SlideShare une entreprise Scribd logo
1  sur  10
Télécharger pour lire hors ligne
Medical Hypotheses (1998) 51, 367-376
© Harcourt Brace & Co. Ltd 1998




Fractal organization of the pointwise correlation
dimension of the heart rate
E. NAHSHONI, E. ADLER*, S. LANIADO*, G. KEREN*

Department E, The Gehah Psychiatric Hospital, Petah-Tiqva, and Sackler School of Medicine, Tel Aviv,
Israeb *Department of Cardiology, Tel Aviv Medical Center, Tel Aviv, and Sackler School of Medicine,
Tel Aviv, Israel. Correspondence to: E. Nahshoni, POB 102, 49100 Petah-Tiqva, Israel
(Phone: +972 3 9258258; Fax: + 972 3 9241041)


Abstract - - Objective: To depict and quantify the degree of organization of the heart rate
variability (HRV) in normal subjects. Methods: A modified algorithm was created to estimate
series of "point-dimensions" (PD2) from interbeat (R-R) interval series of 10 healthy subjects
(21-56 years). Our innovation is twofold: (i) we quantified instances of low-dimensional chaos,
random fluctuations, and those for which our method failed to provide either (due to poor
statistics); (ii) consecutive subepochs of PD2s underwent a relative dispersion (RD) analysis,
yielding an index (D) which quantifies the dynamical organization of the heart rate generator.
   Results: The mean values of PD2 series varied between 4.58 and 5.88 (mean +_SD=
5.21 +_0.41, n = 10). For group 1 (21-30 years, n = 6) we found an averaged PD2 of 5.49 _+0.27,
while for group 2 (47-56 years, n = 4) PD2 averaged 4.79 +_.0.17. The RD analysis performed
for subepochs of PD2s yielded both instances obeying fractal scaling (D < 1.5) and
stochasticity (D > 1.5). The average D for group 1 was 1.39 + 0.04 (14 subepochs) and for
group 2, 1.20 _+0.008 (8 subepochs). Paired t-test and Hartley F-max test for comparison
between D values and homogeneity of variance between the two groups were performed,
yielding P-values 0.004 and 0.02, respectively.
   Conclusions: The complexity of the HRV seems to be modulated by a non-random fractal
mechanism of a 'hyperchaotic' system, i.e. it can be hypothesized to contain more than one
attractor. Also, our results support the 'chaos hypothesis' put forth recently, namely, the
complexity of the cardiovascular dynamics is reduced with aging. The index of relative
dispersion of the dimensional complexity has to be tested in various clinico-pathological
settings, in order to corroborate its value as a potential new physiological measure.

Introduction                                              frequency and phases of biological oscillators, or to
                                                          the coupling of various regulatory feedback loops,
Physiological systems have long been recognized to        thus engaging nonlinear mechanisms for elucidation
display complex temporal fluctuations, even during        of the dynamics. Although, as in the physical sciences,
'steady state' conditions. Attempts were made to attri-   solutions have resulted in 'linearizations', only during
bute them to random influences, which perturb the         the last decade has a natural link been drawn between

Received 28 April 1997
Accepted 12 June 1997
                                                      367
368                                                                                              MEDICAL HYPOTHESES'


the mathematico-physical field of nonlinear dynamics         theses, which motivated ongoing research efforts
and physiology. This has triggered an ongoing trend          meant to quantify the dynamical characteristics of
of 'paradigm shift' in the medical sciences and in           the heart rate dynamics under the assumption that
biological thinking in general.                              it evolves on a low-dimensional 'strange attractor'.
   Since the advent of digital processing, the heart rate    These attempts were based mainly on dimensional
became the most accessible and reliable signal for           analysis, which resulted in correlation dimensions
analysis among cardiovascular variables. The heart           (interpreted as a static measure of the number of
rate variability (HRV) is traditionally assessed using       independent variables necessary to specify the state of
frequency (spectral analysis) and time (standard de-         the system under study), ranging between 3.6 and 5.2
viations, interval occurrence histograms, etc.) domain       in normal subjects (17). This was supported later, by
techniques. Using such techniques a complex coupling         introducing another measure of deterministic chaos,
with respiration, baroreceptors, the nervous system,         i.e. the largest Lyapunov exponent which yielded a
body temperature, metabolic rate, hormones, sleep            finite positive value, thus demonstrating the property
cycles, etc. was revealed. For example, spectral analysis,   of sensitivity to initial conditions, which is the hall-
which exposed activity bands in the frequency                mark of chaotic behavior (18). But later estimates
domain comprising thermoregulation (~0.05Hz),                of the correlation dimension were found to be much
baroreflex control of peripheral resistance (~ 0.1 Hz)       higher (-8.5) than previously reported, thus pre-
and respiratory control (~ 0.2 Hz), was combined             cluding firm conclusions as to the true nature of the
with pharmacological blockade to attribute the lower-        heart rate generator (19).
band fluctuations (0.04--0.15 Hz) to the joint influence        Recently, other modified measures of dynamical
of the sympathetic and parasympathetic arms of the           complexity, mostly suited for nonstationary, noisy,
autonomic nervous system, while the higher fre-              and limited record length signals, have been intro-
quency band (0.15-0.4 Hz) was shown to be purely             duced. Among them is the estimation of the pointwise
parasympathetically mediated. The spectral signature         correlation dimension (PD2), which provides more
of HRV was also related to various physiological             information about the temporo-spatial evolution of
and pathophysiological settings, such as standing,           the dominant complexity of the heartbeat (20,21).
hemorrhage and hypotension, which enhance the low            This technique was applied to a very limited number
frequency fluctuations, while exercise and standing          of subjects, from which no firm conclusions could
decrease the respiratory fluctuations. From the clinico-     be drawn, except for one clinical study which corre-
pathological viewpoint, patients with heart failure          lated a reduced dynamical complexity hours before
have diminished power spectrum at frequencies above          the occurrence of lethal arrhythmias in high-risk
~ 0.02 Hz (1-7). The other arm of traditional analysis,      patients (22).
the time domain analysis, has related decreased HRV             In the light of the open questions and computa-
in diabetes mellitus, ischemic heart disease, conges-        tional restrictions in this growing field of research,
tive heart failure (8), and also associated an increased     we addressed the issue of the irregular nature of the
mortality in patients after acute myocardial infarction      HRV in 10 healthy subjects. We computed correlation
(9).                                                         dimensions and the series of pointwise dimensions.
   Taken together, these techniques have several short-      We also introduced a modified version of the point-
comings. For example, spectral analysis is a method          wise dimension algorithm, which, we believe, can
mostly suited for linear systems, while physiological        depict both instances of low-dimensional chaos and
systems are inherently nonlinear. Also, time domain          stochasticity. The complex relation between them
analysis, which is basically an averaging technique,         was investigated using fractal techniques. The physio-
overlooks the dynamical nature. Thus, it appears that        logical and clinical importance of the measure we
these techniques are often insufficient to characterize      introduced is still unknown.
the complex behavior of the heart rate generator.
   Since the last decade, nonlinear methods of analysis,
based on the paradigm of deterministic chaos (10),           Methods
have permeated the realm of biomedical signal
analysis (11). This was motivated by the observation
                                                             Subjects
of an inverse power-law scaling (also called 1/f             Ten volunteers, aged 21-56 (6 males, 4 females)
spectrum), which some chaotic systems may display,           without symptoms or history of heart disease and
and by its association to the fractal concept (mani-         under no medication, were recruited for the study.
fested by self-similarity over multiple orders of            Their surface ECG, which showed no signs of patho-
temporal magnitude) (12-16). In the case of heart rate       logy, was recorded at rest in a supine position, during
dynamics, these observations heralded new hypo-              quite spontaneous breathing (~ 15 breaths/min) for
FRACTAL ORGANIZATION IN HEART RATE                                                                                369

20 rain. All recordings were done between 10 and              series were time-delayed for successive embedding
12 a.m., and each subject was allowed to adjust               dimensions (from m = 1 to m = 16). Within a given
comfortably for 10 min in a supine position before the        embedding dimension, the distance (r) of each point
data were collected. They all gave informed consent           to every other point was calculated. Their absolute
to the protocol.                                              values were rank-ordered from the smallest to the
                                                              largest, and the range from the smallest to the largest
Data aquisition                                               value was broken up into discrete intervals. Then, the
                                                              number of times a distance fell within an interval was
The ECG signals were continuously recorded using a            counted. A cumulative histogram was then formed
laptop-based HIPEC ANALIZER HA-200/AH system                  by summing the number of instances for which a
(Aerotel - - computerized systems, Israel) with a             distance was less than or equal to the upper boundary
sampling rate of 1000 Hz, and 16 bit signal resolu-           of the interval. This is the correlation integral C(r).
tion. The ECG records were transferred to a personal          C(r) was then plotted as a function of r on a log-log
computer for off-line analysis which started with a           representation, resulting in a sigmoid-shaped curve
quality control procedure: visual inspection, baseline        (in this case implying chaotic dynamics). The slope
shift evaluation and a 'moving average' (four points          over the largest linear range (if there is one) was
averaging in succession along the record) for signal to       measured, using linear regression (with a regression
noise ratio improvement. Then the interbeat intervals         coefficient R 2 > 0.98). In this scaling range the local
(R-R) were computed using an algorithm developed              exponent is constant and ~ d InC(r)/d In(r). Then, the
in our laboratory, with which an R wave threshold             embedding dimension was advanced and its corre-
detection was combined with first derivative and QRS          sponding slope was calculated. These slopes were
width considerations, for an accurate R wave detection.       then plotted versus the embedding dimension, looking
                                                              for a saturation region, i.e. a region in which the
Attractor reconstruction                                      slopes no longer grow. This plateau region was then
Usually the experimentalist is confronted with in-            considered as the correlation dimension (D2), and its
ability to gain access to m simultaneous recordings           value was calculated with a weighted average tech-
necessary to describe the system's trajectory in              nique (each value in the plateau region was weighted
m-dimensional phase space. Thus, only one scalar              by the variance of its underlying slope calculation).
observable can be monitored as a function of time.            This process was also performed for randomized
Fortunately, it has been shown that certain properties        versions of the R - R series (with similar mean and
of the dynamics are feasible through the method of            variance) in order to provide confidence limits for our
time delays using Taken's theorem, as follows (23).           calculations.
Consider a single time series regularly spaced in
time: xi = x%), i = 1..... N. Then a time lag "~is intro-     Pointwise dimension of R-R intervals
duced, such that m-dimensional vectors are created:
xi= [x(ti), x(ti + "c)..... x(ti+ (m-1)x)]. This process is   The 'point' estimate of the correlation dimension
termed embedding, and m is called the embedding               (PD2) begins with the time lag calculation, followed
dimension. Through this reconstruction a phase                by the embedding procedure, as described before.
space is spanned and dynamical and metric measures            Then, starting with the initial point in the series, its
(Lyapunov exponents, dimensions) may be accessible.           local correlation integral is calculated, i.e. the dis-
                                                              tances are taken with respect to this point and ranked-
                                                              ordered as usual, for each embedding dimension
Correlation dimension of R-R intervals
                                                              (m = 1..... 16). The slopes for each m were evaluated
The correlation dimension was calculated using the            using a linear regression (R2> 0.98), and a slope
method of Grassberger and Procaccia (G-P) as follows          values, corresponding to m = 8 ..... 16 were stored in
(24). First, for each R - R interval series, the normal-      a file. The algorithm steps to the next point in the
ized autocorrelation function given by:                       series, and the whole procedure is repeated until the
                                                              whole file is exhausted. Then comes the procedure
~g('~) = {(I/N) £[R-R)i - < (R-R) >][(R-R)i+x -
                                                              that we call slope convergence, which calculates the
         < (R-R) >] }/{(I/N) Z[R-R)i - < (R-R) >]2}
                                                              slope of the 9 slopes versus the embedding dimensions
where                                                         (m = 8 ..... 16) using linear regression. Our innova-
                                                              tion was to subject this to the imposition of three
< (R-R) > = (l/N) Z (R-R)/
                                                              conditions as follows: Ill if the slope was less than
was constructed, and its first zero crossing was calcu-       0.5 and larger than -0.23, we considered this as good
lated to provide the time lag (x) in beats. Then, the         convergence and the PD2 could be estimated using
370                                                                                                  MEDICAL HYPOTHESES


the weighted average technique as described before;         dimensions was needed. Homogeneity of variance
(ii) if the slope was equal or larger than 0.5, we          was tested by the Hartley F-max test. Statistical
considered it as if no saturation existed, and at           significance was assumed if the null hypothesis could
this point (or time), the system probably manifested        be rejected at the 0.05 probability level.
a random fluctuation. In order to incorporate such
a behavior into the sequence of PD2s, we decided,
quite arbitrarily, to take the average of the two highest   Results
slope estimates, as the point-dimension, when such
a condition appears; (iii) if the slope was equal to        Thc correlation dimension (D2) of R-R intervals
or less than --0.23, we considered it as if no slope        varied from 3.29 to 5.16, with an overall mean of
convergence existed, and the dimensional estimate           4.01 ± 0.54 (Table 1). Fig. la illustrates one of the
at this point was excluded, possibly because of poor        series of R-R intervals. This corresponding normal-
statistics.                                                 ized autocorrelation function is shown in Fig. lb. The
   The results of the PD2 series were 'assigned'            first zero crossing (x), in this case was equal to 6
according to the three conditions mentioned above.          beats. The correlation integral (C(r)) for embedding
This provided us with the ability to discriminate the       dimensions (m = 2,4,6,9,12,16) is shown in Fig. 2a,
points which manifested low-dimensional chaos and           while the calculated slopes in the linear regions of
random behavior, from those for which a dimensional         the log-C(r) representation, versus the embedding
estimate could not be achieved. From the above              dimension, is shown in Fig. 2b. Note the convergence
output files we extracted sequences of dimensional          towards a dimensional value of 4. Randomized ver-
subepochs, which were then suited for the relative          sions of the R-R intervals have demonstrated, as
dispersion analysis.                                        expected, non-convergence (Fig. 2c).
                                                               A sequence of pointwise dimensions (PD2s) versus
                                                            the reference point is shown in Fig. 3a. Note three
Dispersion analysis                                         regions in the dimensional complexity plot, i.e. high
                                                            values (PD2 > 6), low-dimensional region (3 > PD2 < 6)
There are three basic methods of dispersion analysis
                                                            and zero-valued reference points, corresponding to
that can be applied to temporal observations (25). One
                                                            non-convergence due to poor statistics. This can be
of them, adopted in our study for each sequence of
                                                            seen from the histogram (Fig. 3b) showing the distrib-
calculated pointwise dimensions, is called relative
                                                            ution of the rounded dimensional values, including
dispersion (RD) analysis. Our intention was to try and
                                                            the points corresponding to stochasticity and to non-
see if the temporal evolution of PD2 series obeys any
                                                            calculability at both ends of the figure. For the subject
scaling properties. Thus for each subject, this simple
                                                            shown in the figure the average PD2 was 5.37 ± 0.93.
algorithm goes as follows: first, the mean, standard
                                                            In Fig. 4, four subepochs, each comprising ~150 PD2
deviation (SD), and RD% (= 100 x SD/mean) of the
                                                            values (corresponding to an average of about 2.5
original PD2 series were calculated. Then, pairs of
                                                            minutes'-record-length each) are shown. In Fig. 5 the
adjacent PD2s were averaged and their RD% values
                                                            logarithmic plot of the RD(%) versus the interval
were calculated, thus doubling the interval length.
Recursive pairing with doubling of each previous
interval length was carried out while its correspond-
                                                            Table 1 Correlation dimension (D2) of 10 healthy
ing RD% was calculated. This was done until the             subjects at rest
whole record was exhausted. By plotting the RD%
against the interval length on a logarithmic scale, the     Gender      Age (years)   HR ± SD       Correlation dimension
slope was estimated using a least-squares linear fit.                                 (beat/rain)   (D2 ± ZkD2)
The fractal dimension (D) could thus be extracted
from the slope (slope --- l-D). In order to confirm the     M           21            69.1 ± 5.6    4.51 ± 0.13
temporal organization of the PD2 series, randomized         F           25            65.5 ± 3.0    3.58± 0.07
versions based on similar statistical characteristics       M           26            65.2 ± 2.5    3.93 ± 0.09
                                                            F           28            67.6± 3.5     5.16 ± 0.02
(number of points, mean and standard deviation) were        M           30            57.6 ± 4.6    3.99 ± 0.16
generated, and their RD analysis was also performed.        M           30            54.2±2.3      4.50±0.19
                                                            M           47            71.4± 3.9     3.87 ± 0.21
                                                            M           56            60.9 ± 3.0    3.29 ± 0.19
                                                            F           56            64.7 ± 2.3    3.48 ± 0.21
Statistical analysis
                                                            F           56            66.8 ± 2.6    3.77 ± 0.03
All data are expressed as mean ± SD. A paired t-test        mean ± SD   37.5 ± 13.7   64.3 ± 5.0    4.01 ± 0.54
was performed when comparison between fractal
FRACTALORGANIZA~ONINHEARTRATE                                                                                                  371

                     1.25




                     0.75


                e-
             •-       0.5-
              I
             e¢-


                     0.25



                        0
                             1                                500                                    1000
                                                                Beat number

                      0.7

                      0.6

                      0.5

                      0.4--

                      0.3--

                      0.2

                      0.1-

                        0

                     -0.1                                    .'v                   ,   ,    ....   'IW ,v,' ' V V_
                     -0.2                                                                                                 m



                                                        100                                200                           300
            b                                                             T
            Fig. 1 (a) R - R intervals for one of the subjects (1296 intervals, 20 min). (b) The normalized
            autocorrelation function of R - R intervals shown in (a). The first zero crossing was found to be 6 beats.



length (measured in beat number) for one of the                     850. The overall mean values of the PD2 series varied
subepochs is shown. Its slope provides the fractal                  between 4.5 and 5.88 (mean = 5.21 ± 0.41, n = 10),
dimension of the dimensional complexity at a parti-                 but the mean PD2s of the various subepochs were
cular subepoch.                                                     smaller than the overall average, at least during one
   Table 2 summarizes the results of the fractal                    subepoch for each subject. We divided the subjects
dimensions (D) of the subepochs of series of PD2s.                  into two groups according to their age. For group 1
The shortest subepoch consisted of 80 consecutive                   (21-30 years) the average PD2 varied between 5.19
dimensional values, while the longest consisted of                  and 5.88 (mean = 5.49 ± 0.27, n = 6), while the
372                                                                                                                                                                                              MEDICAL HYPOTHESES


                                                    0

                                                -1,

                                                -2.

                                                -3
                                       to
                                       t-       -4

                                                -5

                                                -6


                                                -7                                        1'5                '     '   2~0 . . . .                   2~5 . . . .
                                                                                                                       Inr


                                                                                                     Emb 9       --K--- Emb 12 ~        Emb 16



      5                                                                                                                             8
C                                                                                                                              C
0                                                                                                                              O
r
 r   4                                                                                                                         r
?                                                                                                                              ?6
 i   3                                          .                                                                              i
0                                                                                                                              O
n                                                                                                                              n    4

d
i
      2                                                                                                                        ?
m                                                                                                                              m
e                                                                                                                              e    2
n     1                                                                                                                        [I


0                                                                                                                              O
n    0                                                                                                                         n
          .   .       .       .    .    .       .       .       .   .   .    .        .    .                                        0    .   .       .   .   .       .    .   .               110 111    I    i    I4    I
          2       3       4       5         6       7       8       9   10       11       12    13   14   15      16                     2       3       4       5       6        7   8   9             1    13   1     1    16
 b                                Embedding dimension                                                                         c                                  Embedding dimension
Fig. 2 The correlation integral C(r) versus r on a logarithmicplot. Seen are embeddingdimensions m = 2, 4, 6, 9, 12, 16. (b) The slope
of the scaling region as a function of the embeddingdimension (m), for a healthy subject (26 years). Note the saturation towards a
correlation dimension (D2) estimate of ~4. (c) For a randomlygenerated version of R-R intervals, the slope estimates of In C(r) versus
lnr, as a functionof the embeddingdimension, do not saturate.




relative dispersion analysis of their consecutive PD2                                                                        Discussion
series yielded both instances of fractal scaling
(D < 1.5) and stochasticity (D > 1.5). The averaged                                                                          The concept of fractals, first coined by B. Mandelbrot
fractal dimension for this group was 1.39 4-0.04                                                                             (26), and its association with chaos theory, heralded
(14 subepochs). In group 2 (47-56 years), the PD2                                                                            novel insights into the realm of structural and
mean values ranged between 4.58 and 5.03 (mean =                                                                             dynamical variability in the medical sciences (27)
4.79 ± 0.17, n = 4). Note that in group 2 the fractal                                                                        and biology in general (11). During the last decade,
estimates ranged between 1.09 and 1.33 (mean =                                                                               the intimate connection between deterministic chaos
1.20 ± 0.008, 8 subepochs), i.e. never exceeded 1.5.                                                                         and fractal geometry has stimulated ongoing research
   The t-test and the F-test showed statistical signi-                                                                       efforts to quantify the dynamical aspects of the heart
ficance when the means and variances of the fractal                                                                          rate generator. Babloyantz and Destexhe were the first
dimensions of the PD2 subepochs were compared                                                                                to quantify its dynamical measures using chaos theory
(P values: 0.004 and 0.02, respectively). Note that the                                                                      techniques (17). Their results (correlation dimensions,
overall results of the RD analysis were indicative                                                                           Kolmogorov entropies and the largest Lyapunov
of fractal scaling (D < 1.5) in about 80% of all                                                                             exponent), were supportive to the contention that the
subepochs tested.                                                                                                            heart rate generator evolves on a low-dimensional
FRACTAL ORGANIZATION IN HEART RATE                                                                                                  373

 10




                                               I                N of points
                                                                round(D2)-
                                                                                alp-)0.50
                                                                               0 N o! p-
                                                                                               4z m
                                                                                                0
                |                                               round(O2)-     I N of p-        0
                                               i
            I                                                   round(D2}-
                                                                round(D2)-
                                                                               2 H o f p-
                                                                            3 H of
                                                                rouncl(D2)m 4 N o f
                                                                roun4(D2)- S N of
                                                                roarl4(D2)- 6 N o f
                                                                                         p-
                                                                                         pm 246
                                                                                         p- Se2
                                                                                         pm 146
                                                                                                0



                                                                                               "k
                                                                roun4(D2)- 7 X o f       p - 64
                                                                round(D2)- 8 g of        p,,  ].
                                                                round(D2)- 9 N o f     p-       0
                                                                round(D2)-20      N of p-       0




            i
                                                                roun4(D2)-22      N of p-       0
                                                                round(D2)-12      N of p-       0
                                                                round(D2)-13      N of p-       0
                                                                round(D2)-14      N of   p-     0
                                                                round(D2)-25      N of   p-     0
                                                                round(D2)-26      H of   p"     0
                                                                round(D2)-17      N of   p,,    0
                                                                round(D2)-28      N of   p-     0
                                                                round(D2)-lg      N Of   p-     0
                                                                round(D2)-20      N of   p-     @
                                                                H of   exclu    sip<-0.23      2v •


  a


      0     250       500        750       1000       1250
Fig. 3 (a) Serial pointwise dimensions (PD2s) as a function of the beat number (nref) for one of the subjects. The zero-valued PD2s are
only 'sign' of the instances for which a dimensional estimate could not be derived. (b) A histogram showing the distribution of the beat
number as a function of the rounded dimensional estimates. At the two extremes of the diagram we note the number of points for which a
random fluctuation is supposed to take place (slope > 0.5), and on the other side the number of point for which an estimate could not be
found (slope < -0.23).



chaotic attractor. Later, other groups provided sup-                   periodic behavior was seen in normal subjects, with
portive evidence to this hypothesis (18,28), although                  an increase in complexity during sleep (21). Recent
recently Kanters et al found weak evidence in favor                    studies found the dimensional complexity during
(19). Thus, the existence of low dimensional chaos in                  experimental myocardial infarction in pigs to decline
cardiac activity, at least at the whole organ level of                 significantly prior to the occurrence of ventricular
activity, is still an open question. Most of the estima-               fibrillation (31). This has motivated Skinner et al
tions were based on dimensional estimations of the                     to evaluate lethal arryhythmias in various groups of
widely used Grassbeger-Procaccia algorithm. Imple-                     high-risk patients. It was found (with high specificity
mentation of this algorithm needs several precondi-                    and sensitivity) that the dimensional complexity
tions to be observed (29,30): an adequate choice of                    is reduced hours before the occurrence of lethal
embedding dimension, a suitable choice of the time                     arrhythmias (22).
delay needed to span the attractor, low level of noise                    Our results support the contention of low-
present in the system, stationarity, and the data set                  dimensional chaos, as proposed by others. The corre-
should not be too short. Some of these requirements                    lation dimension was found to vary between 3.29
are not attainable in biology and in physiology in                     and 5.16, with a mean of 4.01 + 0.54 (n = 10). The
particular. Moreover, the G-P algorithm provides a                     average pointwise dimension ranged between 4.58
dimensional estimate which averages out possible                       and 5.88, with a mean of 5.21 + 0.41 (n = 10). Further-
relevant dynamical features. Recently, the intro-                      more, we noticed that our subjects could be divided
duction of the pointwise dimension algorithm, which                    into two groups according to age as follows: group 1
provides series of 'point' dimensions, has provided                    (21-30) years, n = 6) had a higher average, 5.49 + 0.27,
some solutions to the limitations of the G-P algo-                     than group 2 (47-56 years, n = 4 ) at 4.79+ 0.17.
rithm, namely, non-stationarity and record length.                     Our innovation in this study was twofold. First, we
This method was implemented for heart transplant                       included in the dimensional complexity algorithm
recipients and the dimensional complexity was found                    means to include both instances of low-dimensional
to oscillate almost periodically (20). Also, a roughly                 chaos and stochastic bursts in a sequential manner,
374                                                                                                        MEDICAL HYPOTHESES


        10                                                         2O




                                                                     g
                                                                                 tJL,           JJl|
                                                                                                     RF'
                                                                                                        Jd l


        I0                                                          10




              i1.                                                    D   ill
                                                                         I'r
                                                                                                           ,I



        Fig. 4 Four subepochs of sequential PD2s from the series shown in Fig. 3a. Each subepoch comprises about
        150 PD2s.



i.e. as a function of the beat number. Second, this              cant decline in the complexity of the cardiovascular
enabled us to apply a fractal technique (relative                system (blood pressure and heart rate). Such findings
dispersion analysis) to explore the different subepochs          may reflect the breakdown and decoupling of inte-
of dimension series for scale independence. We found             grated physiologic regulatory systems with aging
that the older group manifested fractal scaling                  and may signal an impairment in the cardiovascular
(D < 1.5) in all subepochs tested. As for the younger            ability to adapt efficiently to internal and external
group, only in 64% of tested subepochs did we find               perturbations. This is contradictory to the sacred
fractal scaling (D < 1.5), while the rest was indicative         principle of 'homeostasis', which was developed by
of a random control (D > 1.5). Moreover, the differ-             Walter Cannon, and postulates that with disease and
ences in the averages and variances of the fractal               aging the body is less able to maintain a constant
dimensions between the two groups were found to                  steady state, as a result of breakdown of its regulatory
be statistically significant. This is in contention with         systems. Our findings support the chaos hypothesis of
results from other chaos-derived techniques imple-               a 'homeokinetic' principle in physiology, namely,
mented by Kaplan et al on old versus young subjects              physiological systems in young healthy subjects tend
(32). They found that the older group showed signifi-            to fluctuate between a set of metastable states, thus
FRACTAL ORGANIZATIONIN HEART RATE                                                                                                 375

                                                                     of the heart rate variability, which can be quantified
    20                                                               using fractal techniques, seems to contain 'mixing' of
                                                                     both chaotic and random fluctuations. The nature
    10
                                                                     of such a behavior is not yet understood, but one
     5
                                                                     may hypothesize that an increase in the dimensional
                                                                     complexity (D2 can be thought of as a measure
                                      --,..                          of independent variables necessary to describe the
    2


                                                
                                                                     system), may correspond to recruitment of several
     1                                                               subsystems influencing the heart rate generator, or
                                                                     to the activation of more independent control loops.
0.50                                                                 A reduced complexity, on the other hand, may mani-

0.20
                                                                    fest deactivation of control loops, or maybe increased
                                                                     self-organization of some of these systems. Also, the
                                                                     abrupt changes in the dimensional complexity may
0.10                                                                 represent shifts between different attractors of the
                                                                     system. Such hypotheses, may better be resolved by
    140     74      37      19      10          5        3
                                                                     comparing the fractal dimensions of the dimensional
Fig. 5 Plot of RD% (relative dispersion) versus interval length on
                                                                     complexity (and other measures of nonlinear tech-
a logarithmic scale. The fractal dimension (D) is derived from the   niques) under different physiological and clinico-
slope (slope = l-D).                                                 pathological settings.
                                                                        Currently, we are in the process of obtaining longer
                                                                     data records from heart transplant recipients, in order
making the system more adaptable to its internal and                 to gain more insight regarding the value of the fractal
external surroundings (15,33).                                       estimate of the dimensional complexity of the heart
  We thus propose that the dimensional complexity                    rate generator, as a potential new dynamical measure.



T a b l e 2 Subepochs o f pointwise dimension (PD2) series, averaged P D 2 s for each subepoch, fractal dimension (D) for
each subepoch, and averaged P D 2 s for w h o l e records

Gender       Age         Nref            PD2 ± SD average over subepochs        D(RD) ± SD        PD2 ± SD average over total record

M            21            1-150         5.28   ± 0.88                          1.42 + 0.07       5.37 ± 0.93
                         300--450        5.09   ± 0.09                          1.27 + 0.03
                         570-720         5.61   ± 0.73                          1.49 ± 0.06
                         850-1000        4.35   ± 0.69                          1.09 ± 0.04
F            25            1-90          4.45   ± 1.05                          1.21 ± 0.09       5.19 ± 1.04
                         200-350         4.86   + 0.75                          1.54 ± 0.06
M            26          130-196         6.01   ± 0.97                          1.72 ± 0.11       5.83 ± 1.02
                         250-850         5.62   ± 0.97                          1.19 ± 0.10
F            28            1-300         5.90   ± 0.90                          L28 + 0.09        5.34 ± 0.72
                         301--600        5.03   ± 0.35                          1.36 ± 0.12
M            30            1-200         4.91   ± 0.69                          1.55 ± 0.09       5.30 ± 0.11
                         600--995        5.09   ± 1.10                          1.13 ± 0.06
M            30          30-110          5.92   ± 0.83                          1.57 ± 0.09       5.88 ± 1.08
                         125-295         5.34   ± 0.82                          1.63 ± 0.09
M            47            1-350         3.92   ± 0.51                          1.11 ± 0.04       4.69 ± 0,77
                         400-1250        4.99   ± 0,63                          1.21 ± 0.06
M            56            1-300         4.95   ± 0,68                          1.18 ± 0.07       5.03 ± 0,71
                         500-1000        5.11   ± 0.69                          1.32 ± 0.05
F            56          100-300         4.63   ± 0.72                          1.24 ± 0.07       4.87 ± 0.96
                         500-750         4.32   ± 1.21                          1.09 ± 0.05
F            56            1-80          4.39   ± 0.69                          1.33 ± 0.08       4.58 ± 0.64
                         200-380         4.63   ± 0.79                          1.14 ± 0.08
mean ± SD                                5.02 ± 0.54                            1.32 ± 0.18        5.21 ± 0.41

M, male; F, female; Nref, sequences of consecutive data points' subepochs; PD2 + SD, averaged pointwise dimension + standard deviation;
D(RD), fractal dimension of each subepoch, derived from relative dispersion analysis.
376                                                                                                                 MEDICAL HYPOTHESES


References                                                              15. Lipsitz L A. Age-related changes in the 'complexity' of
                                                                            cardiovascular dynamics: a potential marker of vulnerability to
 1. Appel M L, Berger R D, Saul J P, Smith J M, Cohen R J. Beat             disease. Chaos 1995; 5(1): 102-109.
    to beat variability in cardiovascular variables: noise or music?    16. Kobayashi M, Musha T. 1/f fluctuation of heartbeat period.
    J Am Coil Cardiol 1989; 14:1139-1148.                                   IEEE Trans Biomed Eng 1982; 29: 456-457.
 2. Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular         17. Babloyantz A, Destexhe A. Is the normal heart a periodic
    neural regulation explored in the frequency domain. Circula-            oscillator. Biol Cybernetics 1988; 58:203-211.
    tion 1992; 84: 482-492.                                             18. Rigney D R, Mielus J E, Goldberger A L. Is normal sinus
 3. Malliani A, Pagani M, Lombardi F. Physiology and clinical               rhythm 'chaotic'? measurement of Lyapunov exponents.
    implications of variability of cardiovascular parameters with           Circulation 1990; 82(4) Suppl. III, abstr.
    focus on heart rate and blood pressure. Am J Cardiol 1994;          19. Kanters J K, Holstein-Rathlou N-H, Agner E. Lack of
    73: 3C-9C.                                                              evidence for low-dimensional chaos in heart rate variability.
 4. Akselrod S, Gordon D, Ubel F A, Shannon D C, Barger A C,                J Cardiovasc Electrophysiol 1994; 5: 591-601.
    Cohen R J. Power spectrum analysis of heart rate fluctuations:      20. Zbilut J P, Mayer-Kress G, Giest K. Dimensional analysis of
    a quantitative probe of beat-to-beat cardiovascular control.            heart rate transplant recipients. Math Biosci 1988; 90: 40-70.
    Science 1981; 213: 220-222.                                         21. Mayer-Kress G, Yates F E, Benton L et al. Dimensional
 5. Saul J P, Arai Y, Breger R D, Lilly L S, Colucci W S, Cohen             analysis of nonlinear oscillations in brain, heart, and muscle.
    R J. Assessment of autonomic regulation in chronic congestive           Math Biosci 1988; 90: 155-182.
    heart failure by heart rate spectral analysis. Am J Cardiol 1988;   22. Skinner J E, Pratt C M, Vybrial T. A reduction in the correla-
    61: 1292-1299.                                                          tion dimension heartbeat intervals precedes imminent ventricular
 6. Pomeranz B, Macaulay R J B, Caudill M A e t al. Assessment              fibrillation in human subjects. Am Heart J 1993; 125: 731-743.
    of autonomic function in humans by heart rate spectral              23. Rand D, Young L-S, eds. Detecting strange attractors in fluid
    analysis. Am J Physiol 1985; 248 (Heart Circ Physiol 17):               turbulence. In: Dynamical Systems and Turbulence. Berlin:
    H151-H153.                                                              Springer-Verlag, 1981.
 7. Madwed J B, Snads K E F, Saul J P, Cojen R J. Spectral              24. Grassberger P, Procaccia I. Measuring the strangeness of
    analysis of beat-to-beat variability in HR and ABP during               strange attractors. Physica 1983; 9D: 183-208.
    hemorrhage and aortic constriction. In: Lown B, Malliani A,         25. Glenny R W, Robertson H T, Yamashiro S, Bassinghwaighte.
    Prodocimi M, eds. Neural Mechanisms and Cardiovascular                  Applications of fractal analysis to physiology. J Appl Physiol
    Disease. Fidia Research Series. Padova: Liviana Press, 1986,            1991; 70(6): 2351-2367.
    Vol. 5: 291-301.                                                    26. Mandelbrot B B. Thc Fractal Geometry of Nature. San
 8. Takase B, Kurita A, Noritake Met al. Heart rate variability in          Francisco: W H Freeman, 1982.
    patients with diabetes mellitus, ischemic heart disease, and        27. West B J. Fractal Physiology and Chaos in Medicine. New
    congestive heart failure. J Electrocardiol 1992; 25: 79-88.             Jersey: World Scientific, 1990.
 9. Kleiger R E, Miller J P, Bigger J T, Moss A J, and the Multi-       28. Ravelli F, Andolini R. Complex dynamics underlying the
    center Post-infarction Research Group. Decreased heart rate             human electrocardiogram. Biol Cyb 1992: 67; 57.
    variability and its association with increased mortality after      29. Kantz H, Schreiber T. Dimension estimates and physiological
    acute myocardial infarction. Am J Cardiol 1987; 59: 256-262.            data. Chaos 1995; 5(1): 143-154.
10. Ott E. Chaos in Dynamical Systems. Cambridge: Cambridge             30. Schreiber T, Kantz H. Noise in chaotic data: diagnosis and
    University Press, 1993.                                                 treatment. Chaos 1995; 5(1): 133-142.
11. Olsen L F, Degn H. Chaos in biological systems. Quarterly           31. Skinner J E, Carpeggiani C, Landisman C E, Fulton K W.
    Rev Biophys 1985; 10(2): 165-221.                                       Correlation dimension of hcartbeat intervals is reduced in
12. Goldberger A L, Rigney D R, West B J. Chaos and fractals                conscious pigs by myocardial ischemia. Circulation Res 1991;
    in human physiology. Sci Am 1990; 262: 42--49.                          68: 966-976.
13. Goldberger A L, West B J. Fractals in physiology and                32. Kaplan D T, Furman M 1, Pincus S M, Ryan S M, Lipsitz L A.
    medicine. Yale J Biol Med 1987; 60: 421-435.                            Aging and the complexity of cardiovascular dynamics. Bioph
14. Goldberger A L. Nonlinear dynamics, fractals and chaos:                 J 1991; 59: 945-949.
    applications to cardiac electrophysiology. Ann Biomed Eng           33. Lipsitz L A, Goldberger A L. Loss of 'complexity' and aging.
    1990; 18: 195-198.                                                      J Am Med Assoc 1992; 267: 1806-1809.

Contenu connexe

Tendances

Identification of wave free period in the cardiac cycle
Identification of wave free period in the cardiac cycleIdentification of wave free period in the cardiac cycle
Identification of wave free period in the cardiac cycleRamachandra Barik
 
Cardiac resynchronization therapy
Cardiac resynchronization therapyCardiac resynchronization therapy
Cardiac resynchronization therapyJose Osorio
 
Impact-of-weight-reduction-on-pericardial-adipose-tissue-and-cardiac-structur...
Impact-of-weight-reduction-on-pericardial-adipose-tissue-and-cardiac-structur...Impact-of-weight-reduction-on-pericardial-adipose-tissue-and-cardiac-structur...
Impact-of-weight-reduction-on-pericardial-adipose-tissue-and-cardiac-structur...Hany Abed
 
STICH (Surgical Treatment for Ischemic Heart Failure)
STICH (Surgical Treatment for Ischemic Heart Failure)STICH (Surgical Treatment for Ischemic Heart Failure)
STICH (Surgical Treatment for Ischemic Heart Failure)theheart.org
 
d35da723d00a4ad2991889a5c714a59b7d8a
d35da723d00a4ad2991889a5c714a59b7d8ad35da723d00a4ad2991889a5c714a59b7d8a
d35da723d00a4ad2991889a5c714a59b7d8aMarie Séveno
 
Critical appraisal of Stitch Trial by Dr. Akshay Mehta
Critical appraisal of Stitch Trial by Dr. Akshay MehtaCritical appraisal of Stitch Trial by Dr. Akshay Mehta
Critical appraisal of Stitch Trial by Dr. Akshay Mehtacardiositeindia
 
Stitch trial
Stitch trialStitch trial
Stitch trialauriom
 
Imaging techniques for myocardial hibernation
Imaging techniques for myocardial hibernationImaging techniques for myocardial hibernation
Imaging techniques for myocardial hibernationMichael Katz
 
Adressing Radial Artery Spasm
Adressing Radial Artery SpasmAdressing Radial Artery Spasm
Adressing Radial Artery SpasmDya Andryan
 
Myocardial viability
Myocardial viability  Myocardial viability
Myocardial viability Prithvi Puwar
 
Updates of CRT guidelines How do We Screen CRT Candidates?
Updates of CRT guidelines How do We Screen CRT Candidates?Updates of CRT guidelines How do We Screen CRT Candidates?
Updates of CRT guidelines How do We Screen CRT Candidates?Taiwan Heart Rhythm Society
 

Tendances (18)

Identification of wave free period in the cardiac cycle
Identification of wave free period in the cardiac cycleIdentification of wave free period in the cardiac cycle
Identification of wave free period in the cardiac cycle
 
Crt
CrtCrt
Crt
 
PDA size matters
PDA size mattersPDA size matters
PDA size matters
 
Cardiac resynchronization therapy
Cardiac resynchronization therapyCardiac resynchronization therapy
Cardiac resynchronization therapy
 
Role of CRT and CRTD in CHF
Role of CRT and CRTD in CHFRole of CRT and CRTD in CHF
Role of CRT and CRTD in CHF
 
Impact-of-weight-reduction-on-pericardial-adipose-tissue-and-cardiac-structur...
Impact-of-weight-reduction-on-pericardial-adipose-tissue-and-cardiac-structur...Impact-of-weight-reduction-on-pericardial-adipose-tissue-and-cardiac-structur...
Impact-of-weight-reduction-on-pericardial-adipose-tissue-and-cardiac-structur...
 
Toast criteria
Toast criteriaToast criteria
Toast criteria
 
STICH (Surgical Treatment for Ischemic Heart Failure)
STICH (Surgical Treatment for Ischemic Heart Failure)STICH (Surgical Treatment for Ischemic Heart Failure)
STICH (Surgical Treatment for Ischemic Heart Failure)
 
d35da723d00a4ad2991889a5c714a59b7d8a
d35da723d00a4ad2991889a5c714a59b7d8ad35da723d00a4ad2991889a5c714a59b7d8a
d35da723d00a4ad2991889a5c714a59b7d8a
 
Critical appraisal of Stitch Trial by Dr. Akshay Mehta
Critical appraisal of Stitch Trial by Dr. Akshay MehtaCritical appraisal of Stitch Trial by Dr. Akshay Mehta
Critical appraisal of Stitch Trial by Dr. Akshay Mehta
 
J r echo
J r echo J r echo
J r echo
 
Stitch trial
Stitch trialStitch trial
Stitch trial
 
Imaging techniques for myocardial hibernation
Imaging techniques for myocardial hibernationImaging techniques for myocardial hibernation
Imaging techniques for myocardial hibernation
 
Adressing Radial Artery Spasm
Adressing Radial Artery SpasmAdressing Radial Artery Spasm
Adressing Radial Artery Spasm
 
Triple low
Triple lowTriple low
Triple low
 
Myocardial viability
Myocardial viability  Myocardial viability
Myocardial viability
 
Updates of CRT guidelines How do We Screen CRT Candidates?
Updates of CRT guidelines How do We Screen CRT Candidates?Updates of CRT guidelines How do We Screen CRT Candidates?
Updates of CRT guidelines How do We Screen CRT Candidates?
 
Scientific news march 2015 samir rafla
Scientific news march 2015 samir raflaScientific news march 2015 samir rafla
Scientific news march 2015 samir rafla
 

En vedette

Maialen
MaialenMaialen
Maialengazadi
 
71071733[1]
71071733[1]71071733[1]
71071733[1]Al Maks
 
Overview of haggai zechariah and malachi
Overview of haggai zechariah and malachiOverview of haggai zechariah and malachi
Overview of haggai zechariah and malachiEdward Bryant
 
JH G321 Draft and layout for all construction parts
JH G321 Draft and layout for all construction partsJH G321 Draft and layout for all construction parts
JH G321 Draft and layout for all construction partsnctcmedia12
 
Evaluation Question 2
Evaluation Question 2Evaluation Question 2
Evaluation Question 2rturner93
 
Informe general
Informe generalInforme general
Informe generalkode99
 
ツイートするだけクライアント
ツイートするだけクライアントツイートするだけクライアント
ツイートするだけクライアント森理 麟
 
God's generous grace and our vocations
God's generous grace and our vocationsGod's generous grace and our vocations
God's generous grace and our vocationsEdward Bryant
 
Qc runtime parameters_for_qtp_tests
Qc runtime parameters_for_qtp_testsQc runtime parameters_for_qtp_tests
Qc runtime parameters_for_qtp_testsSandeep
 
การพัฒนามนุษย์และสังคมเพื่อความเป็นไท ความหมาย
การพัฒนามนุษย์และสังคมเพื่อความเป็นไท ความหมายการพัฒนามนุษย์และสังคมเพื่อความเป็นไท ความหมาย
การพัฒนามนุษย์และสังคมเพื่อความเป็นไท ความหมายSomprasong friend Ka Nuamboonlue
 

En vedette (20)

Maialen
MaialenMaialen
Maialen
 
Angel Meetup 2012
Angel Meetup 2012Angel Meetup 2012
Angel Meetup 2012
 
Amaia lopez escolar activity 1
Amaia lopez escolar activity 1Amaia lopez escolar activity 1
Amaia lopez escolar activity 1
 
71071733[1]
71071733[1]71071733[1]
71071733[1]
 
Overview of haggai zechariah and malachi
Overview of haggai zechariah and malachiOverview of haggai zechariah and malachi
Overview of haggai zechariah and malachi
 
Buddhist wisdom way
Buddhist wisdom wayBuddhist wisdom way
Buddhist wisdom way
 
Daftarhadir&nilai statistik 1415
Daftarhadir&nilai statistik 1415Daftarhadir&nilai statistik 1415
Daftarhadir&nilai statistik 1415
 
Changing the world
Changing the worldChanging the world
Changing the world
 
JH G321 Draft and layout for all construction parts
JH G321 Draft and layout for all construction partsJH G321 Draft and layout for all construction parts
JH G321 Draft and layout for all construction parts
 
Evaluation Question 2
Evaluation Question 2Evaluation Question 2
Evaluation Question 2
 
Informe general
Informe generalInforme general
Informe general
 
Case study task
Case study taskCase study task
Case study task
 
ツイートするだけクライアント
ツイートするだけクライアントツイートするだけクライアント
ツイートするだけクライアント
 
God's generous grace and our vocations
God's generous grace and our vocationsGod's generous grace and our vocations
God's generous grace and our vocations
 
Qc runtime parameters_for_qtp_tests
Qc runtime parameters_for_qtp_testsQc runtime parameters_for_qtp_tests
Qc runtime parameters_for_qtp_tests
 
Security in Cloud-based Cyber-physical Systems
Security in Cloud-based Cyber-physical SystemsSecurity in Cloud-based Cyber-physical Systems
Security in Cloud-based Cyber-physical Systems
 
การพัฒนามนุษย์และสังคมเพื่อความเป็นไท ความหมาย
การพัฒนามนุษย์และสังคมเพื่อความเป็นไท ความหมายการพัฒนามนุษย์และสังคมเพื่อความเป็นไท ความหมาย
การพัฒนามนุษย์และสังคมเพื่อความเป็นไท ความหมาย
 
Daftarhadir&nilai statistik
Daftarhadir&nilai statistikDaftarhadir&nilai statistik
Daftarhadir&nilai statistik
 
Pengembangan kurikulum
Pengembangan kurikulumPengembangan kurikulum
Pengembangan kurikulum
 
алькеева аида
алькеева аидаалькеева аида
алькеева аида
 

Similaire à Science

Robust and sensitive method of
Robust and sensitive method ofRobust and sensitive method of
Robust and sensitive method ofijbesjournal
 
Review: Nonlinear Techniques for Analysis of Heart Rate Variability
Review: Nonlinear Techniques for Analysis of Heart Rate VariabilityReview: Nonlinear Techniques for Analysis of Heart Rate Variability
Review: Nonlinear Techniques for Analysis of Heart Rate VariabilityIJRES Journal
 
Beer_Leurer_association_ANS_control_CI_post_stroke_vs_age-matched_heatlhy_con...
Beer_Leurer_association_ANS_control_CI_post_stroke_vs_age-matched_heatlhy_con...Beer_Leurer_association_ANS_control_CI_post_stroke_vs_age-matched_heatlhy_con...
Beer_Leurer_association_ANS_control_CI_post_stroke_vs_age-matched_heatlhy_con...mariapzabalza
 
Data-driven search for causal paths 
in cardiorespiratory parameters
Data-driven search for causal paths 
in cardiorespiratory parametersData-driven search for causal paths 
in cardiorespiratory parameters
Data-driven search for causal paths 
in cardiorespiratory parametersMarcel Młyńczak
 
Study of Dynamics of Some Human Diseases on the Base of Fractal Approach (“Ra...
Study of Dynamics of Some Human Diseases on the Base of Fractal Approach (“Ra...Study of Dynamics of Some Human Diseases on the Base of Fractal Approach (“Ra...
Study of Dynamics of Some Human Diseases on the Base of Fractal Approach (“Ra...crimsonpublishersOJCHD
 
Hypoxia acute mountain sickness and cerebral edema
Hypoxia acute mountain sickness and cerebral edemaHypoxia acute mountain sickness and cerebral edema
Hypoxia acute mountain sickness and cerebral edemaGuus Schoonman
 
Control of Nonlinear Heartbeat Models under Time- Delay-Switched Feedback Usi...
Control of Nonlinear Heartbeat Models under Time- Delay-Switched Feedback Usi...Control of Nonlinear Heartbeat Models under Time- Delay-Switched Feedback Usi...
Control of Nonlinear Heartbeat Models under Time- Delay-Switched Feedback Usi...idescitation
 
MEDITATION: ITS TREMENDOUS IMPACT ON HEART RATE VARIABILITY
MEDITATION: ITS TREMENDOUS IMPACT ON HEART RATE VARIABILITYMEDITATION: ITS TREMENDOUS IMPACT ON HEART RATE VARIABILITY
MEDITATION: ITS TREMENDOUS IMPACT ON HEART RATE VARIABILITYcscpconf
 
A M ODIFIED M ETHOD F OR P REDICTIVITY OF H EART R ATE V ARIABILITY
A M ODIFIED  M ETHOD  F OR P REDICTIVITY OF  H EART  R ATE V ARIABILITYA M ODIFIED  M ETHOD  F OR P REDICTIVITY OF  H EART  R ATE V ARIABILITY
A M ODIFIED M ETHOD F OR P REDICTIVITY OF H EART R ATE V ARIABILITYcsandit
 
Hemodynamic response function at rest and effects of autonomic nervous system...
Hemodynamic response function at rest and effects of autonomic nervous system...Hemodynamic response function at rest and effects of autonomic nervous system...
Hemodynamic response function at rest and effects of autonomic nervous system...danielemarinazzo
 
Heart rate variability task force
Heart rate variability   task forceHeart rate variability   task force
Heart rate variability task forceCecilia Nunez
 
A STUDY ON IMPACT OF ALCOHOL AMONG YOUNG INDIAN POPULATION USING HRV ANALYSIS
A STUDY ON IMPACT OF ALCOHOL AMONG YOUNG INDIAN POPULATION USING HRV ANALYSISA STUDY ON IMPACT OF ALCOHOL AMONG YOUNG INDIAN POPULATION USING HRV ANALYSIS
A STUDY ON IMPACT OF ALCOHOL AMONG YOUNG INDIAN POPULATION USING HRV ANALYSISijcseit
 
A study on impact of alcohol among young
A study on impact of alcohol among youngA study on impact of alcohol among young
A study on impact of alcohol among youngijcseit
 
Assessment of Cardiac Autonomic Nerve Function Status by Heart Rate Variabili...
Assessment of Cardiac Autonomic Nerve Function Status by Heart Rate Variabili...Assessment of Cardiac Autonomic Nerve Function Status by Heart Rate Variabili...
Assessment of Cardiac Autonomic Nerve Function Status by Heart Rate Variabili...MatiaAhmed
 

Similaire à Science (20)

Robust and sensitive method of
Robust and sensitive method ofRobust and sensitive method of
Robust and sensitive method of
 
Review: Nonlinear Techniques for Analysis of Heart Rate Variability
Review: Nonlinear Techniques for Analysis of Heart Rate VariabilityReview: Nonlinear Techniques for Analysis of Heart Rate Variability
Review: Nonlinear Techniques for Analysis of Heart Rate Variability
 
Beer_Leurer_association_ANS_control_CI_post_stroke_vs_age-matched_heatlhy_con...
Beer_Leurer_association_ANS_control_CI_post_stroke_vs_age-matched_heatlhy_con...Beer_Leurer_association_ANS_control_CI_post_stroke_vs_age-matched_heatlhy_con...
Beer_Leurer_association_ANS_control_CI_post_stroke_vs_age-matched_heatlhy_con...
 
Data-driven search for causal paths 
in cardiorespiratory parameters
Data-driven search for causal paths 
in cardiorespiratory parametersData-driven search for causal paths 
in cardiorespiratory parameters
Data-driven search for causal paths 
in cardiorespiratory parameters
 
Study of Dynamics of Some Human Diseases on the Base of Fractal Approach (“Ra...
Study of Dynamics of Some Human Diseases on the Base of Fractal Approach (“Ra...Study of Dynamics of Some Human Diseases on the Base of Fractal Approach (“Ra...
Study of Dynamics of Some Human Diseases on the Base of Fractal Approach (“Ra...
 
e12705.full
e12705.fulle12705.full
e12705.full
 
Hypoxia acute mountain sickness and cerebral edema
Hypoxia acute mountain sickness and cerebral edemaHypoxia acute mountain sickness and cerebral edema
Hypoxia acute mountain sickness and cerebral edema
 
Control of Nonlinear Heartbeat Models under Time- Delay-Switched Feedback Usi...
Control of Nonlinear Heartbeat Models under Time- Delay-Switched Feedback Usi...Control of Nonlinear Heartbeat Models under Time- Delay-Switched Feedback Usi...
Control of Nonlinear Heartbeat Models under Time- Delay-Switched Feedback Usi...
 
MEDITATION: ITS TREMENDOUS IMPACT ON HEART RATE VARIABILITY
MEDITATION: ITS TREMENDOUS IMPACT ON HEART RATE VARIABILITYMEDITATION: ITS TREMENDOUS IMPACT ON HEART RATE VARIABILITY
MEDITATION: ITS TREMENDOUS IMPACT ON HEART RATE VARIABILITY
 
A M ODIFIED M ETHOD F OR P REDICTIVITY OF H EART R ATE V ARIABILITY
A M ODIFIED  M ETHOD  F OR P REDICTIVITY OF  H EART  R ATE V ARIABILITYA M ODIFIED  M ETHOD  F OR P REDICTIVITY OF  H EART  R ATE V ARIABILITY
A M ODIFIED M ETHOD F OR P REDICTIVITY OF H EART R ATE V ARIABILITY
 
Wet cupping therapy restores sympathovagal
Wet cupping therapy restores sympathovagalWet cupping therapy restores sympathovagal
Wet cupping therapy restores sympathovagal
 
International Journal of Cardiovascular Diseases & Diagnosis
International Journal of Cardiovascular Diseases & DiagnosisInternational Journal of Cardiovascular Diseases & Diagnosis
International Journal of Cardiovascular Diseases & Diagnosis
 
CHAOS ANALYSIS OF HRV
CHAOS ANALYSIS OF HRVCHAOS ANALYSIS OF HRV
CHAOS ANALYSIS OF HRV
 
Hemodynamic response function at rest and effects of autonomic nervous system...
Hemodynamic response function at rest and effects of autonomic nervous system...Hemodynamic response function at rest and effects of autonomic nervous system...
Hemodynamic response function at rest and effects of autonomic nervous system...
 
X35129134
X35129134X35129134
X35129134
 
paper_ANEC_2010
paper_ANEC_2010paper_ANEC_2010
paper_ANEC_2010
 
Heart rate variability task force
Heart rate variability   task forceHeart rate variability   task force
Heart rate variability task force
 
A STUDY ON IMPACT OF ALCOHOL AMONG YOUNG INDIAN POPULATION USING HRV ANALYSIS
A STUDY ON IMPACT OF ALCOHOL AMONG YOUNG INDIAN POPULATION USING HRV ANALYSISA STUDY ON IMPACT OF ALCOHOL AMONG YOUNG INDIAN POPULATION USING HRV ANALYSIS
A STUDY ON IMPACT OF ALCOHOL AMONG YOUNG INDIAN POPULATION USING HRV ANALYSIS
 
A study on impact of alcohol among young
A study on impact of alcohol among youngA study on impact of alcohol among young
A study on impact of alcohol among young
 
Assessment of Cardiac Autonomic Nerve Function Status by Heart Rate Variabili...
Assessment of Cardiac Autonomic Nerve Function Status by Heart Rate Variabili...Assessment of Cardiac Autonomic Nerve Function Status by Heart Rate Variabili...
Assessment of Cardiac Autonomic Nerve Function Status by Heart Rate Variabili...
 

Dernier

Introduction to Sports Injuries by- Dr. Anjali Rai
Introduction to Sports Injuries by- Dr. Anjali RaiIntroduction to Sports Injuries by- Dr. Anjali Rai
Introduction to Sports Injuries by- Dr. Anjali RaiGoogle
 
SWD (Short wave diathermy)- Physiotherapy.ppt
SWD (Short wave diathermy)- Physiotherapy.pptSWD (Short wave diathermy)- Physiotherapy.ppt
SWD (Short wave diathermy)- Physiotherapy.pptMumux Mirani
 
Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)Mohamed Rizk Khodair
 
Presentació "Real-Life VR Integration for Mild Cognitive Impairment Rehabilit...
Presentació "Real-Life VR Integration for Mild Cognitive Impairment Rehabilit...Presentació "Real-Life VR Integration for Mild Cognitive Impairment Rehabilit...
Presentació "Real-Life VR Integration for Mild Cognitive Impairment Rehabilit...Badalona Serveis Assistencials
 
PERFECT BUT PAINFUL TKR -ROLE OF SYNOVECTOMY.pptx
PERFECT BUT PAINFUL TKR -ROLE OF SYNOVECTOMY.pptxPERFECT BUT PAINFUL TKR -ROLE OF SYNOVECTOMY.pptx
PERFECT BUT PAINFUL TKR -ROLE OF SYNOVECTOMY.pptxdrashraf369
 
epilepsy and status epilepticus for undergraduate.pptx
epilepsy and status epilepticus  for undergraduate.pptxepilepsy and status epilepticus  for undergraduate.pptx
epilepsy and status epilepticus for undergraduate.pptxMohamed Rizk Khodair
 
Informed Consent Empowering Healthcare Decision-Making.pptx
Informed Consent Empowering Healthcare Decision-Making.pptxInformed Consent Empowering Healthcare Decision-Making.pptx
Informed Consent Empowering Healthcare Decision-Making.pptxSasikiranMarri
 
Glomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and  determinants of glomerular filtration .pptxGlomerular Filtration and  determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptxDr.Nusrat Tariq
 
Study on the Impact of FOCUS-PDCA Management Model on the Disinfection Qualit...
Study on the Impact of FOCUS-PDCA Management Model on the Disinfection Qualit...Study on the Impact of FOCUS-PDCA Management Model on the Disinfection Qualit...
Study on the Impact of FOCUS-PDCA Management Model on the Disinfection Qualit...MehranMouzam
 
Presentation on Parasympathetic Nervous System
Presentation on Parasympathetic Nervous SystemPresentation on Parasympathetic Nervous System
Presentation on Parasympathetic Nervous SystemPrerana Jadhav
 
low cost antibiotic cement nail for infected non union.pptx
low cost antibiotic cement nail for infected non union.pptxlow cost antibiotic cement nail for infected non union.pptx
low cost antibiotic cement nail for infected non union.pptxdrashraf369
 
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisVarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisGolden Helix
 
Basic principles involved in the traditional systems of medicine PDF.pdf
Basic principles involved in the traditional systems of medicine PDF.pdfBasic principles involved in the traditional systems of medicine PDF.pdf
Basic principles involved in the traditional systems of medicine PDF.pdfDivya Kanojiya
 
Statistical modeling in pharmaceutical research and development.
Statistical modeling in pharmaceutical research and development.Statistical modeling in pharmaceutical research and development.
Statistical modeling in pharmaceutical research and development.ANJALI
 
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdfLippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdfSreeja Cherukuru
 
Apiculture Chapter 1. Introduction 2.ppt
Apiculture Chapter 1. Introduction 2.pptApiculture Chapter 1. Introduction 2.ppt
Apiculture Chapter 1. Introduction 2.pptkedirjemalharun
 
Presentation for Bella Mahl 2024-03-28-24-MW-Overview-Bella.pptx
Presentation for Bella Mahl 2024-03-28-24-MW-Overview-Bella.pptxPresentation for Bella Mahl 2024-03-28-24-MW-Overview-Bella.pptx
Presentation for Bella Mahl 2024-03-28-24-MW-Overview-Bella.pptxpdamico1
 
Radiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptxRadiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptxDr. Dheeraj Kumar
 
SGK HÓA SINH NĂNG LƯỢNG SINH HỌC 2006.pdf
SGK HÓA SINH NĂNG LƯỢNG SINH HỌC 2006.pdfSGK HÓA SINH NĂNG LƯỢNG SINH HỌC 2006.pdf
SGK HÓA SINH NĂNG LƯỢNG SINH HỌC 2006.pdfHongBiThi1
 

Dernier (20)

Introduction to Sports Injuries by- Dr. Anjali Rai
Introduction to Sports Injuries by- Dr. Anjali RaiIntroduction to Sports Injuries by- Dr. Anjali Rai
Introduction to Sports Injuries by- Dr. Anjali Rai
 
SWD (Short wave diathermy)- Physiotherapy.ppt
SWD (Short wave diathermy)- Physiotherapy.pptSWD (Short wave diathermy)- Physiotherapy.ppt
SWD (Short wave diathermy)- Physiotherapy.ppt
 
Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)
 
Presentació "Real-Life VR Integration for Mild Cognitive Impairment Rehabilit...
Presentació "Real-Life VR Integration for Mild Cognitive Impairment Rehabilit...Presentació "Real-Life VR Integration for Mild Cognitive Impairment Rehabilit...
Presentació "Real-Life VR Integration for Mild Cognitive Impairment Rehabilit...
 
PERFECT BUT PAINFUL TKR -ROLE OF SYNOVECTOMY.pptx
PERFECT BUT PAINFUL TKR -ROLE OF SYNOVECTOMY.pptxPERFECT BUT PAINFUL TKR -ROLE OF SYNOVECTOMY.pptx
PERFECT BUT PAINFUL TKR -ROLE OF SYNOVECTOMY.pptx
 
epilepsy and status epilepticus for undergraduate.pptx
epilepsy and status epilepticus  for undergraduate.pptxepilepsy and status epilepticus  for undergraduate.pptx
epilepsy and status epilepticus for undergraduate.pptx
 
Informed Consent Empowering Healthcare Decision-Making.pptx
Informed Consent Empowering Healthcare Decision-Making.pptxInformed Consent Empowering Healthcare Decision-Making.pptx
Informed Consent Empowering Healthcare Decision-Making.pptx
 
Glomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and  determinants of glomerular filtration .pptxGlomerular Filtration and  determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptx
 
Study on the Impact of FOCUS-PDCA Management Model on the Disinfection Qualit...
Study on the Impact of FOCUS-PDCA Management Model on the Disinfection Qualit...Study on the Impact of FOCUS-PDCA Management Model on the Disinfection Qualit...
Study on the Impact of FOCUS-PDCA Management Model on the Disinfection Qualit...
 
Presentation on Parasympathetic Nervous System
Presentation on Parasympathetic Nervous SystemPresentation on Parasympathetic Nervous System
Presentation on Parasympathetic Nervous System
 
low cost antibiotic cement nail for infected non union.pptx
low cost antibiotic cement nail for infected non union.pptxlow cost antibiotic cement nail for infected non union.pptx
low cost antibiotic cement nail for infected non union.pptx
 
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic AnalysisVarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
VarSeq 2.6.0: Advancing Pharmacogenomics and Genomic Analysis
 
Epilepsy
EpilepsyEpilepsy
Epilepsy
 
Basic principles involved in the traditional systems of medicine PDF.pdf
Basic principles involved in the traditional systems of medicine PDF.pdfBasic principles involved in the traditional systems of medicine PDF.pdf
Basic principles involved in the traditional systems of medicine PDF.pdf
 
Statistical modeling in pharmaceutical research and development.
Statistical modeling in pharmaceutical research and development.Statistical modeling in pharmaceutical research and development.
Statistical modeling in pharmaceutical research and development.
 
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdfLippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
Lippincott Microcards_ Microbiology Flash Cards-LWW (2015).pdf
 
Apiculture Chapter 1. Introduction 2.ppt
Apiculture Chapter 1. Introduction 2.pptApiculture Chapter 1. Introduction 2.ppt
Apiculture Chapter 1. Introduction 2.ppt
 
Presentation for Bella Mahl 2024-03-28-24-MW-Overview-Bella.pptx
Presentation for Bella Mahl 2024-03-28-24-MW-Overview-Bella.pptxPresentation for Bella Mahl 2024-03-28-24-MW-Overview-Bella.pptx
Presentation for Bella Mahl 2024-03-28-24-MW-Overview-Bella.pptx
 
Radiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptxRadiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptx
 
SGK HÓA SINH NĂNG LƯỢNG SINH HỌC 2006.pdf
SGK HÓA SINH NĂNG LƯỢNG SINH HỌC 2006.pdfSGK HÓA SINH NĂNG LƯỢNG SINH HỌC 2006.pdf
SGK HÓA SINH NĂNG LƯỢNG SINH HỌC 2006.pdf
 

Science

  • 1. Medical Hypotheses (1998) 51, 367-376 © Harcourt Brace & Co. Ltd 1998 Fractal organization of the pointwise correlation dimension of the heart rate E. NAHSHONI, E. ADLER*, S. LANIADO*, G. KEREN* Department E, The Gehah Psychiatric Hospital, Petah-Tiqva, and Sackler School of Medicine, Tel Aviv, Israeb *Department of Cardiology, Tel Aviv Medical Center, Tel Aviv, and Sackler School of Medicine, Tel Aviv, Israel. Correspondence to: E. Nahshoni, POB 102, 49100 Petah-Tiqva, Israel (Phone: +972 3 9258258; Fax: + 972 3 9241041) Abstract - - Objective: To depict and quantify the degree of organization of the heart rate variability (HRV) in normal subjects. Methods: A modified algorithm was created to estimate series of "point-dimensions" (PD2) from interbeat (R-R) interval series of 10 healthy subjects (21-56 years). Our innovation is twofold: (i) we quantified instances of low-dimensional chaos, random fluctuations, and those for which our method failed to provide either (due to poor statistics); (ii) consecutive subepochs of PD2s underwent a relative dispersion (RD) analysis, yielding an index (D) which quantifies the dynamical organization of the heart rate generator. Results: The mean values of PD2 series varied between 4.58 and 5.88 (mean +_SD= 5.21 +_0.41, n = 10). For group 1 (21-30 years, n = 6) we found an averaged PD2 of 5.49 _+0.27, while for group 2 (47-56 years, n = 4) PD2 averaged 4.79 +_.0.17. The RD analysis performed for subepochs of PD2s yielded both instances obeying fractal scaling (D < 1.5) and stochasticity (D > 1.5). The average D for group 1 was 1.39 + 0.04 (14 subepochs) and for group 2, 1.20 _+0.008 (8 subepochs). Paired t-test and Hartley F-max test for comparison between D values and homogeneity of variance between the two groups were performed, yielding P-values 0.004 and 0.02, respectively. Conclusions: The complexity of the HRV seems to be modulated by a non-random fractal mechanism of a 'hyperchaotic' system, i.e. it can be hypothesized to contain more than one attractor. Also, our results support the 'chaos hypothesis' put forth recently, namely, the complexity of the cardiovascular dynamics is reduced with aging. The index of relative dispersion of the dimensional complexity has to be tested in various clinico-pathological settings, in order to corroborate its value as a potential new physiological measure. Introduction frequency and phases of biological oscillators, or to the coupling of various regulatory feedback loops, Physiological systems have long been recognized to thus engaging nonlinear mechanisms for elucidation display complex temporal fluctuations, even during of the dynamics. Although, as in the physical sciences, 'steady state' conditions. Attempts were made to attri- solutions have resulted in 'linearizations', only during bute them to random influences, which perturb the the last decade has a natural link been drawn between Received 28 April 1997 Accepted 12 June 1997 367
  • 2. 368 MEDICAL HYPOTHESES' the mathematico-physical field of nonlinear dynamics theses, which motivated ongoing research efforts and physiology. This has triggered an ongoing trend meant to quantify the dynamical characteristics of of 'paradigm shift' in the medical sciences and in the heart rate dynamics under the assumption that biological thinking in general. it evolves on a low-dimensional 'strange attractor'. Since the advent of digital processing, the heart rate These attempts were based mainly on dimensional became the most accessible and reliable signal for analysis, which resulted in correlation dimensions analysis among cardiovascular variables. The heart (interpreted as a static measure of the number of rate variability (HRV) is traditionally assessed using independent variables necessary to specify the state of frequency (spectral analysis) and time (standard de- the system under study), ranging between 3.6 and 5.2 viations, interval occurrence histograms, etc.) domain in normal subjects (17). This was supported later, by techniques. Using such techniques a complex coupling introducing another measure of deterministic chaos, with respiration, baroreceptors, the nervous system, i.e. the largest Lyapunov exponent which yielded a body temperature, metabolic rate, hormones, sleep finite positive value, thus demonstrating the property cycles, etc. was revealed. For example, spectral analysis, of sensitivity to initial conditions, which is the hall- which exposed activity bands in the frequency mark of chaotic behavior (18). But later estimates domain comprising thermoregulation (~0.05Hz), of the correlation dimension were found to be much baroreflex control of peripheral resistance (~ 0.1 Hz) higher (-8.5) than previously reported, thus pre- and respiratory control (~ 0.2 Hz), was combined cluding firm conclusions as to the true nature of the with pharmacological blockade to attribute the lower- heart rate generator (19). band fluctuations (0.04--0.15 Hz) to the joint influence Recently, other modified measures of dynamical of the sympathetic and parasympathetic arms of the complexity, mostly suited for nonstationary, noisy, autonomic nervous system, while the higher fre- and limited record length signals, have been intro- quency band (0.15-0.4 Hz) was shown to be purely duced. Among them is the estimation of the pointwise parasympathetically mediated. The spectral signature correlation dimension (PD2), which provides more of HRV was also related to various physiological information about the temporo-spatial evolution of and pathophysiological settings, such as standing, the dominant complexity of the heartbeat (20,21). hemorrhage and hypotension, which enhance the low This technique was applied to a very limited number frequency fluctuations, while exercise and standing of subjects, from which no firm conclusions could decrease the respiratory fluctuations. From the clinico- be drawn, except for one clinical study which corre- pathological viewpoint, patients with heart failure lated a reduced dynamical complexity hours before have diminished power spectrum at frequencies above the occurrence of lethal arrhythmias in high-risk ~ 0.02 Hz (1-7). The other arm of traditional analysis, patients (22). the time domain analysis, has related decreased HRV In the light of the open questions and computa- in diabetes mellitus, ischemic heart disease, conges- tional restrictions in this growing field of research, tive heart failure (8), and also associated an increased we addressed the issue of the irregular nature of the mortality in patients after acute myocardial infarction HRV in 10 healthy subjects. We computed correlation (9). dimensions and the series of pointwise dimensions. Taken together, these techniques have several short- We also introduced a modified version of the point- comings. For example, spectral analysis is a method wise dimension algorithm, which, we believe, can mostly suited for linear systems, while physiological depict both instances of low-dimensional chaos and systems are inherently nonlinear. Also, time domain stochasticity. The complex relation between them analysis, which is basically an averaging technique, was investigated using fractal techniques. The physio- overlooks the dynamical nature. Thus, it appears that logical and clinical importance of the measure we these techniques are often insufficient to characterize introduced is still unknown. the complex behavior of the heart rate generator. Since the last decade, nonlinear methods of analysis, based on the paradigm of deterministic chaos (10), Methods have permeated the realm of biomedical signal analysis (11). This was motivated by the observation Subjects of an inverse power-law scaling (also called 1/f Ten volunteers, aged 21-56 (6 males, 4 females) spectrum), which some chaotic systems may display, without symptoms or history of heart disease and and by its association to the fractal concept (mani- under no medication, were recruited for the study. fested by self-similarity over multiple orders of Their surface ECG, which showed no signs of patho- temporal magnitude) (12-16). In the case of heart rate logy, was recorded at rest in a supine position, during dynamics, these observations heralded new hypo- quite spontaneous breathing (~ 15 breaths/min) for
  • 3. FRACTAL ORGANIZATION IN HEART RATE 369 20 rain. All recordings were done between 10 and series were time-delayed for successive embedding 12 a.m., and each subject was allowed to adjust dimensions (from m = 1 to m = 16). Within a given comfortably for 10 min in a supine position before the embedding dimension, the distance (r) of each point data were collected. They all gave informed consent to every other point was calculated. Their absolute to the protocol. values were rank-ordered from the smallest to the largest, and the range from the smallest to the largest Data aquisition value was broken up into discrete intervals. Then, the number of times a distance fell within an interval was The ECG signals were continuously recorded using a counted. A cumulative histogram was then formed laptop-based HIPEC ANALIZER HA-200/AH system by summing the number of instances for which a (Aerotel - - computerized systems, Israel) with a distance was less than or equal to the upper boundary sampling rate of 1000 Hz, and 16 bit signal resolu- of the interval. This is the correlation integral C(r). tion. The ECG records were transferred to a personal C(r) was then plotted as a function of r on a log-log computer for off-line analysis which started with a representation, resulting in a sigmoid-shaped curve quality control procedure: visual inspection, baseline (in this case implying chaotic dynamics). The slope shift evaluation and a 'moving average' (four points over the largest linear range (if there is one) was averaging in succession along the record) for signal to measured, using linear regression (with a regression noise ratio improvement. Then the interbeat intervals coefficient R 2 > 0.98). In this scaling range the local (R-R) were computed using an algorithm developed exponent is constant and ~ d InC(r)/d In(r). Then, the in our laboratory, with which an R wave threshold embedding dimension was advanced and its corre- detection was combined with first derivative and QRS sponding slope was calculated. These slopes were width considerations, for an accurate R wave detection. then plotted versus the embedding dimension, looking for a saturation region, i.e. a region in which the Attractor reconstruction slopes no longer grow. This plateau region was then Usually the experimentalist is confronted with in- considered as the correlation dimension (D2), and its ability to gain access to m simultaneous recordings value was calculated with a weighted average tech- necessary to describe the system's trajectory in nique (each value in the plateau region was weighted m-dimensional phase space. Thus, only one scalar by the variance of its underlying slope calculation). observable can be monitored as a function of time. This process was also performed for randomized Fortunately, it has been shown that certain properties versions of the R - R series (with similar mean and of the dynamics are feasible through the method of variance) in order to provide confidence limits for our time delays using Taken's theorem, as follows (23). calculations. Consider a single time series regularly spaced in time: xi = x%), i = 1..... N. Then a time lag "~is intro- Pointwise dimension of R-R intervals duced, such that m-dimensional vectors are created: xi= [x(ti), x(ti + "c)..... x(ti+ (m-1)x)]. This process is The 'point' estimate of the correlation dimension termed embedding, and m is called the embedding (PD2) begins with the time lag calculation, followed dimension. Through this reconstruction a phase by the embedding procedure, as described before. space is spanned and dynamical and metric measures Then, starting with the initial point in the series, its (Lyapunov exponents, dimensions) may be accessible. local correlation integral is calculated, i.e. the dis- tances are taken with respect to this point and ranked- ordered as usual, for each embedding dimension Correlation dimension of R-R intervals (m = 1..... 16). The slopes for each m were evaluated The correlation dimension was calculated using the using a linear regression (R2> 0.98), and a slope method of Grassberger and Procaccia (G-P) as follows values, corresponding to m = 8 ..... 16 were stored in (24). First, for each R - R interval series, the normal- a file. The algorithm steps to the next point in the ized autocorrelation function given by: series, and the whole procedure is repeated until the whole file is exhausted. Then comes the procedure ~g('~) = {(I/N) £[R-R)i - < (R-R) >][(R-R)i+x - that we call slope convergence, which calculates the < (R-R) >] }/{(I/N) Z[R-R)i - < (R-R) >]2} slope of the 9 slopes versus the embedding dimensions where (m = 8 ..... 16) using linear regression. Our innova- tion was to subject this to the imposition of three < (R-R) > = (l/N) Z (R-R)/ conditions as follows: Ill if the slope was less than was constructed, and its first zero crossing was calcu- 0.5 and larger than -0.23, we considered this as good lated to provide the time lag (x) in beats. Then, the convergence and the PD2 could be estimated using
  • 4. 370 MEDICAL HYPOTHESES the weighted average technique as described before; dimensions was needed. Homogeneity of variance (ii) if the slope was equal or larger than 0.5, we was tested by the Hartley F-max test. Statistical considered it as if no saturation existed, and at significance was assumed if the null hypothesis could this point (or time), the system probably manifested be rejected at the 0.05 probability level. a random fluctuation. In order to incorporate such a behavior into the sequence of PD2s, we decided, quite arbitrarily, to take the average of the two highest Results slope estimates, as the point-dimension, when such a condition appears; (iii) if the slope was equal to Thc correlation dimension (D2) of R-R intervals or less than --0.23, we considered it as if no slope varied from 3.29 to 5.16, with an overall mean of convergence existed, and the dimensional estimate 4.01 ± 0.54 (Table 1). Fig. la illustrates one of the at this point was excluded, possibly because of poor series of R-R intervals. This corresponding normal- statistics. ized autocorrelation function is shown in Fig. lb. The The results of the PD2 series were 'assigned' first zero crossing (x), in this case was equal to 6 according to the three conditions mentioned above. beats. The correlation integral (C(r)) for embedding This provided us with the ability to discriminate the dimensions (m = 2,4,6,9,12,16) is shown in Fig. 2a, points which manifested low-dimensional chaos and while the calculated slopes in the linear regions of random behavior, from those for which a dimensional the log-C(r) representation, versus the embedding estimate could not be achieved. From the above dimension, is shown in Fig. 2b. Note the convergence output files we extracted sequences of dimensional towards a dimensional value of 4. Randomized ver- subepochs, which were then suited for the relative sions of the R-R intervals have demonstrated, as dispersion analysis. expected, non-convergence (Fig. 2c). A sequence of pointwise dimensions (PD2s) versus the reference point is shown in Fig. 3a. Note three Dispersion analysis regions in the dimensional complexity plot, i.e. high values (PD2 > 6), low-dimensional region (3 > PD2 < 6) There are three basic methods of dispersion analysis and zero-valued reference points, corresponding to that can be applied to temporal observations (25). One non-convergence due to poor statistics. This can be of them, adopted in our study for each sequence of seen from the histogram (Fig. 3b) showing the distrib- calculated pointwise dimensions, is called relative ution of the rounded dimensional values, including dispersion (RD) analysis. Our intention was to try and the points corresponding to stochasticity and to non- see if the temporal evolution of PD2 series obeys any calculability at both ends of the figure. For the subject scaling properties. Thus for each subject, this simple shown in the figure the average PD2 was 5.37 ± 0.93. algorithm goes as follows: first, the mean, standard In Fig. 4, four subepochs, each comprising ~150 PD2 deviation (SD), and RD% (= 100 x SD/mean) of the values (corresponding to an average of about 2.5 original PD2 series were calculated. Then, pairs of minutes'-record-length each) are shown. In Fig. 5 the adjacent PD2s were averaged and their RD% values logarithmic plot of the RD(%) versus the interval were calculated, thus doubling the interval length. Recursive pairing with doubling of each previous interval length was carried out while its correspond- Table 1 Correlation dimension (D2) of 10 healthy ing RD% was calculated. This was done until the subjects at rest whole record was exhausted. By plotting the RD% against the interval length on a logarithmic scale, the Gender Age (years) HR ± SD Correlation dimension slope was estimated using a least-squares linear fit. (beat/rain) (D2 ± ZkD2) The fractal dimension (D) could thus be extracted from the slope (slope --- l-D). In order to confirm the M 21 69.1 ± 5.6 4.51 ± 0.13 temporal organization of the PD2 series, randomized F 25 65.5 ± 3.0 3.58± 0.07 versions based on similar statistical characteristics M 26 65.2 ± 2.5 3.93 ± 0.09 F 28 67.6± 3.5 5.16 ± 0.02 (number of points, mean and standard deviation) were M 30 57.6 ± 4.6 3.99 ± 0.16 generated, and their RD analysis was also performed. M 30 54.2±2.3 4.50±0.19 M 47 71.4± 3.9 3.87 ± 0.21 M 56 60.9 ± 3.0 3.29 ± 0.19 F 56 64.7 ± 2.3 3.48 ± 0.21 Statistical analysis F 56 66.8 ± 2.6 3.77 ± 0.03 All data are expressed as mean ± SD. A paired t-test mean ± SD 37.5 ± 13.7 64.3 ± 5.0 4.01 ± 0.54 was performed when comparison between fractal
  • 5. FRACTALORGANIZA~ONINHEARTRATE 371 1.25 0.75 e- •- 0.5- I e¢- 0.25 0 1 500 1000 Beat number 0.7 0.6 0.5 0.4-- 0.3-- 0.2 0.1- 0 -0.1 .'v , , .... 'IW ,v,' ' V V_ -0.2 m 100 200 300 b T Fig. 1 (a) R - R intervals for one of the subjects (1296 intervals, 20 min). (b) The normalized autocorrelation function of R - R intervals shown in (a). The first zero crossing was found to be 6 beats. length (measured in beat number) for one of the 850. The overall mean values of the PD2 series varied subepochs is shown. Its slope provides the fractal between 4.5 and 5.88 (mean = 5.21 ± 0.41, n = 10), dimension of the dimensional complexity at a parti- but the mean PD2s of the various subepochs were cular subepoch. smaller than the overall average, at least during one Table 2 summarizes the results of the fractal subepoch for each subject. We divided the subjects dimensions (D) of the subepochs of series of PD2s. into two groups according to their age. For group 1 The shortest subepoch consisted of 80 consecutive (21-30 years) the average PD2 varied between 5.19 dimensional values, while the longest consisted of and 5.88 (mean = 5.49 ± 0.27, n = 6), while the
  • 6. 372 MEDICAL HYPOTHESES 0 -1, -2. -3 to t- -4 -5 -6 -7 1'5 ' ' 2~0 . . . . 2~5 . . . . Inr Emb 9 --K--- Emb 12 ~ Emb 16 5 8 C C 0 O r r 4 r ? ?6 i 3 . i 0 O n n 4 d i 2 ? m m e e 2 n 1 [I 0 O n 0 n . . . . . . . . . . . . . . 0 . . . . . . . . 110 111 I i I4 I 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 2 3 4 5 6 7 8 9 1 13 1 1 16 b Embedding dimension c Embedding dimension Fig. 2 The correlation integral C(r) versus r on a logarithmicplot. Seen are embeddingdimensions m = 2, 4, 6, 9, 12, 16. (b) The slope of the scaling region as a function of the embeddingdimension (m), for a healthy subject (26 years). Note the saturation towards a correlation dimension (D2) estimate of ~4. (c) For a randomlygenerated version of R-R intervals, the slope estimates of In C(r) versus lnr, as a functionof the embeddingdimension, do not saturate. relative dispersion analysis of their consecutive PD2 Discussion series yielded both instances of fractal scaling (D < 1.5) and stochasticity (D > 1.5). The averaged The concept of fractals, first coined by B. Mandelbrot fractal dimension for this group was 1.39 4-0.04 (26), and its association with chaos theory, heralded (14 subepochs). In group 2 (47-56 years), the PD2 novel insights into the realm of structural and mean values ranged between 4.58 and 5.03 (mean = dynamical variability in the medical sciences (27) 4.79 ± 0.17, n = 4). Note that in group 2 the fractal and biology in general (11). During the last decade, estimates ranged between 1.09 and 1.33 (mean = the intimate connection between deterministic chaos 1.20 ± 0.008, 8 subepochs), i.e. never exceeded 1.5. and fractal geometry has stimulated ongoing research The t-test and the F-test showed statistical signi- efforts to quantify the dynamical aspects of the heart ficance when the means and variances of the fractal rate generator. Babloyantz and Destexhe were the first dimensions of the PD2 subepochs were compared to quantify its dynamical measures using chaos theory (P values: 0.004 and 0.02, respectively). Note that the techniques (17). Their results (correlation dimensions, overall results of the RD analysis were indicative Kolmogorov entropies and the largest Lyapunov of fractal scaling (D < 1.5) in about 80% of all exponent), were supportive to the contention that the subepochs tested. heart rate generator evolves on a low-dimensional
  • 7. FRACTAL ORGANIZATION IN HEART RATE 373 10 I N of points round(D2)- alp-)0.50 0 N o! p- 4z m 0 | round(O2)- I N of p- 0 i I round(D2}- round(D2)- 2 H o f p- 3 H of rouncl(D2)m 4 N o f roun4(D2)- S N of roarl4(D2)- 6 N o f p- pm 246 p- Se2 pm 146 0 "k roun4(D2)- 7 X o f p - 64 round(D2)- 8 g of p,, ]. round(D2)- 9 N o f p- 0 round(D2)-20 N of p- 0 i roun4(D2)-22 N of p- 0 round(D2)-12 N of p- 0 round(D2)-13 N of p- 0 round(D2)-14 N of p- 0 round(D2)-25 N of p- 0 round(D2)-26 H of p" 0 round(D2)-17 N of p,, 0 round(D2)-28 N of p- 0 round(D2)-lg N Of p- 0 round(D2)-20 N of p- @ H of exclu sip<-0.23 2v • a 0 250 500 750 1000 1250 Fig. 3 (a) Serial pointwise dimensions (PD2s) as a function of the beat number (nref) for one of the subjects. The zero-valued PD2s are only 'sign' of the instances for which a dimensional estimate could not be derived. (b) A histogram showing the distribution of the beat number as a function of the rounded dimensional estimates. At the two extremes of the diagram we note the number of points for which a random fluctuation is supposed to take place (slope > 0.5), and on the other side the number of point for which an estimate could not be found (slope < -0.23). chaotic attractor. Later, other groups provided sup- periodic behavior was seen in normal subjects, with portive evidence to this hypothesis (18,28), although an increase in complexity during sleep (21). Recent recently Kanters et al found weak evidence in favor studies found the dimensional complexity during (19). Thus, the existence of low dimensional chaos in experimental myocardial infarction in pigs to decline cardiac activity, at least at the whole organ level of significantly prior to the occurrence of ventricular activity, is still an open question. Most of the estima- fibrillation (31). This has motivated Skinner et al tions were based on dimensional estimations of the to evaluate lethal arryhythmias in various groups of widely used Grassbeger-Procaccia algorithm. Imple- high-risk patients. It was found (with high specificity mentation of this algorithm needs several precondi- and sensitivity) that the dimensional complexity tions to be observed (29,30): an adequate choice of is reduced hours before the occurrence of lethal embedding dimension, a suitable choice of the time arrhythmias (22). delay needed to span the attractor, low level of noise Our results support the contention of low- present in the system, stationarity, and the data set dimensional chaos, as proposed by others. The corre- should not be too short. Some of these requirements lation dimension was found to vary between 3.29 are not attainable in biology and in physiology in and 5.16, with a mean of 4.01 + 0.54 (n = 10). The particular. Moreover, the G-P algorithm provides a average pointwise dimension ranged between 4.58 dimensional estimate which averages out possible and 5.88, with a mean of 5.21 + 0.41 (n = 10). Further- relevant dynamical features. Recently, the intro- more, we noticed that our subjects could be divided duction of the pointwise dimension algorithm, which into two groups according to age as follows: group 1 provides series of 'point' dimensions, has provided (21-30) years, n = 6) had a higher average, 5.49 + 0.27, some solutions to the limitations of the G-P algo- than group 2 (47-56 years, n = 4 ) at 4.79+ 0.17. rithm, namely, non-stationarity and record length. Our innovation in this study was twofold. First, we This method was implemented for heart transplant included in the dimensional complexity algorithm recipients and the dimensional complexity was found means to include both instances of low-dimensional to oscillate almost periodically (20). Also, a roughly chaos and stochastic bursts in a sequential manner,
  • 8. 374 MEDICAL HYPOTHESES 10 2O g tJL, JJl| RF' Jd l I0 10 i1. D ill I'r ,I Fig. 4 Four subepochs of sequential PD2s from the series shown in Fig. 3a. Each subepoch comprises about 150 PD2s. i.e. as a function of the beat number. Second, this cant decline in the complexity of the cardiovascular enabled us to apply a fractal technique (relative system (blood pressure and heart rate). Such findings dispersion analysis) to explore the different subepochs may reflect the breakdown and decoupling of inte- of dimension series for scale independence. We found grated physiologic regulatory systems with aging that the older group manifested fractal scaling and may signal an impairment in the cardiovascular (D < 1.5) in all subepochs tested. As for the younger ability to adapt efficiently to internal and external group, only in 64% of tested subepochs did we find perturbations. This is contradictory to the sacred fractal scaling (D < 1.5), while the rest was indicative principle of 'homeostasis', which was developed by of a random control (D > 1.5). Moreover, the differ- Walter Cannon, and postulates that with disease and ences in the averages and variances of the fractal aging the body is less able to maintain a constant dimensions between the two groups were found to steady state, as a result of breakdown of its regulatory be statistically significant. This is in contention with systems. Our findings support the chaos hypothesis of results from other chaos-derived techniques imple- a 'homeokinetic' principle in physiology, namely, mented by Kaplan et al on old versus young subjects physiological systems in young healthy subjects tend (32). They found that the older group showed signifi- to fluctuate between a set of metastable states, thus
  • 9. FRACTAL ORGANIZATIONIN HEART RATE 375 of the heart rate variability, which can be quantified 20 using fractal techniques, seems to contain 'mixing' of both chaotic and random fluctuations. The nature 10 of such a behavior is not yet understood, but one 5 may hypothesize that an increase in the dimensional complexity (D2 can be thought of as a measure --,.. of independent variables necessary to describe the 2 system), may correspond to recruitment of several 1 subsystems influencing the heart rate generator, or to the activation of more independent control loops. 0.50 A reduced complexity, on the other hand, may mani- 0.20 fest deactivation of control loops, or maybe increased self-organization of some of these systems. Also, the abrupt changes in the dimensional complexity may 0.10 represent shifts between different attractors of the system. Such hypotheses, may better be resolved by 140 74 37 19 10 5 3 comparing the fractal dimensions of the dimensional Fig. 5 Plot of RD% (relative dispersion) versus interval length on complexity (and other measures of nonlinear tech- a logarithmic scale. The fractal dimension (D) is derived from the niques) under different physiological and clinico- slope (slope = l-D). pathological settings. Currently, we are in the process of obtaining longer data records from heart transplant recipients, in order making the system more adaptable to its internal and to gain more insight regarding the value of the fractal external surroundings (15,33). estimate of the dimensional complexity of the heart We thus propose that the dimensional complexity rate generator, as a potential new dynamical measure. T a b l e 2 Subepochs o f pointwise dimension (PD2) series, averaged P D 2 s for each subepoch, fractal dimension (D) for each subepoch, and averaged P D 2 s for w h o l e records Gender Age Nref PD2 ± SD average over subepochs D(RD) ± SD PD2 ± SD average over total record M 21 1-150 5.28 ± 0.88 1.42 + 0.07 5.37 ± 0.93 300--450 5.09 ± 0.09 1.27 + 0.03 570-720 5.61 ± 0.73 1.49 ± 0.06 850-1000 4.35 ± 0.69 1.09 ± 0.04 F 25 1-90 4.45 ± 1.05 1.21 ± 0.09 5.19 ± 1.04 200-350 4.86 + 0.75 1.54 ± 0.06 M 26 130-196 6.01 ± 0.97 1.72 ± 0.11 5.83 ± 1.02 250-850 5.62 ± 0.97 1.19 ± 0.10 F 28 1-300 5.90 ± 0.90 L28 + 0.09 5.34 ± 0.72 301--600 5.03 ± 0.35 1.36 ± 0.12 M 30 1-200 4.91 ± 0.69 1.55 ± 0.09 5.30 ± 0.11 600--995 5.09 ± 1.10 1.13 ± 0.06 M 30 30-110 5.92 ± 0.83 1.57 ± 0.09 5.88 ± 1.08 125-295 5.34 ± 0.82 1.63 ± 0.09 M 47 1-350 3.92 ± 0.51 1.11 ± 0.04 4.69 ± 0,77 400-1250 4.99 ± 0,63 1.21 ± 0.06 M 56 1-300 4.95 ± 0,68 1.18 ± 0.07 5.03 ± 0,71 500-1000 5.11 ± 0.69 1.32 ± 0.05 F 56 100-300 4.63 ± 0.72 1.24 ± 0.07 4.87 ± 0.96 500-750 4.32 ± 1.21 1.09 ± 0.05 F 56 1-80 4.39 ± 0.69 1.33 ± 0.08 4.58 ± 0.64 200-380 4.63 ± 0.79 1.14 ± 0.08 mean ± SD 5.02 ± 0.54 1.32 ± 0.18 5.21 ± 0.41 M, male; F, female; Nref, sequences of consecutive data points' subepochs; PD2 + SD, averaged pointwise dimension + standard deviation; D(RD), fractal dimension of each subepoch, derived from relative dispersion analysis.
  • 10. 376 MEDICAL HYPOTHESES References 15. Lipsitz L A. Age-related changes in the 'complexity' of cardiovascular dynamics: a potential marker of vulnerability to 1. Appel M L, Berger R D, Saul J P, Smith J M, Cohen R J. Beat disease. Chaos 1995; 5(1): 102-109. to beat variability in cardiovascular variables: noise or music? 16. Kobayashi M, Musha T. 1/f fluctuation of heartbeat period. J Am Coil Cardiol 1989; 14:1139-1148. IEEE Trans Biomed Eng 1982; 29: 456-457. 2. Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular 17. Babloyantz A, Destexhe A. Is the normal heart a periodic neural regulation explored in the frequency domain. Circula- oscillator. Biol Cybernetics 1988; 58:203-211. tion 1992; 84: 482-492. 18. Rigney D R, Mielus J E, Goldberger A L. Is normal sinus 3. Malliani A, Pagani M, Lombardi F. Physiology and clinical rhythm 'chaotic'? measurement of Lyapunov exponents. implications of variability of cardiovascular parameters with Circulation 1990; 82(4) Suppl. III, abstr. focus on heart rate and blood pressure. Am J Cardiol 1994; 19. Kanters J K, Holstein-Rathlou N-H, Agner E. Lack of 73: 3C-9C. evidence for low-dimensional chaos in heart rate variability. 4. Akselrod S, Gordon D, Ubel F A, Shannon D C, Barger A C, J Cardiovasc Electrophysiol 1994; 5: 591-601. Cohen R J. Power spectrum analysis of heart rate fluctuations: 20. Zbilut J P, Mayer-Kress G, Giest K. Dimensional analysis of a quantitative probe of beat-to-beat cardiovascular control. heart rate transplant recipients. Math Biosci 1988; 90: 40-70. Science 1981; 213: 220-222. 21. Mayer-Kress G, Yates F E, Benton L et al. Dimensional 5. Saul J P, Arai Y, Breger R D, Lilly L S, Colucci W S, Cohen analysis of nonlinear oscillations in brain, heart, and muscle. R J. Assessment of autonomic regulation in chronic congestive Math Biosci 1988; 90: 155-182. heart failure by heart rate spectral analysis. Am J Cardiol 1988; 22. Skinner J E, Pratt C M, Vybrial T. A reduction in the correla- 61: 1292-1299. tion dimension heartbeat intervals precedes imminent ventricular 6. Pomeranz B, Macaulay R J B, Caudill M A e t al. Assessment fibrillation in human subjects. Am Heart J 1993; 125: 731-743. of autonomic function in humans by heart rate spectral 23. Rand D, Young L-S, eds. Detecting strange attractors in fluid analysis. Am J Physiol 1985; 248 (Heart Circ Physiol 17): turbulence. In: Dynamical Systems and Turbulence. Berlin: H151-H153. Springer-Verlag, 1981. 7. Madwed J B, Snads K E F, Saul J P, Cojen R J. Spectral 24. Grassberger P, Procaccia I. Measuring the strangeness of analysis of beat-to-beat variability in HR and ABP during strange attractors. Physica 1983; 9D: 183-208. hemorrhage and aortic constriction. In: Lown B, Malliani A, 25. Glenny R W, Robertson H T, Yamashiro S, Bassinghwaighte. Prodocimi M, eds. Neural Mechanisms and Cardiovascular Applications of fractal analysis to physiology. J Appl Physiol Disease. Fidia Research Series. Padova: Liviana Press, 1986, 1991; 70(6): 2351-2367. Vol. 5: 291-301. 26. Mandelbrot B B. Thc Fractal Geometry of Nature. San 8. Takase B, Kurita A, Noritake Met al. Heart rate variability in Francisco: W H Freeman, 1982. patients with diabetes mellitus, ischemic heart disease, and 27. West B J. Fractal Physiology and Chaos in Medicine. New congestive heart failure. J Electrocardiol 1992; 25: 79-88. Jersey: World Scientific, 1990. 9. Kleiger R E, Miller J P, Bigger J T, Moss A J, and the Multi- 28. Ravelli F, Andolini R. Complex dynamics underlying the center Post-infarction Research Group. Decreased heart rate human electrocardiogram. Biol Cyb 1992: 67; 57. variability and its association with increased mortality after 29. Kantz H, Schreiber T. Dimension estimates and physiological acute myocardial infarction. Am J Cardiol 1987; 59: 256-262. data. Chaos 1995; 5(1): 143-154. 10. Ott E. Chaos in Dynamical Systems. Cambridge: Cambridge 30. Schreiber T, Kantz H. Noise in chaotic data: diagnosis and University Press, 1993. treatment. Chaos 1995; 5(1): 133-142. 11. Olsen L F, Degn H. Chaos in biological systems. Quarterly 31. Skinner J E, Carpeggiani C, Landisman C E, Fulton K W. Rev Biophys 1985; 10(2): 165-221. Correlation dimension of hcartbeat intervals is reduced in 12. Goldberger A L, Rigney D R, West B J. Chaos and fractals conscious pigs by myocardial ischemia. Circulation Res 1991; in human physiology. Sci Am 1990; 262: 42--49. 68: 966-976. 13. Goldberger A L, West B J. Fractals in physiology and 32. Kaplan D T, Furman M 1, Pincus S M, Ryan S M, Lipsitz L A. medicine. Yale J Biol Med 1987; 60: 421-435. Aging and the complexity of cardiovascular dynamics. Bioph 14. Goldberger A L. Nonlinear dynamics, fractals and chaos: J 1991; 59: 945-949. applications to cardiac electrophysiology. Ann Biomed Eng 33. Lipsitz L A, Goldberger A L. Loss of 'complexity' and aging. 1990; 18: 195-198. J Am Med Assoc 1992; 267: 1806-1809.