David R. Rigney

Nonlinear dynamics in sudden cardiac death syndrome: heartrate oscillations and bifurcations.

Patients at high risk of sudden cardiac death show evidence of nonlinear heartrate dynamics, including abrupt spectral changes (bifurcations) and sustained low frequency (.01–.04 Hz) oscillations in heartrate.

Conventional heart rate variability analysis of ambulatory electrocardiographiic recording fails to predict imminent ventricular fibrillation

OBJECTIVES The purpose of this report was to study heart rate variability in Holter recordings of patients who experienced ventricular fibrillation during the recording. BACKGROUND Decreased heart rate variability is recognized as a long-term predictor of overall and arrhythmic death after myocardial infarction. It was therefore postulated that heart rate variability would be lowest when measured immediately before ventricular fibrillation. METHODS Conventional indexes of heart rate variability were calculated from Holter recordings of 24 patients with structural heart disease who had ventricular fibrillation during monitoring. The control group consisted of 19 patients with coronary artery disease, of comparable age and left ventricular ejection fraction, who had nonsustained ventricular tachycardia but no ventricular fibrillation. RESULTS Heart rate variability did not differ between the two groups, and no consistent trends in heart rate variability were observed before ventricular fibrillation occurred. CONCLUSIONS Although conventional heart rate variability is an independent long-term predictor of adverse outcome after myocardial infarction, its clinical utility as a short-term predictor of life-threatening arrhythmias remains to be elucidated.

Increased Walking Variability in Elderly Persons with Congestive Heart Failure

OBJECTIVES: To determine the effects of congestive heart failure on a persons ability to walk at a steady pace while ambulating at a self‐determined rate.

Nonlinear Dynamics at the Bedside

Heart rhythms in health and disease display complex dynamics. The clinical data suggest that concepts developed in nonlinear mathematics, such as bifurcations and chaos, will be appropriate to describe some of these complex phenomena. Careful analysis will be needed to establish the presence of deterministic chaos in cardiac rhythms. Data that appear highly periodic such as normal sinus rhythm may in reality be quite variable. In contrast, chaotic-appearing rhythms such as ventricular fibrillation often contain strong periodicities.

A new technique for simultaneous monitoring of electrocardiogram and walking cadence

A new technique for simultaneously recording continuous electrocardiographic (ECG) data and walking step rate (cadence) is described. The ECG and gait signals are recorded on 2 channels of an ambulatory Holter monitor. Footfall is detected using ultrathin, force-sensitive foot switches and is frequency modulated. The footfall signal provides an indication of the subjects activity (walking or standing), as well as the instantaneous walking rate. Twenty-three young and elderly subjects were studied to demonstrate the use of this ECG and gait recorder. High-quality gait signals were obtained in all subjects, and the effects of walking on the electrocardiogram were assessed. Initial investigation revealed the following findings: (1) Although walking rates were similar in young and elderly subjects, the elderly had both decreased heart rate (HR) variability (p < 0.005) and increased cadence variability (p < 0.0001). (2) Overall, there was an inverse relation between HR and cadence variability (r = -0.73). Three elderly subjects with no known cardiac disease had HR and cadence variability similar to those of the young, whereas elderly subjects with history of congestive heart failure were among those with the lowest HR variability and the highest cadence variability. (3) Low-frequency (approximately equal to 0.1 Hz) HR oscillations (frequently observed during standing) persisted during walking in all young subjects. (4) In some subjects, both step rate and HR oscillated at the same low frequency (approximately equal to 0.1 Hz) previously identified with autonomic control of the baroreflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Downregulation of DNA topoisomerase I in old versus young human diploid fibroblasts

DNA topoisomerase I (Topo I) is an enzyme that alters the superhelicity of DNA. It has been implicated in such critical cellular functions as transcription, DNA replication, and recombination. Roles for Topo I in DNA repair following DNA damage have also been studied extensively. In the present investigation, we examined the regulation of Topo I expression and activity during cellular replicative senescence. We found that the capacity of Topo I to relax supercoiled DNA molecules is significantly decreased in senescent diploid fibroblasts when compared to young (early passage) fibroblasts. We also found that the steady-state expression level of Topo I mRNA is correlated with enzyme activity, i.e., decreased in early vs. late passage cells. We also treated early and late passage cells with agents that may modulate the process of cellular senescence: UV light, retinoic acid, and interleukin-1 beta. We found that all three agents decreased the activity of Topo I in young fibroblasts and increased the activity of Topo I in senescent fibroblasts. This effect was most striking following exposure of the cells to retinoic acid, so to analyze this effect, we postulated an age-dependent kinetics of Topo I mRNA induction in response to retinoic acid. Consistent with this postulate, we found that whereas exposure of early passage cells to retinoic acid results, in a matter of hours, in a decrease in the expression of Topo I mRNA, exposure of the senescent cells to retinoic acid results in an increased expression. These observations suggest that processes that are altered in senescent fibroblasts, such as DNA replication and repair, may be due, in part, to alteration in the expression and activity of DNA Topo I.

bpshape wk4: a computer program that implements a physiological model for analyzing the shape of blood pressure waveforms

We describe the theory and computer implementation of a newly-derived mathematical model for analyzing the shape of blood pressure waveforms. Input to the program consists of an ECG signal, plus a single continuous channel of peripheral blood pressure, which is often obtained invasively from an indwelling catheter during intensive-care monitoring or non-invasively from a tonometer. Output from the program includes a set of parameter estimates, made for every heart beat. Parameters of the model can be interpreted in terms of the capacitance of large arteries, the capacitance of peripheral arteries, the inertance of blood flow, the peripheral resistance, and arterial pressure due to basal vascular tone. Aortic flow due to contraction of the left ventricle is represented by a forcing function in the form of a descending ramp, the area under which represents the stroke volume. Differential equations describing the model are solved by the method of Laplace transforms, permitting rapid parameter estimation by the Levenberg-Marquardt algorithm. Parameter estimates and their confidence intervals are given in six examples, which are chosen to represent a variety of pressure waveforms that are observed during intensive-care monitoring. The examples demonstrate that some of the parameters may fluctuate markedly from beat to beat. Our program will find application in projects that are intended to correlate the details of the blood pressure waveform with other physiological variables, pathological conditions, and the effects of interventions.

On the non-linear motions of the heart: Fractals, chaos and cardiac dynamics

Publisher Summary This chapter discusses the nonlinear motions of the heart, namely, the fractals, chaos, and cardiac dynamics. It describes some applications of nonlinear dynamics to cardiac physiology and to cell-to-cell signaling in circulatory control. The fractal concept may be applied to understanding the mechanism of physiologic heart rate variability, that is to say, fluctuations in the beat to beat sinus node rate. Under physiologic conditions, the heart rate is regulated by the firing of the pacemaker cells in the sinus node. This sinus rhythm mechanism, in turn, is controlled by signals from the involuntary branch of the nervous system. The heart rate in healthy subjects at rest is not strictly regular or periodic. Instead, the heart rate in sinus rhythm fluctuates is an apparently erratic fashion with a time series representation consistent with chaos. The spectrum of this healthy variability is broadband, with a l/ f -like distribution. The nonlinear dynamics of the heart rate can be viewed as epiphenomenal as they are under the influence of neural control.

Note on the dispersion of generations among cells in senescing diploid fibroblast populations

The cells in a cultured diploid fibroblast population have heterogeneous intermitotic times--even cells derived from the same mitosis may divide at different ages. This heterogeneity of inter-mitotic times results in asynchronous population growth and a dispersion of generations among members of the cell population. Because the appearance of non-dividing cells in middle-age populations has been attributed to the presence of lineages with more generations than average, we estimated the magnitude of the dispersion of cell generations as functions of the population doubling level and of the coefficient of variation of inter-mitotic times. For some data, such as that of Macieira-Coelho and Azzarone (Exp. Cell Res., 141 (1982) 325, the rate at which such non-proliferating lineages appear could be explained by a reasonable coefficient of variation of inter-mitotic times (25%). Most other data, however, would be fit only if the coefficient of variation of inter-mitotic times were 50% or greater, a variability that exceeds what has been observed in microcinematography experiments.