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Spectral Analysis of Cardiovascular Parameters of Rats Under Irregular Light-Dark Regime

Authors:
MEASUREMENT 2011
Proceedings of the
8th International Conference on Measurement
Congress center of the Slovak Academy of Sciences
April 27-30, 2011, Smolenice Castle, Slovakia
MEASUREMENT 2011
Copyright 2011 by Institute of Measurement Science, SAS
Editors: Ján Maňka, Viktor Witkovský, Milan Tyšler, Ivan Frollo
Publisher: Institute of Measurement Science
Slovak Academy of Sciences
Dúbravská cesta 9, 841 04 Bratislava
ISBN 978 - 80 - 969 - 672 - 4 - 7
Printed in Slovakia
by VEDA, Publishing House of the Slovak Academy of Sciences
Cover page aerial photo: courtesy of Andrej Kuruc, Bratislava
MEASUREMENT 2011, Proceedings of the 8th International Conference, Smolenice, Slovakia
343
Spectral Analysis of Cardiovascular Parameters of Rats Under Irregular
Light-Dark Regime
1M. Teplan, 2L. Molčan, 2M. Zeman
1Institute of Measurement Science, Slovak Academy of Sciences,
Bratislava, Slovak republic,
2Department of Animal Physiology and Ethology, Faculty of Natural Sciences,
Comenius University Bratislava, Slovak republic
Email: michal.teplan@savba.sk
Abstract.
Our study is related to shift work that possibly brings negative consequences on public health.
Adaptation of cardiovascular parameters in rats to rotating phase delay shift in light regime
was addressed. Prolongation of circadian rhythms was observed for blood pressures, heart
rate and locomotive activity. Relative amount of circadian in comparison to ultradian rhythms
was strongly activated by shifted regime in its first weeks, while being the lowest during
persistent light conditions. Results contribute to understanding of physiological changes that
accompany shift work.
Keywords: spectral analysis, Lomb-Scargle periodogram, unevenly sampled data
1. Introduction
Work connected with shifted day regime is a common feature of modern society. However, it
can alter biological rhythms in humans. Chronic disturbances of biological clocks results in
the suppression of circadian rhythms with possible negative consequences on the
cardiovascular, neuroendocrine and gastrointestinal system. Such regime can contribute to the
development of many neurological, cardiovascular [1] and cancer diseases [2].
In epidemiologic studies many factors are usually simultaneously involved, thus they can
hardly elucidate all negative effects of shift work on physiologic parameters or reveal hidden
causal interrelationships. Moreover, results of epidemiological studies linking shift work and
various health risk factors often claim opposite effects. Therefore it is the advantage of animal
model with treatment under controlled conditions, which can analyze different factors
separately. Experimental studies using animal models are needed for better understanding of
biological mechanisms of endogenous biological clocks and the way how they control variety
of body functions.
Biological clocks control physiological and behavioural processes in all organisms, including
humans. Regular synchronization is a necessary prerequisite for their normal function. Light
is the most significant stimulus for resetting biological clocks in higher vertebrates [3]. The
light signal is transferred from the retina to the central oscillator via the retinohypothalamic
tract. In the central oscillator a rhythmic, circadian, transcription of clock genes occurs and
the signal is transferred by output pathways into all organs of the body. In this work we
assessed effects of light regime as the main factor, which can affect the central oscillator, on
the control of cardiovascular system of rats.
The aim of this study was to analyze the effect of irregular light-dark regime on endogenous
circadian and ultradian rhythms of selected physiological parameters in rats. In this part of the
work cardiovascular parameters and locomotive activity are addressed. In particular, we
MEASUREMENT 2011, Proceedings of the 8th International Conference, Smolenice, Slovakia
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investigated how rotating phase delay shifts impact rhythmic changes of systolic and diastolic
blood pressure (SP and DP), hearth rate (HR) and locomotive activity (LA) of rats.
2. Subject and Methods
Cardiovascular and locomotive variables were measured telemetrically using the telemetric
sensor TA 11 PA-C40 (DSI St. Paul, Minnesota, USA). Monitoring begun two weeks after
the surgical implantation of sensors into the abdominal aorta of 4 female normotensive rat
(Rattus norvegicus,12 month old of the beginning of the experiment). During a time span of
18 weeks the rats were exposed to the following set of conditions: control 12:12 light/dark
(LD) for a period of one week; phase delay shifts of light-dark regime by eight hours every
second day (Shift) for a period of 12 weeks; again LD 12:12 regime for one week; and finally
continuous light (LL) for the last 4 weeks. The particular Shift conditions aimed to simulate
light/dark conditions of shift work on fast rotation program. As the dark phase was prolonged
by 8 h every second day, it is the most common shift work. Further details on experimental
design, technical and animal treatment can be found in [4].
Measured variables were recorded every 10 s, stored in PC by program A.R.T Gold 4.1 (DSI,
St. Paul, Minnesota, USA). Permanent and wireless data acquisition enabled on-line
monitoring of recording variables in order to control overall functioning of the recording
system and animal conditions. For further data control and preprocessing manipulation
Microsoft Excel and MatLab programs were used.
For spectral analysis modified Lomb-Scargle periodogram (LSP) [5] was adapted in MatLab
environment (MatLab 2008b, MathWorks, Inc. USA). LSP approach is identical with
estimation of harmonic contend of a data set at a given frequency by linear least-squares
fitting to the model. This method has several advantages in comparison with traditional fitting
techniques. The basic characteristic of our large data sets was the absence of regular sampling
in recorded signal. Several reasons contributed to these irregularities: Manual weighting of
the experimental animals, when wireless communication of the sensor with receiving plate
was interrupted for a few minutes. Also occasional shorter malfunction of the recording
system were involved. Still, our task was not to discard the data recorded for a number of
days but rather to apply methods of analysis that are capable to deal with unevenly sampled
data. Traditional spectral estimators need to modify irregularly sampled series by
interpolation and even re-sampling. Unlike conventional Fourier analysis, LSP approach is
capable to overcome dropout of smaller data fractions in time series. Another advantage of
LSP approach is a possible choice of arbitrarily fine frequency step and examination of
frequencies higher than the mean Nyquist frequency. Moreover, weighting of single power
points occurs rather on a ‘per point’ basis instead of on a ‘per frequency interval’ basis. This
means that the height of the peak is stable unlike in the case of Fourier types of analysis
where height of a peak is confined with frequency step. As all other methods in the search for
periodic signals, the LSP requires the assumption of independent Gaussian noise on the error
term. Under this assumption one can estimate level of significance of resulting peaks. Peaks
probability distribution is evaluated according to observance of certain amount of
independent peaks. Basically, the LS algorithm is quite time demanding, however several less
time consuming modifications with sufficiently exact approximation were developed,
working at the level of N-logN computational time demand (N is a number of frequency
components to be estimated).
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3. Results and discussion
Spectra obtained by LSP approach reveal animal reactions to different regime conditions. In
our analysis we focus on circadian (20-30 h) and ultradian (2-6) rhythms. Strength and period
localization of power peaks in these ranges was changing (Fig.1) according to the conditions.
While during LL conditions circadian contribution is highly suppressed, during Shift
conditions 24 h peak is elongated to longer periods.
1102 5 24 50
200
400
600
800
period (hour)
power
1102 5 24 50
200
400
600
800
period (hour)
power
1102 5 24 50
200
400
600
800
period (hour)
power
24.4 h 28.7 h
shifted light/darklight/lightlight/dark b) c)
a)
Fig. 1: Periodogram calculated by LSP approach for diastolic pressure of rat #1 for 3 different conditions: a)
12:12 light/dark revealing circadian peak near 24 h, b) persisting light conditions with emphasized activity of
ultradian rhythms, and c) delayed shift in light/dark conditions with prolongation of circadian rhythm.
0
1
2
3
4
5
shift in period [hour]
shift: week 1 week 2 week 3 week 4 week 5 week 12 LD LL: week 1
systolic pressure
diastolic pressure
heart rate
locomotive activity
Fig. 2. Drift of main circadian periods from 24 h period represented by zero value on Y-axis. X-items represent
week intervals under shift, light/dark and light/light regime. Mean data from all rats with standard
deviations in a form of error bars are presented.
In Fig.2 the shift of circadian peak of 24 h is evaluated. The strongest drift occurred during
the second and 12th week of the Shift conditions, suggesting more complex adaptation
mechanisms of inner clocks. Initial wave of adaptation was weakened during the next weeks.
Unfortunately, during week 6-11 no telemetry measurements were performed. Increased shift
of SP and DP during LD conditions could be affected by tightly preceding of Shift conditions,
while HR and LA seemed to be more flexible according to their reaction in this particular
time point of the experiment. Whereas from the point of view of Fig.2 there were two
MEASUREMENT 2011, Proceedings of the 8th International Conference, Smolenice, Slovakia
346
vertexes in deviation of 24 h peak in Shift week no. 2 and 12, in Fig.3 there is substantial
difference between these 2 weeks. Relative amount of LSP power from circadian range in
comparison to the amount of power in ultradian range was more strongly activated only in the
first and second week of Shift regime. During the last two weeks of persistent light conditions
circadian rhythms were relatively eliminated in the highest extend.
10
20
30
power ratio
shift:week1 week2 week3 week4 week5 week6 week12 LD LL:week1 week3 week4
systolic pressure
diastolic pressure
heart rate
locomotive activity
Fig. 3: Ratio of the power between circadian band (20-30 h) and ultradian band (2-6 h) during different regime
conditions. X-items represent week intervals under shift, light/dark and light/light regime. Mean data from all
rats with standard deviations in a form of error bars are presented.
We showed that the cardiovascular system of rats (blood pressure, heart rate) is able to adapt
to delay shifts in light regime by lengthening of endogenous period of cardiovascular
parameters. Moreover, ratio of circadian and ultradian cycles is changing. Results contribute
to understanding of physiological changes that accompany shift work. In further work shifted
regime in opposite – advanced direction will be spectrally analyzed.
Acknowledgements
This work was supported by Slovak Grant Agency for Science (grant VEGA No 2/0019/10
and APVV-0214-07).
References
[1] Knutsson A. Health disorders of shift workers, Occup Med (Lond), 53:103-108, 2003.
[2] Davis S., Mirick D.K. Circadian disruption, shift work and the risk of cancer, Cancer
Causes Control, 17:539-545, 2006.
[3] Boivin, D.B., James, F.O. Light treatment and circadian adaptation to shift work, Ind.
Health, 43:34-48, 2005.
[4] Molčan, L. Effect of lightning regimen simulating shift work on rhytmic changes in the
cardiovascular system and its regulation, Master thesis, Comenius University in
Bratislava, Faculty of Natural Sciences, Dep. of Animal Physiology and Ethology, 2010.
[5] Press, W.H., Teukolsky, S. Numerical recipes in C: The art of scientific computing.
Cambridge University Press, 1992, 575-583.
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