Biomedical subjects

Ary L Goldberger

Publications and source records attributed to Ary L Goldberger.

At least 19 recordsLinked to original sources

PubMed2007

Short-term fasting-induced autonomic activation and changes in catecholamine levels are not mediated by changes in leptin levels in healthy humans.

OBJECTIVE: In animal models, the adipocyte-secreted hormone leptin increases energy expenditure by increasing sympathetic outflow but its role in humans remains to be elucidated. We evaluated whether inducing hypoleptinaemia (with and without administration of leptin at replacement doses) for 3 days would influence catecholamine levels and sympathetic and parasympathetic activity in healthy humans. METHODS: We studied six normal-weight subjects in the General Clinical Research Center (GCRC) under three conditions: baseline fed state (control study) and two 72-h fasting studies (to decrease leptin levels), with administration of either placebo or replacement-dose recombinant methionyl human leptin (r-metHuLeptin) in a randomized, double-blind fashion. In each condition, 24-h urinary catecholamine levels, heart rate and heart rate variability (HRV), a standard tool for assessing cardiac autonomic modulation, were measured. RESULTS: Study parameters remained stable during the control condition and the baseline assessment of all three studies. In response to 72-h fasting, which decreased serum leptin levels by 80%, 24-h urinary norepinephrine and dopamine levels and heart rate increased while cardiac vagal modulation decreased (all P < 0.05). Replacement-dose r-metHuLeptin to keep leptin levels within the physiological range during fasting did not alter fasting-associated changes in heart rate, catecholamine levels or cardiac vagal tone. CONCLUSIONS: The findings of this controlled, interventional study indicate that changes in heart rate, catecholamine levels and cardiac vagal modulation associated with 72-h fasting are independent of regulation by leptin. Thus, changes in leptin levels within the physiological range do not seem to play a role in regulating autonomic function during short-term starvation in healthy humans.

Adult↗

PubMed2006

The rule of bigeminy revisited: analysis in sudden cardiac death syndrome.

BACKGROUND: The rule of bigeminy is commonly explained by a reentrant mechanism. We hypothesize that in patients with prolonged ventricular repolarization, the rule of bigeminy may be caused by premature ventricular complexes (PVCs) due to early afterdepolarizations. We evaluated these ventricular arrhythmias over extended periods in patients with sudden cardiac death syndrome. METHODS: The electrocardiographic (ECG) characteristics of 15 recordings from the PhysioNet Sudden Cardiac Death Holter Database were analyzed for the persistence of bigeminy, interaction between the underlying cardiac rhythm and the coupling interval, and influence of a prolonged initiating RR cycle on the self-perpetuation of the arrhythmias. RESULTS: Eight (53%) patients had classic torsade de pointes (TdP), 5 (33%) had other polymorphic ventricular tachycardia (VT), and 2 (13%) had monomorphic VT. Group A, which comprised 6 of the patients with TdP, had the following ECG tetrad: (1) frequent ventricular bigeminy (>5% of total ventricular arrhythmias), (2) long corrected QT interval (>0.5 second), (3) relatively fixed coupling interval, and (4) onset of bigeminy (n = 4) and TdP (n = 6) after a short-long RR sequence. Patients in group A had slower heart rates (mean RR = 1.12 +/- 0.26 vs 0.77 +/- 0.13 seconds, P < .01), longer QT intervals (corrected QT = 0.57 +/- 0.06 vs 0.45 +/- 0.06 second; P < .01) and more cases with prominent U waves (83% vs 33%, P < .05) than patients in group B (n = 9), composed of patients who had other types of VT, or TdP without frequent bigeminy. CONCLUSIONS: We identified a set of ECG characteristics that supports the notion that premature ventricular complexes during self-perpetuating ventricular bigeminy ("rule of bigeminy") in long QT syndromes may be due to early afterdepolarizations.

Adult↗

PubMed2006

Giles f. Filley lecture. Complex systems.

Physiologic systems in health and disease display an extraordinary range of temporal behaviors and structural patterns that defy understanding based on linear constructs, reductionist strategies, and classical homeostasis. Application of concepts and computational tools derived from the contemporary study of complex systems, including nonlinear dynamics, fractals and "chaos theory," is having an increasing impact on biology and medicine. This presentation provides a brief overview of an emerging area of biomedical research, including recent applications to cardiopulmonary medicine and chronic obstructive lung disease.

Biology↗

PubMed2005

Broken asymmetry of the human heartbeat: loss of time irreversibility in aging and disease.

Time irreversibility, a fundamental property of nonequilibrium systems, should be of importance in assessing the status of physiological processes that operate over a wide range of scales. However, measurement of this property in living systems has been limited. We provide a computational method derived from basic physics assumptions to quantify time asymmetry over multiple scales and apply it to the human heartbeat time series in health and disease. We find that the multiscale time asymmetry index is highest for a time series from young subjects and decreases with aging or heart disease. Loss of time irreversibility may provide a new way of assessing the functionality of living systems that operate far from equilibrium.

Aging↗

PubMed2005

Multiscale entropy analysis of biological signals.

Traditional approaches to measuring the complexity of biological signals fail to account for the multiple time scales inherent in such time series. These algorithms have yielded contradictory findings when applied to real-world datasets obtained in health and disease states. We describe in detail the basis and implementation of the multiscale entropy (MSE) method. We extend and elaborate previous findings showing its applicability to the fluctuations of the human heartbeat under physiologic and pathologic conditions. The method consistently indicates a loss of complexity with aging, with an erratic cardiac arrhythmia (atrial fibrillation), and with a life-threatening syndrome (congestive heart failure). Further, these different conditions have distinct MSE curve profiles, suggesting diagnostic uses. The results support a general "complexity-loss" theory of aging and disease. We also apply the method to the analysis of coding and noncoding DNA sequences and find that the latter have higher multiscale entropy, consistent with the emerging view that so-called "junk DNA" sequences contain important biological information.

Adult↗

PubMed2005

Genomic classification using an information-based similarity index: application to the SARS coronavirus.

Measures of genetic distance based on alignment methods are confined to studying sequences that are conserved and identifiable in all organisms under study. A number of alignment-free techniques based on either statistical linguistics or information theory have been developed to overcome the limitations of alignment methods. We present a novel alignment-free approach to measuring the similarity among genetic sequences that incorporates elements from both word rank order-frequency statistics and information theory. We first validate this method on the human influenza A viral genomes as well as on the human mitochondrial DNA database. We then apply the method to study the origin of the SARS coronavirus. We find that the majority of the SARS genome is most closely related to group 1 coronaviruses, with smaller regions of matches to sequences from groups 2 and 3. The information based similarity index provides a new tool to measure the similarity between datasets based on their information content and may have a wide range of applications in the large-scale analysis of genomic databases.

Base Sequence↗

PubMed2005

An electrocardiogram-based technique to assess cardiopulmonary coupling during sleep.

STUDY OBJECTIVES: To evaluate a new automated measure of cardiopulmonary coupling during sleep using a single-lead electrocardiographic signal. DESIGN: Using training and test datasets of 35 polysomnograms each, we assessed the correlations of an electrocardiogram-based measure of cardiopulmonary interactions with respect to standard sleep staging, as well as to the cyclic alternating pattern classification. The pattern of coupling in 15 healthy individuals was also assessed. SETTING: American Academy of Sleep Medicine Accredited Sleep Disorders Center. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: From a continuous, single-lead electrocardiogram, we extracted both the normal-to-normal sinus interbeat interval series and a corresponding electrocardiogram-derived respiration signal. Employing Fourier-based techniques, the product of the coherence and cross-power of these 2 simultaneous signals was used to generate a spectrographic representation of cardiopulmonary coupling dynamics during sleep. This technique shows that non-rapid eye movement sleep in adults demonstrates spontaneous abrupt transitions between high- and low-frequency cardiopulmonary coupling regimes, which have characteristic electroencephalogram, respiratory, and heart-rate variability signatures in both health and disease. Using the kappa statistic, agreement with standard sleep staging was poor (training set 62.7%, test set 43.9%) but higher with cyclic alternating pattern scoring (training set 74%, test set 77.3%). CONCLUSIONS: A sleep spectrogram derived from information in a single-lead electrocardiogram can be used to dynamically track cardiopulmonary interactions. The 2 distinct (bimodal) regimes demonstrate a closer relationship with visual cyclic alternating pattern and non-cyclic alternating pattern states than with standard sleep stages. This technique may provide a complementary approach to the conventional characterization of graded non-rapid eye movement sleep stages.

Electroencephalography↗

PubMed2004

Gait unsteadiness and fall risk in two affective disorders: a preliminary study.

BACKGROUND: In older adults, depression has been associated with increased fall risk, but the reasons for this link are not fully clear. Given parallels between major depression and Parkinson's disease, we hypothesized that major depression and related affective disorders would be associated with impairment in the ability to regulate the stride-to-stride fluctuations in gait cycle timing. METHODS: We measured stride-to-stride fluctuations of patients with two forms of mood disorders, unipolar major depressive disorder (MDD) and bipolar disorder, and compared their gait to that of a healthy control group. The primary outcomes were two measures of gait unsteadiness that have been associated with fall risk: stride time variability and swing time variability. RESULTS: Compared to the control group, the two patient groups tended to walk more slowly and with decreased swing time and increased stride time. However, none of these differences was statistically significant. Compared to the control group, swing time variability was significantly larger in the subjects with bipolar disorder (p < 0.0001) and in the subjects with MDD (p < 0.0004). CONCLUSIONS: Patients with MDD and patients with bipolar disorder display gait unsteadiness. This perturbation in gait may provide a mechanistic link connecting depression and falls. The present findings also suggest the possibility that measurement of variability of gait may provide a readily quantifiable objective approach to monitoring depression and related affective disorders.

Accidental Falls↗

PubMed2004

Emergence of complex dynamics in a simple model of signaling networks.

Various physical, social, and biological systems generate complex fluctuations with correlations across multiple time scales. In physiologic systems, these long-range correlations are altered with disease and aging. Such correlated fluctuations in living systems have been attributed to the interaction of multiple control systems; however, the mechanisms underlying this behavior remain unknown. Here, we show that a number of distinct classes of dynamical behaviors, including correlated fluctuations characterized by 1/f scaling of their power spectra, can emerge in networks of simple signaling units. We found that, under general conditions, complex dynamics can be generated by systems fulfilling the following two requirements, (i) a "small-world" topology and (ii) the presence of noise. Our findings support two notable conclusions. First, complex physiologic-like signals can be modeled with a minimal set of components; and second, systems fulfilling conditions i and ii are robust to some degree of degradation (i.e., they will still be able to generate 1/f dynamics).

Mathematics↗

PubMed2004

Multimodal pressure-flow method to assess dynamics of cerebral autoregulation in stroke and hypertension.

BACKGROUND: This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals. METHODS: We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 +/- 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound. RESULTS: A new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts. CONCLUSION: In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure.

Blood Flow Velocity↗

PubMed2004

Effects of tai chi mind-body movement therapy on functional status and exercise capacity in patients with chronic heart failure: a randomized controlled trial.

PURPOSE: To examine the effects of a 12-week tai chi program on quality of life and exercise capacity in patients with heart failure. METHODS: Thirty patients with chronic stable heart failure and left ventricular ejection fraction < or =40% (mean [+/- SD] age, 64 +/- 13 years; mean baseline ejection fraction, 23% +/- 7%; median New York Heart Association class, 2 [range, 1 to 4]) were randomly assigned to receive usual care (n = 15), which included pharmacologic therapy and dietary and exercise counseling, or 12 weeks of tai chi training (n = 15) in addition to usual care. Tai chi training consisted of a 1-hour class held twice weekly. Primary outcomes included quality of life and exercise capacity. Secondary outcomes included serum B-type natriuretic peptide and plasma catecholamine levels. For 3 control patients with missing data items at 12 weeks, previous values were carried forward. RESULTS: At 12 weeks, patients in the tai chi group showed improved quality-of-life scores (mean between-group difference in change, -25 points, P = 0.001), increased distance walked in 6 minutes (135 meters, P = 0.001), and decreased serum B-type natriuretic peptide levels (-138 pg/mL, P = 0.03) compared with patients in the control group. A trend towards improvement was seen in peak oxygen uptake. No differences were detected in catecholamine levels. CONCLUSION: Tai chi may be a beneficial adjunctive treatment that enhances quality of life and functional capacity in patients with chronic heart failure who are already receiving standard medical therapy.

Aged↗

PubMed2004

Heart rate dynamics during three forms of meditation.

OBJECTIVE: This study was designed to quantify and compare the instantaneous heart rate dynamics and cardiopulmonary interactions during sequential performance of three meditation protocols with different breathing patterns. BACKGROUND: We analyzed beat-to-beat heart rate and continuous breathing signals from 10 experienced meditators (4 females; 6 males; mean age 42 years; range 29-55 years) during three traditional interventions: relaxation response, breath of fire, and segmented breathing. RESULTS: Heart rate and respiratory dynamics were generally similar during the relaxation response and segmented breathing. We observed high amplitude, low frequency (approximately 0.05-0.1 Hz) oscillations due to respiratory sinus arrhythmia during both the relaxation response and segmented breathing, along with a significantly (p<0.05) increased coherence between heart rate and breathing during these two maneuvers when compared to baseline. The third technique, breath of fire, was associated with a different pattern of response, marked by a significant increase in mean heart rate with respect to baseline (p<0.01), and a significant decrease in coherence between heart rate and breathing (p<0.05). CONCLUSIONS: These findings suggest that different meditative/breathing protocols may evoke common heart rate effects, as well as specific responses. The results support the concept of a "meditation paradox," since a variety of relaxation and meditative techniques may produce active rather than quiescent cardiac dynamics, associated with prominent low frequency heart rate oscillations or increases in mean resting heart rate. These findings also underscore the need to critically assess traditional frequency domain heart rate variability parameters in making inferences about autonomic alterations during meditation with slow breathing.

Adult↗

PubMed2003

Sinus versus nonsinus tachycardia in the emergency department: importance of age and heart rate.

BACKGROUND: The emergency department diagnosis of sinus versus nonsinus tachycardia is an important clinical challenge. The objective of this study was to identify subjects with a high prevalence of nonsinus tachycardia. METHODS: Heart rate and cardiac rhythm were prospective reviewed in 500 consecutive patients with heart rate > or = 100 beats/min in a busy emergency department. A predictive model based on age and heart rate was then developed to identify the probability of nonsinus tachycardia. RESULTS: As age and heart rate increased, nonsinus tachycardias became more frequent. The probability of nonsinus tachycardia in a subject > or = 71 years with heart rate > or = 141 beats/minute was 93%, compared to only three percent in a subject < or = 50 years with heart rate 100-120 beats/minute. A simple point score system based on age and heart rate helps predict the probability of sinus tachycardia versus nonsinus tachycardia. CONCLUSION: Nonsinus tachycardia is significantly more common than sinus tachycardia in elderly patients in the emergency department. The diagnosis of sinus tachycardia becomes much less likely as age and heart rate increase.

Adolescent↗

PubMed2003

Linguistic analysis of the human heartbeat using frequency and rank order statistics.

Complex physiologic signals may carry unique dynamical signatures that are related to their underlying mechanisms. We present a method based on rank order statistics of symbolic sequences to investigate the profile of different types of physiologic dynamics. We apply this method to heart rate fluctuations, the output of a central physiologic control system. The method robustly discriminates patterns generated from healthy and pathologic states, as well as aging. Furthermore, we observe increased randomness in the heartbeat time series with physiologic aging and pathologic states and also uncover nonrandom patterns in the ventricular response to atrial fibrillation.

Adult↗

PubMed2003

PhysioNet: an NIH research resource for complex signals.

The Research Resource for Complex Physiologic Signals, supported by the National Institutes of Health (NIH), is intended to promote and facilitate investigations in the study of cardiovascular and other complex biomedical signals. The resource website (www.physionet.org) has 3 interdependent components: 1) PhysioBank is an archive of well-characterized digital recordings of physiologic signals and related data, including databases of electrocardiogram and heart rate time series from patients with heart failure, coronary disease, sleep apnea syndromes, and cardiac arrhythmias; 2) PhysioToolkit is a library of open-source software for physiologic signal processing and analysis; and 3) PhysioNet, for which the resource is named, is an on-line forum for dissemination and exchange of recorded biomedical signals and open-source software for analyzing them. PhysioNet, in cooperation with the annual Computers in Cardiology conference, hosts a series of challenges inviting participants to tackle clinically interesting problems that are either unsolved or not well solved. PhysioNet invites contributions of databases and software from the biomedical community.

Atrial Fibrillation↗

PubMed2003

Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison with leptin, circulating soluble leptin receptor, and cortisol patterns.

Adiponectin is an abundant serum adipokine secreted exclusively from differentiated adipocytes, which plays an important role in regulating insulin sensitivity. The dynamics of circulating adiponectin concentrations have yet to be systematically investigated. We sought to determine whether serum adiponectin levels exhibit diurnal or ultradian rhythms in healthy normal-weight men and to compare the 24-h profile of adiponectin fluctuations with those of leptin, leptin-binding protein (sOB-R), and cortisol. We collected blood samples at 15-min intervals over 24 h from six subjects receiving an isocaloric diet, and we measured adiponectin, leptin, sOB-R, and cortisol levels. Fourier and cross-correlation analyses were performed on these time series to study diurnal variations, and the Cluster7 program was used for pulsatility analysis. Circulating adiponectin and sOB-R levels exhibited ultradian pulsatility as well as a diurnal variation with a significant decline at night, reaching a nadir in the early morning. The 24-h variations of serum adiponectin and sOB-R were nearly identical and followed those of cortisol after a few hours, but were out-of-phase with leptin diurnal rhythms. These data suggest that adiponectin and sOB-R levels might be influenced by common regulatory factors and challenge the notion that cortisol may have a direct inhibitory effect on adiponectin in humans.

Activity Cycles↗

PubMed2002

Complex patterns of abnormal heartbeats.

Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

Arrhythmias, Cardiac↗

PubMed2002

Multiscale entropy analysis of complex physiologic time series.

There has been considerable interest in quantifying the complexity of physiologic time series, such as heart rate. However, traditional algorithms indicate higher complexity for certain pathologic processes associated with random outputs than for healthy dynamics exhibiting long-range correlations. This paradox may be due to the fact that conventional algorithms fail to account for the multiple time scales inherent in healthy physiologic dynamics. We introduce a method to calculate multiscale entropy (MSE) for complex time series. We find that MSE robustly separates healthy and pathologic groups and consistently yields higher values for simulated long-range correlated noise compared to uncorrelated noise.

Algorithms↗