Fractal rigidity by enhanced sympatho-vagal antagonism in heartbeat interval dynamics elicited by central application of corticotropin-releasing factor in mice

The dynamics of heartbeat interval fluctuations were studied in awake unrestrained mice following intracerebroventricular application of the neuropeptide corticotropin-releasing factor (CRF). The cardiac time series derived from telemetric ECG monitoring were analyzed by non-parametric techniques of nonlinear signal processing: delay-vector variance (DVV) analysis, higher-order variability (HOV) analysis, empirical mode decomposition (EMD), multiscale embedding-space decomposition (MESD), multiexponent multifractal (MEMF) analysis. The analyses support the conjecture that cardiac dynamics of normal control mice has both deterministic and stochastic elements, is nonstationary, nonlinear, and exerts multifractal properties. Central application of CRF results in bradycardia and increased variability of the beat-to-beat fluctuations. The altered dynamical properties elicited by CRF reflect a significant loss of intrinsic structural complexity of cardiac control which is due to central neuroautonomic hyperexcitation, i.e., enhanced sympatho-vagal antagonism. The change in dynamical complexity is characterized by an effect referred to as fractal rigidity, leading to a significant impairment of adaptability to extrinsic challenges in a fluctuating environment. The impact of dynamical neurocardiopathy as a major precipiting factor for the propensity of cardiac arrhythmias or sudden cardiac death by unchecked central CRF release in significant acute life events in man is critically discussed.     

Noninvasive technique for measurement of heartbeat regularity in zebrafish (Danio rerio) embryos

Background  

Zebrafish (Danio rerio), due to its optical accessibility and similarity to human, has emerged as model organism for cardiac research. Although various methods have been developed to assess cardiac functions in zebrafish embryos, there lacks a method to assess heartbeat regularity in blood vessels. Heartbeat regularity is an important parameter for cardiac function and is associated with cardiotoxicity in human being. Using stereomicroscope and digital video camera, we have developed a simple, noninvasive method to measure the heart rate and heartbeat regularity in peripheral blood vessels. Anesthetized embryos were mounted laterally in agarose on a slide and the caudal blood circulation of zebrafish embryo was video-recorded under stereomicroscope and the data was analyzed by custom-made software. The heart rate was determined by digital motion analysis and power spectral analysis through extraction of frequency characteristics of the cardiac rhythm. The heartbeat regularity, defined as the rhythmicity index, was determined by short-time Fourier Transform analysis.     

Non-linear dynamic analysis of the cardiac rhythm during transient myocardial ischemia.

Coronary artery occlusions related to myocardial ischemia drive cardiac control system reactions that may lead to heart failure. The purpose of this study was to assess the autonomic nervous system (ANS) response during prolonged percutaneous transluminal coronary angioplasty (PTCA). Continuous ECG data were acquired from 50 patients before and during PTCA, with occlusions in the left anterior descending, left circumflex or right coronary artery. Heart rate variability (HRV) was analyzed for 3-min segments of the R-R interval signal obtained from ECG data. The ANS behavior was evaluated by HRV analysis using fractal-like indices. The fractal scalar exponent alpha(1) and power-law slope beta decreased considerably during PTCA. This indicates that significant reactions of autonomic control of the heart rate occurred during coronary artery occlusions, with a reduction in complexity of the ANS.     

A Cycling Movement Based System for Real-Time Muscle Fatigue and Cardiac Stress Monitoring and Analysis

In this study, we defined a new parameter, referred to as the cardiac stress index (CSI), using a nonlinear detrended fluctuation analysis (DFA) of heart rate (HR). Our study aimed to incorporate the CSI into a cycling based fatigue monitoring system developed in our previous work so the muscle fatigue and cardiac stress can be both continuously and quantitatively assessed for subjects undergoing the cycling exercise. By collecting electrocardiogram (ECG) signals, the DFA scaling exponent α was evaluated on the RR time series extracted from a windowed ECG segment. We then obtained the running estimate of α by shifting a one-minute window by a step of 20 seconds so the CSI, defined as the percentage of all the less-than-one α values, can be synchronously updated every 20 seconds. Since the rating of perceived exertion (RPE) scale is considered as a convenient index which is commonly used to monitor subjective perceived exercise intensity, we then related the Borg RPE scale value to the CSI in order to investigate and quantitatively characterize the relationship between exercise-induced fatigue and cardiac stress. Twenty-two young healthy participants were recruited in our study. Each participant was asked to maintain a fixed pedaling speed at a constant load during the cycling exercise. Experimental results showed that a decrease in DFA scaling exponent α or an increase in CSI was observed during the exercise. In addition, the Borg RPE scale and CSI were positively correlated, suggesting that the factors due to cardiac stress might also contribute to fatigue state during physical exercise. Since the CSI can effectively quantify the cardiac stress status during physical exercise, our system may be used in sports medicine, or used by cardiologists who carried out stress tests for monitoring heart condition in patients with heart diseases.     

Leucomyosuppressin modulates cardiac rhythm in the cockroach Blattella germanica

Several lines of evidence point to leucomyosuppressin (LMS) and myosuppressin-related peptides as inhibitory modulators of heartbeat frequency in arthropods. Previous studies in Blattella germanica demonstrated that heartbeat frequency decreases after ootheca formation, and remains low during the period of ootheca transport. Subsequent work in this cockroach resulted in the characterization of LMS and the cloning and sequencing of its precursor. The present paper describes the activity of LMS on modulation of heartbeat in B. germanica. Assays using semi-isolated heart preparations revealed that LMS reduces heartbeat frequency in a dose dependent manner, at physiological concentrations. Additional experiments showed that LMS inhibits heartbeat rates in vivo. Finally, injection of dsRNA for LMS elicited a decrease in LMS mRNA to virtually undetectable levels and heartbeat frequency increased significantly in females carrying oothecae. These data suggest that LMS contributes to the modulation of cardiac rhythm in B. germanica during the reproductive cycle.     

Non-Invasive Drosophila ECG Recording by Using Eutectic Gallium-Indium Alloy Electrode: A Feasible Tool for Future Research on the Molecular Mechanisms Involved in Cardiac Arrhythmia

Background

Drosophila heart tube is a feasible model for cardiac physiological research. However, obtaining Drosophila electrocardiograms (ECGs) is difficult, due to the weak signals and limited contact area to apply electrodes. This paper presents a non-invasive Gallium-Indium (GaIn) based recording system for Drosophila ECG measurement, providing the heart rate and heartbeat features to be observed. This novel, high-signal-quality system prolongs the recording time of insect ECGs, and provides a feasible platform for research on the molecular mechanisms involved in cardiovascular diseases.

Methods

In this study, two types of electrode, tungsten needle probes and GaIn electrodes, were used respectively to noiselessly conduct invasive and noninvasive ECG recordings of Drosophila. To further analyze electrode properties, circuit models were established and simulated. By using electromagnetic shielded heart signal acquiring system, consisted of analog amplification and digital filtering, the ECG signals of three phenotypes that have different heart functions were recorded without dissection.

Results and Discussion

The ECG waveforms of different phenotypes of Drosophila recorded invasively and repeatedly with n value (n>5) performed obvious difference in heart rate. In long period ECG recordings, non-invasive method implemented by GaIn electrodes acts relatively stable in both amplitude and period. To analyze GaIn electrode, the correctness of GaIn electrode model established by this paper was validated, presenting accuracy, stability, and reliability.

Conclusions

Noninvasive ECG recording by GaIn electrodes was presented for recording Drosophila pupae ECG signals within a limited contact area and signal strength. Thus, the observation of ECG changes in normal and SERCA-depleted Drosophila over an extended period is feasible. This method prolongs insect survival time while conserving major ECG features, and provides a platform for electrophysiological signal research on the molecular mechanism involved in cardiac arrhythmia, as well as research related to drug screening and development.     

Fractal dimension and vessel complexity in patients with cerebral arteriovenous malformations

The fractal dimension (FD) can be used as a measure for morphological complexity in biological systems. The aim of this study was to test the usefulness of this quantitative parameter in the context of cerebral vascular complexity. Fractal analysis was applied on ten patients with cerebral arteriovenous malformations (AVM) and ten healthy controls. Maximum intensity projections from Time-of-Flight MRI scans were analyzed using different measurements of FD, the Box-counting dimension, the Minkowski dimension and generalized dimensions evaluated by means of multifractal analysis. The physiological significance of this parameter was investigated by comparing values of FD first, with the maximum slope of contrast media transit obtained from dynamic contrast-enhanced MRI data and second, with the nidus size obtained from X-ray angiography data. We found that for all methods, the Box-counting dimension, the Minkowski dimension and the generalized dimensions FD was significantly higher in the hemisphere with AVM compared to the hemisphere without AVM indicating that FD is a sensitive parameter to capture vascular complexity. Furthermore we found a high correlation between FD and the maximum slope of contrast media transit and between FD and the size of the central nidus pointing out the physiological relevance of FD. The proposed method may therefore serve as an additional objective parameter, which can be assessed automatically and might assist in the complex workup of AVMs.     

Assessment of Interaction Between Cardio-Respiratory Signals Using Directed Coherence on Healthy Subjects During Postural Change

PurposeTo detect and quantify the directional interaction changes between cardio-respiratory system during postural change.MethodTraditional frequency domain analysis based on power spectrum and coherence are insufficient to quantify nonlinear structures and complexity of physiological subsystems. Recently, Granger causality is found as preferable method for evaluation of causality i.e., directional interaction. Frequency domain Granger causality based on directed coherence has been used in this study to identify directional interaction between cardiac and respiratory signal during postural change from supine to standing for healthy subjects.ResultECG and respiration signal are recorded for this study. The beat-to-beat variability series from ECG provides heart rate (RR) and the respiration amplitude corresponds to RESP time series. It was observed that respiration is responsible for the changes in ECG signal during supine position as compared to standing. The outflow of information from RESP to RR increases during supine results in stronger interaction but reduces during standing result in reduction of interaction. Similarly, the effect of RR on RESP is found significant only during standing.ConclusionThe proposed directed coherence approach detects the cardio-respiratory regulation during postural change and provide information about coupling changes during this transition.     

基于复杂度的心率变异性分析研究进展

心率变异性（HRV）是当前心电图分析的一个前沿热点,它反映了交感神经和副交感神经对心血管系统的综合调节作用,是评价心血管系统功能的重要指标。随着非线性动力学和复杂性科学的发展,HRV信号被普遍认为是混沌或含有混沌成分的信号。复杂度是用来表征一个心率非线性动力学系统复杂程度的量度,以其简单快速的优点引起了众多研究者的兴趣,并广泛应用于心率变异性分析。本文综述了国内外复杂度算法的研究进展及基于复杂度的心率变异性分析的临床应用及前景。     

Dual effects of dopamine on the adult heart of the isopod crustacean Ligia exotica

In the adult heart of the isopod crustacean Ligia exotica, the cardiac ganglion acts as the primary pacemaker with the myocardium having a latent pacemaker property. We show several lines of evidence that dopamine modulates the heartbeat of adult L. exotica affecting both pacemaker sites in the heart. Dopamine caused positive chronotropic (frequency increase) and inotropic (amplitude increase) effects on the heartbeat in a concentration dependent manner. The time courses of these effects were considerably different and the inotropic effect appeared later and lasted longer than the chronotropic effect. Dopamine rapidly increased the frequency of the bursting activity in the cardiac ganglion neurons and each impulse burst of the cardiac ganglion was always followed by a heartbeat. Moreover, dopamine slowly increased the amplitude and duration of the action potential plateau (plateau potential) of the myocardium. When the myocardial pacemaker activity was induced by application of tetrodotoxin, which suppresses cardiac ganglion activity, dopamine slowly increased the amplitude and duration of the myocardial plateau potential while decreasing its frequency. These results suggest that dopamine modulates the heartbeat in adult L. exotica producing a dual effect on the two pacemaker sites in the heart, the cardiac ganglion and myocardium.     

Microwave effects on isolated chick embryo hearts

This study was designed to examine the effects of microwaves on the electric activity of hearts as a means of elucidating interactive mechanisms of nonionizing radiation with cardiac tissue. Experiments were performed on isolated hearts of 9-12-day-old chick embryos placed in small petri dishes. Oxygenated isotonic Ringer's solution at 37 degrees C permitted heart survival. Samples were irradiated at 2.45 GHz with a power density of 3 mW/cm2. The heart signal was detected with a glass micropipet inserted into the sinoatrial node and examined by means of a Berg-Fourier analyzer. Pulsed microwaves caused the locking of the heartbeat to the modulation frequency, whereas continuous wave irradiation might have induced slight bradycardia. Pulsed fields induced stimulation or regularization of the heartbeat in arrhythmia, fibrillation, or arrest of the heart.     

跳动心脏的心电仿真模型建构

以往的心电仿真研究都没有考虑在一个心动周期内,因为心脏跳动而引起的偶极子位置变化的实际情况,从而造成其结果输出的不可避免的误差,在心脏电生理和心脏动力学分析的基础上,对原有的心脏电仿真模型施加动力学影响,从而构建了新的跳动心脏模型。在这两个模型上进行了正常心脏和心肌缺血心脏的仿真试验后,对比两个心电模型的仿真输出,发现新的心脏模型有效提高了仿真精度,对于严重心肌缺血和轻微心肌缺血的识别分别有不同程度的改善。这项研究证实了动力学因素 在心电模型建构中的重要性,为心电正问题和逆问题研究的进一步开展 提供了新的思路和方向。     

A Comparison of ECG Signal Pre-processing Using FrFT,FrWT and IPCA for Improved Analysis

ObjectiveElectrocardiogram (ECG) is a diagnostic tool for recording electrical activities of the human heart non-invasively. It is detected by electrodes placed on the surface of the skin in a conductive medium. In medical applications, ECG is used by cardiologists to observe heart anomalies (cardiovascular diseases) such as abnormal heart rhythms, heart attacks, effects of drug dosage on subject's heart and knowledge of previous heart attacks. Recorded ECG signal is generally corrupted by various types of noise/distortion such as cardiac (isoelectric interval, prolonged depolarization and atrial flutter) or extra cardiac (respiration, changes in electrode position, muscle contraction and power line noise). These factors hide the useful information and alter the signal characteristic due to low Signal-to-Noise Ratio (SNR). In such situations, any failure to judge the ECG signal correctly may result in a delay in the treatment and harm a subject (patient) health. Therefore, appropriate pre-processing technique is necessary to improve SNR to facilitate better treatment to the subject. Effects of different pre-processing techniques on ECG signal analysis (based on R-peaks detection) are compared using various Figures of Merit (FoM) such as sensitivity (Se), accuracy (Acc) and detection error rate (DER) along with SNR.MethodsIn this research article, a new fractional wavelet transform (FrWT) has been proposed as a pre-processing technique in order to overcome the disadvantages of other existing commonly used techniques viz. wavelet transform (WT) and the fractional Fourier transform (FrFT). The proposed FrWT technique possesses the properties of multiresolution analysis and represents signal in the fractional domain which consists of representation in terms of rotation of signals in the time–frequency plane. In the literature, ECG signal analysis has been improvised using statistical pre-processing techniques such as principal component analysis (PCA), and independent component analysis (ICA). However, both PCA and ICA are prone to suffer from slight alterations in either signal or noise, unless the basis functions are prepared with a worldwide set of ECG. Independent Principal Component Analysis (IPCA) has been used to overcome this shortcoming of PCA and ICA. Therefore, in this paper three techniques viz. FrFT, FrWT and IPCA are selected for comparison in pre-processing of ECG signals.ResultsThe selected methods have been evaluated on the basis of SNR, Se, Acc and DER of the detected ECG beats. FrWT yields the best results among all the methods considered in this paper; 34.37dB output SNR, 99.98% Se, 99.96% Acc, and 0.036% DER. These results indicate the quality of biology-related information retained from the pre-processed ECG signals for identifying different heart abnormalities.ConclusionCorrect analysis of the acquired ECG signal is the main challenge for cardiologist due to involvement of various types of noises (high and low frequency). Twenty two real time ECG records have been evaluated based on various FoM such as SNR, Se, Acc and DER for the proposed FrWT and existing FrFT and IPCA preprocessing techniques. Acquired real-time ECG database in normal and disease situations is used for the purpose. The values of FoMs indicate high SNR and better detection of R-peaks in a ECG signal which is important for the diagnosis of cardiovascular disease. The proposed FrWT outperforms all other techniques and holds both analytical attributes of the actual ECG signal and alterations in the amplitudes of various ECG waveforms adequately. It also provides signal portrayals in the time-fractional-frequency plane with low computational complexity enabling their use practically for versatile applications.     

Bench and mathematical modeling of the effects of breathing a helium/oxygen mixture on expiratory time constants in the presence of heterogeneous airway obstructions

Background

Vectorcardiogram (VCG) signals monitor both spatial and temporal cardiac electrical activities along three orthogonal planes of the body. However, the absence of spatiotemporal resolution in conventional VCG representations is a major impediment for medical interpretation and clinical usage of VCG. This is especially so because time-domain features of 12-lead ECG, instead of both spatial and temporal characteristics of VCG, are widely used for the automatic assessment of cardiac pathological patterns.

Materials and methods

We present a novel representation approach that captures critical spatiotemporal heart dynamics by displaying the real time motion of VCG cardiac vectors in a 3D space. Such a dynamic display can also be realized with only one lead ECG signal (e.g., ambulatory ECG) through an alternative lag-reconstructed ECG representation from nonlinear dynamics principles. Furthermore, the trajectories are color coded with additional dynamical properties of space-time VCG signals, e.g., the curvature, speed, octant and phase angles to enhance the information visibility.

Results

In this investigation, spatiotemporal VCG signal representation is used to characterize various spatiotemporal pathological patterns for healthy control (HC), myocardial infarction (MI), atrial fibrillation (AF) and bundle branch block (BBB). The proposed color coding scheme revealed that the spatial locations of the peak of T waves are in the Octant 6 for the majority (i.e., 74 out of 80) of healthy recordings in the PhysioNet PTB database. In contrast, the peak of T waves from 31.79% (117/368) of MI subjects are found to remain in Octant 6 and the rest (68.21%) spread over all other octants. The spatiotemporal VCG signal representation is shown to capture the same important heart characteristics as the 12-lead ECG plots and more.

Conclusions

Spatiotemporal VCG signal representation is shown to facilitate the characterization of space-time cardiac pathological patterns and enhance the automatic assessment of cardiovascular diseases.     

Heartbeat patterns during the postembryonic development of Drosophila melanogaster

Pulsations of the dorsal vessel were recorded in vivo during the whole postembryonic development of D. melanogaster, by means of a newly invented, pulse-light opto-cardiographic method. The young larvae of the 1st and 2nd instars submerged in the feeding medium exhibited extremely high rates of heartbeat, 7Hz at room temperature. These values are among the highest rates of heartbeat ever recorded in the animal kingdom. The fully grown larvae of the 3rd instar showed approximately half of the maximum heartbeat rate (3.5-4Hz), which became stabilized after pupariation to 2.5-2.7Hz.The larval heartbeat was always uni-directional, in the forward-oriented or anterograde direction and it was almost continuous. The slowly disintegrating, old larval heart used to beat at the constant frequency of 2.5-2.7Hz until complete cessation of all cardiac functions in 1-day-old puparium. In spite of the persisting constant heartbeat frequency, the transformation process of the larval heart was associated with successively decreasing amplitude of the systolic contractions and with the prolongation of the resting periods. The newly formed heart of the pupal-adult structure exhibited a qualitatively new pattern of heartbeat activity, which was manifested by periodic reversal of the heartbeat with the faster anterograde and slower retrograde phases. The frequencies of both of these reciprocal cardiac pulsations gradually increased during the advanced pharate adult period, reaching the values of 4-5Hz at the time of adult eclosion. Adult males and females also exhibited a perfect pattern of heartbeat reversal, with still very high rates of the anterograde heartbeat, in the range of 5-6Hz. In addition to the cardiac functions, we have recorded several kinds of extracardiac pulsations, which often interfered severely with the recordings of the heartbeat. There were strong, irregular extracardiac pulsations of a neurogenic nature (somatic muscles, oral armature) and relatively slow extracardiac pulsations of a myogenic nature (intestinal peristaltics, 0.2-0.3Hz). The extracardiac and cardiac pulsations were independent, their functions were not correlated. A possibility of creating new challenges in combination of molecular biology with the functional physiology of the heart have been discussed.     

Cardioacceleratory Neurons of the Isopod Crustacean, Ligia exotica: Visualization of Peripheral Projection onto the Heart Muscle

Innervation of the heart muscle by the cardioacceleratory neurons was morphologically and electrophysiologically examined in the isopod crustacean, Ligia exotica. Intracellular injection of neurobiotin into the first and second cardioacceleratory neurons (CA1 and CA2) revealed their peripheral axonal projections. Inside the heart, the CA1 and CA2 axons ran along the trunk of the cardiac ganglion. Finely arborized branches with many varicosities arose from the axon and projected over the heart muscle. Stimulation of either the CA1 or CA2 axon caused an overall depolarization in the muscle of a quiescent heart. The amplitude of the depolarization increased with increasing stimulus frequency. During stimulation, the membrane resistance of the heart muscle decreased. In a beating heart, the cardioacceleratory nerve stimulation caused multiple effects on the heart muscle activity and the heartbeat. The results suggest that the cardioacceleratory neurons of Ligia exotica regulate the amplitude of the heartbeat (inotropic effect) and the heart tonus (tonotropic effect) via the synaptic contacts on the heart muscle, while the heartbeat frequency (chronotropic effect) is regulated via the synapses on the cardiac ganglion neurons.     

Mitochondrial ca(2+) signaling and cardiac apoptosis

The broad significance of apoptosis in the cardiovascular system only began to be recognized more widely recently. Apoptotic cell death is a normal component of postnatal morphogenesis of the human cardiac conduction system and may also be involved in the pathogenesis of a variety of cardiovascular diseases, including heart failure, myocardial infarction and atherosclerosis. Recently, it has become evident that mitochondria play important role in the signaling machinery of apoptotic cell death by releasing several apoptotic factors such as cytochrome c, apoptosis-inducing factor and procaspases. Furthermore, calcium signals have been identified as one of the major signals that converge on mitochondria to trigger the mitochondrion-dependent pathway of the apoptotic cell death. Calcium signals are also important in the physiological control of mitochondrial energy metabolism and it has not yet been explored how Ca(2+) turns from a signal for life to a signal for death. Since large elevations of cytosolic [Ca(2+)] ([Ca(2+)](c)) occur during each heartbeat in cardiac myocytes and these [Ca(2+)](c) signals may efficiently propagate to the mitochondria, the Ca(2+)-dependent mitochondrial pathways of apoptosis can be particularly important in the heart. This review is concerned with the role of mitochondrial Ca(2+) signaling in the control of cardiac apoptosis.     

Dynamical analysis of the calcium signaling pathway in cardiac myocytes based on logarithmic sensitivity analysis

Many cellular functions are regulated by the Ca(2+) signal which contains specific information in the form of frequency, amplitude, and duration of the oscillatory dynamics. Any alterations or dysfunctions of components in the calcium signaling pathway of cardiac myocytes may lead to a diverse range of cardiac diseases including hypertrophy and heart failure. In this study, we have investigated the hidden dynamics of the intracellular Ca(2+) signaling and the functional roles of its regulatory mechanism through in silico simulations and parameter sensitivity analysis based on an experimentally verified mathematical model. It was revealed that the Ca(2+) dynamics of cardiac myocytes are determined by the balance among various system parameters. Moreover, it was found through the parameter sensitivity analysis that the self-oscillatory Ca(2+) dynamics are most sensitive to the Ca(2+) leakage rate of the sarcolemmal membrane and the maximum rate of NCX, suggesting that these two components have dominant effects on circulating the cytosolic Ca(2+).     

Fractal dynamics in circadian cardiac time series of corticotropin-releasing factor receptor subtype-2 deficient mice

Non-linear fractal analysis of circadian 24 hr heartbeat interval time series was performed in corticotropin releasing factor receptor-subtype 2 (CRFR2) deficient mice. We hypothesized that, as a result of its central as well as its peripheral expression, CRFR2 would mediate or interfere with the circadian rhythmicity. The dynamical properties of cardiac interbeat intervals were expected to be different between CRFR2 (+/+) and CRFR2 (–/–) mice when studied over an extended circadian 24 hr cycle. The dynamics of neurocardiac control were found to remain remarkably stable throughout the circadian cycle. In disagreement with the initial hypothesis, the dynamical properties underlying the cardiac control process were common to both CRFR2 (+/+) and CRFR2 (–/–) mice suggesting that control of heart rate does not rely on the elaborate interaction of the CRFR2-sensor and its intrinsic feedback arrangement. Lack of expression of CRFR2 would not compromise cardiac control and its dynamical output or is subserved by other, unknown mechanisms. Functional integrity of CRFR2 would not constitute an indispensable requirement of physiologic cardiac control. The circadian rhythm of heart rate is generated centrally and is independent of expression of CRFR2. While `normal' strain C57BL/6N mice exhibit a circadian dark/light cycle of heart rate, absence of circadian fluctuations in transgenic CRFR2-mice (both +/+ and –/–) and `normal' strain C57BL/6J mice points at the importance of other deficiencies that may be related to a common genetic background. Mutant mice that share a common 129SvJ- or C57BL/6J-derived genetic background may not present an optimal model for physiological studies of cardiovascular control.     

Complex dynamics underlying the human electrocardiogram

Sequences of different human cardiac rhythms terminating in ventricular fibrillation have been studied, both qualitatively and quantitively, with methods of nonlinear dynamics. The analysis has been applied to ECG epochs belonging to rhythms of increasing electrocardiographic irregularity: from sinus rhythm to prefibrillatory rhythms and then to ventricular fibrillation. The phase portraits of these rhythms have been reconstructed from the ECG recording with the time-delay technique, and their correlation dimensions have been estimated with the algorithm of Grassberger and Procaccia (1983a, b). Different cardiac rhythms exhibit different correlation dimensions that describe the corresponding degrees of complexity. The correlation dimension increases as one proceeds from sinus rhythm to fully developed ventricular fibrillation via intermediate rhythms. The fully developed ventricular fibrillation shows the highest degree of complexity. The dimensional analysis supports the existence of complex dynamics underlying different cardiac rhythms and reveals an increase in dimensional complexity corresponding to an increase in electrocardiographic irregularity. Our results indicate that nonlinear dynamics may be used to assess various dynamic states of the heart and may offer a non-invasive tool to investigate the complex dynamic phenomena occuring during arrhythmia.