizations in cardiac myocytes: insights from in silico electrophysiological models

We analyze the dynamical mechanisms underlying the formation of arrhythmogenic early afterdepolarizations (EADs) in two mathematical models of cardiac cellular electrophysiology: the Sato et al. biophysically detailed model of a rabbit ventricular myocyte of dimension 27 and a reduced version of the Luo-Rudy mammalian myocyte model of dimension 3. Based on a comparison of the two models, with detailed bifurcation analysis using spike-counting techniques and continuation methods in the simple model and numerical explorations in the complex model, we locate the point where the first EAD originates in an unstable branch of periodic orbits. These results serve as a basis to propose a conjectured scheme involving a hysteresis mechanism with the creation of alternans and EADs in the unstable branch. This theoretical scheme fits well with electrophysiological experimental data on EAD generation and hysteresis phenomena. Our findings open the door to the development of novel methods for pro-arrhythmia risk prediction related to EAD generation without actual induction of EADs