Download Thermoregulation and Heart Rate Variability

Clinical Science (1996) 90. 97-103 (Printed in Great Britain)
97
Thermoregulation and heart rate variability
Lee A. FLEISHER, Steven M. FRANK, Daniel I. SESSLER, Christi CHENG, Takashi MATSUKAWA
and Carole A. VANNIER
Departments of Anaesthesiology and Critical Care Medicine and Medicine, Johns Hopkins
University School of Medicine, Baltimore, Maryland, U.S.A., and the Thermoregulation Research
Laboratory, Department of Anaesthesia, University of California, San Francisco, U.S.A.
(Received 10 Augustfl8 October 1995; accepted 24 October 1995)
1. Heart rate variability is modulated by multiple
control systems, including autonomic and hormonal
systems. Long-term variability, Le, the very lowfrequency band of the power spectra, has been postulated to reflect thermoregulatory vasomotor control,
based upon thermal entrainment experiments. However, the relationship between thermoregulatory responses (vasoconstriction and shivering) and heart
rate variability has not been studied.
2. We performed two distinct protocols in a series of
human subjects. In the first protocol, core temperature was reduced by intravenous infusion of cold
saline, while skin temperature was unchanged. The
second protocol involved skin-surface warming and
cooling until shivering developed. Power spectral
analysis was performed using a fast Fourier transformation, and the area in three distinct band-widths
was determined.
3. Very low-frequency power (0.0039-0.04 Hz)
increased significantly in response to core cooling,
peripheral vasoconstriction and sbivering, wbile botb
very low- and low- (0.04-0.15 Hz) frequency power
increased in response to skin-surface cooling. Heart
rate decreased during core cooling-induced vasoconstriction, suggesting a direct tbermal response,
and increased in relation to the metabolic demands
associated with shivering.
4. Our results suggest tbat very low-frequency power
is modulated by tbermal stimuli wbicb result in core
hypothermia and thermoregulatory activity, wbile
skin-surface cooling witbout core bypothermia does
not selectively modulate this frequency band.
INTRODUCTION
Heart rate is controlled by the interaction of
multiple homoeostatic mechanisms [1-3]. The
presence of beat-to-beat or heart rate variability
(HRV) has been associated with cardiovascular
health [4]. In contrast, lack of variability has been
associated with morbid events [5-7]. Heart rate
pattern can be evaluated. by multiple methods,
including the use of Fourier analysis, and three
distinct frequency bands can be recognized: (i) the
high-frequency peak, centred around 0.2 Hz, (ii) the
low-frequency peak, centred around 0.1 Hz, and (iii)
the very low-frequency band, described as the power
between 0.0039 and 0.04 Hz [5]. Several investigators have proposed that discrete frequency components of HRV correlate with different components
of the autonomic nervous system [2, 3, 8]. In
general, short-term HRV (high frequency) is thought
to be controlled by the parasympathetic nervous
system, while intermediate variability (low frequency) is under the control of the sympathetic and
parasympathetic systems, and may reflect the
activity of Mayer waves [2]. The ratio of low/highfrequency power has been proposed as a measure of
sympathovagal balance [9]. Control of long-term
variability (very low frequency) is less well described, but is thought to reflect an interaction of
the renin-angiotensin system and thermoregulatory
vasomotor control [8, 10-12]
The physiological importance of the very lowfrequency range remains unclear. The natural contractile oscillations of the smooth muscle of the
peripheral vascular bed undergo spontaneous fluctuations with a periodicity of 10s [13]. It has been
demonstrated that the oscillations of cutaneous
blood flow can be synchronized to skin or vascular
blood temperature. Kitney and co-workers [II, 12,
14] demonstrated thermal entrainment of the very
low-frequency power of both blood pressure and
HR V to the frequency of alteration of a subject's
hand in warm and cold water baths. However, the
hypothesis that thermal synchronization of blood
flow and heart rate occurs with oscillation of cutaneous skin temperature has not been uniformly
accepted [15]. Additionally, thermal entrainment. at
frequencies between 0.01 and 0.1 Hz (encompassmg
both the very low- and low-frequency band) predominantly increased the 0.10 Hz periodic HRV;
however, the 0.01-0.12 Hz frequency band oscillations did not increase significantly [16]. Therefore,
the basis for a thermoregulatory component to the
very low-frequency HRV power remains controversial.
Key words: electrocardiography, heart rate variability. hypothermia. measurement, spectral analysis. thermoregulation.
Abbreviation: HRV, heart rate variability.
Correspondence: Dr L. A. Fleisher. The Johns Hopkins Hospital. 600 N. Wolfe Street, Carnegie ....2 Baltimore. MD 21287, U.S.A.
98
L. A. Fleisher et 31.
Although the above studies evaluated the effect of
external temperature entrainment on HRV, no study
directly evaluated the relationship of HRV to activation of thermoregulatory responses. We hypothesized that if thermoregulation was related to the
very low-frequency component of HRV then it
would be related to thermoregulatory vasoconstriction during core hypothermia and not to peripheral
cold stimulus, which has a much less significant
effect on thermoregulation [17]. To determine the
influence of thermoregulation on HRV, we studied
human volunteers subjected to different types of
cold challenge. These stimuli included the effects of
two methods of systemic warming and cooling
sufficient to provoke sweating, vasoconstriction and
shivering.
METHODS AND MATERIALS
Volunteers were studied under two circumstances,
as part of a larger study of anaesthetics and thermoregulatory changes [17]. The first protocol reduced
core temperature while maintaining constant skin
temperatures, while the second reduced both skin
and core temperatures. Since respiratory rate can
affect the frequency of the 'parasympathetic' band,
as well as influence the power in all frequency
bands, we measured respiratory rate in order to
ensure that it was greater than 12 breaths/min in all
protocols [18].
Protocol I: core cooling
With approval from the Committee on Human
Research at the University of California, San
Francisco, we studied six male volunteers between
the ages of 25 and 35 years. These volunteers were
not conditioned athletes. None was obese, taking
medication or had a history of thyroid disease.
The volunteers were advised to eat lightly before
arriving at the laboratory. They were minimally
clothed during the protocol and rested supine on a
standard operating room table. A 16-g catheter was
inserted into the superior vena cava via the right
internal jugular vein. A circulating-water mattress
and forced-air cover were used to maintain skin
temperature (weighted average of 15 sites) between
32 and 34C. However, mean skin temperature in
individual volunteers was nearly constant throughout the study.
Volunteers were then cooled by central venous
infusion of lactated Ringer's solution at 3°e, as
previously described [19, 20]. The solution was
cooled by passing it through an aluminium cardiopulmonary bypass heat exchanger immersed in an
ice-and-water slurry. The rate of infusion was
initially 10 ml/rnin and was adjusted at I-min intervals to maintain a core cooling rate near 1.6'C/h.
Core cooling was continued until sustained shivering was identified (approximately 1.5-2.51). Respira-
tory rate did not significantly change during the
course of the study.
Protocol 2: skin surface cooling
With approval from the Committee on Human
Research at the University of California, San
Francisco, five male volunteers were studied. As in
protocol I, these volunteers were not conditioned
athletes. None was obese, taking medication or had
a history of thyroid disease.
The volunteers were advised to eat lightly before
arriving at the laboratory. They were minimally
clothed during the protocol and rested supine on a
standard operating room table. Mean skin temperature was initially increased to 37°C by a circulatingwater mattress and forced-air warmer. After sweating was observed, the temperature of the circulatingwater mattress and forced-air cover was gradually
decreased until vasoconstriction and then shivering
were triggered. Respiratory rate did not significantly
change during the course of the study
Measurements (for both protocols)
Core temperature was measured in the distal
oesophagus using disposable Mon-a-Therm thermocouple probes (Mallinckrodt Medical, Inc., St Louis,
MO, U.S.A.). Optimal insertion length of the
oesophageal probe was calculated using the formula
of Mekjavic and Rempel [21]. The aural probes
were inserted by the volunteers until they felt the
thermocouple touch the tympanic membrane;
appropriate placement was confirmed when the
volunteers easily detected a gentle rubbing of the
attached wire. The probe was then securely taped
in place, the aural canal occluded with cotton and
a gauze bandage positioned over the external ear.
We have previously demonstrated that distal
oesophageal and tympanic membrane temperatures
are virtually identical under the circumstances of
this study [22].
Sweating was continuously quantified on the left
upper chest using a ventilated capsule. A sustained
sweating > 40 g h ~ 1 m ~ 2 was considered significant.
Vasoconstriction was monitored using forearm
minus fingertip skin-temperature gradients. This
measure correlates well with absolute finger blood
flow as determined by volume plethysmography
[23]. As in previous investigations, a gradient
exceeding 4"C identified significant vasoconstriction
[23, 24]
Shivering was evaluated using oxygen consumption (Deltatrac; SensorMedics Corp., Yorba Linda,
CA, U.S.A.). The system was used in canopy-mode,
and measurements were averaged over I-min intervals and recorded every 5 min. A sustained 30%
increase in oxygen consumption identified significant
shivering; this increase was identified by an observer
blinded to treatment, as well as core and skin
temperatures. The core temperatures triggering sig-
Thermoregulation and R-R variability
nificant sweating, vasoconstriction and shivering
identified the thresholds for each response.
Power spectral analysis
VO.lunteers were monitored by a calibrated
amplitude-modulated AECG monitor (SpaceLabs
ambulatory ECG model 90205. Redmond, WA,
U.S.A.) with modified bipolar lead V5 and modified
bipolar lead VI or V3. The AECG recordings were
analysed at the end of the monitoring period using
lead V5 on a computerized analysis system (SpaceLabs FT3000a). The peak of the QRS was identified
for each beat by a computer algorithm and beat
identification was confirmed by an investigator,
Those periods in which beat identification was poor
were excluded from the analysis. Hour-long files
containing successive R-R intervals were created.
Shiver~ng did not interfere with the ability of the
analysis system to accurately identify the QRS peak
and determine R-R interval length.
The power spectral density for representative R-R
in~erval series was determined by investigators
blinded to temperature. A series of R-R intervals
were reviewed visually for R-wave determination
and ectopic beats. Each series contained fewer than
five ectopic beats. The intervals surrounding ectopic
beats were removed and the average R-R interval
for the previous three beats was inserted to
eliminate the effects of ectopy on the Fourier
transformation.
The method of analysis of the power spectrum
was adapted from Berger et al. [25]. Initially, the
time series of interest was reviewed to ensure
stationariness. Fourier time-series analysis requires
evenly spaced values. Therefore, the R-R interval
data were plotted as a function of length in milliseconds and resampled at 4 Hz (using a cubic spline
function) to obtain an evenly spaced series of 4 min
of instantaneous heart rates (four instantaneous
heart rates per second). The mean heart rate was
then subtracted and a Hanning window was
applied.
Po.wer spectral density plots were obtained by
plotting the square of the amplitude of the fast
Fourier transformation of the time series against
frequency (Hz) for both 4 and 15min datasets
during a 15min steady-state period of core temperature and after each of the thresholds of sweating,
shivering and vasoconstriction were reached (SpaceLabs FT3000a analysis system and MatLab 4.0 for
Macintosh). Power (ms 2/band-width) in high frequency (0.125-0.5 Hz) and low frequency (0.05-0.125
Hz) was determined by integrating the area under
the power spectral density plots for the initial 4min-long datasets for each study period. Power in
the very low-frequency (0.0039-0.05 Hz) band was
determined by integrating the area under the power
spectral density plots for the 15-min-long datasets
for protocols I and 2, since analysis of very lowfrequency power requires longer datasets. The coeffi-
dent
lated
since
HRV
99
of variance for each 15min series was calcuby dividing the SD by the mean R-R interval
it has been suggested as a means of assessing
independent of heart rate.
Statistical analysis
The results of core temperature, heart rate and
of HRV are expressed as meant
SEM . .olfferenc~s over time were determined using
analysis of vanance for repeated measures with
P <0.05 considered significant (SuperAnova v1.11,
Abacus Concepts). Differences between two time
pe~iods within. one group were compared using a
paired t-test WIth P < 0.05 considered significant.
measure~ents
RESULTS
Protocol I: core cooling
The core temperature thresholds for vasoconstriction
and
shivering were 36.6 ± 0.2°C and
36.1 ± 0.1DC, respectively (Fig. 1). Heart rate was
67 ± 3 beats/min at baseline, decreased significantly
with vasoconstriction (63 ± 3 beats/min, P < 0.01)
and then increased significantly over baseline with
the onset of shivering (72 ± 4 beats/min, P < 0.05).
The coefficient of variance was 0.074+0.008 at
baseline, 0.089 ± 0.009 with vasoconstriction and
~.126±0.013
with shivering and significantly
increased overall (P < 0.05). However, it did not
significantly increase between each temperature
phase, i.e. from baseline to vasoconstriction or
vasoconstriction to shivering. Very low-frequ~ncy
power increased significantly at the time vasoconstricti?n .occurred (P < 0.05), and was higher
w~en shivering was observed (P not significant)
(FIg. 2). Low-frequency power remained unchanged
with
vasoconstriction
and
increased
nonsignificantly with shivering (P = 0.13). Highfrequency power remained relatively constant over
the temperature ranges evaluated in the protocol.
The ratio of low/high-frequency power was
unchanged with vasoconstriction and increased with
borderline significance with shivering (P = 0.055)
(Fig. 3). When the time series were evaluated, long
duration oscillations (2 min) were greater during
vasoconstriction (Fig. 4).
Protocol 2: skin-surface cooling
Sweating occurred when body temperature
increased O.5°C from baseline values. Thermoregulatory vasoconstriction occurred at a core temperature of 37.1 ±O.I°C and skin temperature of
33.0±0.4°C (Fig. 1). Shivering occurred at a core
temperature of 37.1 ± 0.1°C and skin temperature of
29.9 ±0.4°C. Heart rate was 68 ±7 beats/min at
baseline, increased to 78 ± 7 beats/min with sweating
and returned to near-baseline with vasoconstriction
L. A. Fleisher et al.
100
38~ (a)
37
36
~
II
~7000
a
E
~6000
~
I
U 35
::0
0000
Core
temperature
&.5000
t;5-4000
].4
~a. 33
~32
f3000
.22000
t-
~ 1000
31
0
0000
30
-.....,r-------r-----""T"'--
29.....
8aseline
Vasoconstriction
Shivering
N'
38
(b)
Core
temperature
37
36
~ 35
7000
.
!-6000
l5000
t;5::0 -4000
...,..
.:;: 3000
~
0
~ H
--' 2000
133
1000
0000
5 32
l--
31
30
29 ......-.,....---.,r----~---_r-Sweating Vasoconstriction Shivering
8aseline
N'
7000
.§.6000
5000
it;--4000
..
<:
~3000
Fig. I. Core temperature changes associated with core cooling (~,
protocol I) and skilHurfacf cooling (b, protocol 2). Core coaling was
associated with a significant decrease in core temperature at the onset of
vasoconstriction and shivering. Skin-surface temperature was unchanged.
Skin-surface cooling was associated with a significant increase in skin
temperature with sweating. and a Significant decrease when shivering
occurred. Core temperature was unchanged. Statistical significance:
'p < 0.05 compared with baseline.
(63 ± 5 beats/min) and shivering (60 ± 4 beats/min).
The coefficient of variance was 0.078 ± 0.0 18 at
baseline, 0.072 ± 0.009 with sweating, 0.102 ± 0.013
with vasoconstriction and 0.119 ± 0.021 with shivering and significantly increased overall (P < 0.0 I). The
only discrete period during which the coefficient
increased significantly was from sweating to vasoconstriction (P < 0.0 I). Power in all frequency bands
decreased in value between baseline and sweating.
Very low-frequency power did not change significantly during sweating nor increase significantly
from baseline with either vasoconstriction or shivering (Fig. 5). Neither the ratio of low/high-frequency
power nor high-frequency power changed significantly between the different states. Low frequency
increased between baseline and vasoconstriction
(P=0.055) and increased significantly with shivering
(P < 0.05) When power values in the frequency
bands during vasoconstriction and shivering were
compared with those during sweating, both very
low-frequency and low-frequency power were shown
to increase significantly.
~
-i.2000
:f
1000
I
I
Baseline
Vasoconstriction
Shivering
Fig. 2. Power in the very low-, low- and high-frequency bands
associated with core cooling by infusion of coldsaline.Thermoregulatory vasoconstriction was associated with a significant increase in very
low-frequency power. Statistical Significance: 'P < 0.05 compared with
baseline.
DISCUSSION
As opposed to the work described previously, we
evaluated the thermoregulatory response effects on
the power spectra by independently manipulating
core and skin temperature. Core cooling, which
triggered thermoregulatory vasoconstriction, selectively increased power in the very low-frequency
band, which was associated with no change in the
ratio of low/high power and a significant decrease in
average heart rate. In contrast, peripheral cooling
selectively increased power in the low-frequency
band, with no significant change in power in the
very low-frequency band or in heart rate. These
findings suggest that the change in particular frequency bands of the power spectra depends upon
the mode of thermoregulatory challenge, and not
thermoregulation per se.
Thermoregulation and R-R variability
8 (0)
.§
101
8000
t
i 7000
t6000
7
6
l5000
~5
~
f ..
e-
f~
f3000
ii.fOOO
~
-2000
I
-..,..----1""""'----.--Baseline
Vasoconstriction
Shivering
$'000
0..L.........,r----~--....,.--......,..._-
0 ...
8000
t
7000
8
.S!
•
16000
(b)
[5000
7
t-.fOOO
c
i! 6
~ 5
r~3000
2000
1
~ 1000
~
f ..
::!;
f~
0 ...........,...------......- - - - 8000 -
I
7000
0 ...._ - - -......- - - . - - - _ _ .......Baseline
Sweating Vasoconstriction Shivering
Fia. 3. The ratio of low/hi......requency power for core coolllll (.)
and skllHUrface coolllll (b). The ratio increased with borderline signifIcance with sweating during core hypothermia (/'= 0.055), while no change
was observed with skilHurface cooling.
!:6OOO
[5000
~.fOOO
~3000
f
1..2000
:f
1000
o .....__.......--~--....,.--......,..._Baseline
1200
R-R interval
(ms)
1000
800
rw"WIII'Mrul...,.~
...'l,I.lw.M.."\R~AlJI,I.Wd.
1200
R-R interval
(ms)
1000
Sweating
Vasoconstriction
Shivering
Fla. 5. Power In the very low-, low- and hl......requency bands
associated with skllHUrface coolllll. Shivering was associated with
significant increases in low-frequency power. but not very low-frequency
power. When compared with the lower power observed during sweating,
both very low- and low-frequency power increased significantly. Statistical
significance: '/' < 0.05 compared with baseline, tP < 0.05 compared with
sweating.
800
Beat number
Fla. 4.Two representatlYe R-R time series of 10 min duration from
one volunteer In protocol I. An increase in the amplitude and components of HRV, particularly long-term oscillations, can be noted from
baseline (0) to a period ofcore hypothermia and cutaneous vasoconstriction
(b). R-R interval duration significantly increased from 905 ± 57 (SO) ms at
baseline to 1027 ± 81 ms with vasoconstriction.
Several investigators have suggested that thermoregulatory control systems alter arterial blood pressure, causing spontaneous oscillations characteristic
of non-linear systems [8, 26]. Such systems are
subject to selective entrainment, whereby the oscillatory frequency changes in response to an applied
stimulus. Hyndman et al. [13] applied a thermal
stimulus by placing one hand alternately in two
different temperature baths, with the frequency con-
sidered as the time in the bath for a complete cycle.
When the stimulus was varied in the range of 8 to
120s, the heart rate and blood pressure power
spectrum showed a dominant peak at the stimulus
frequency, which is different from the peak observed
in the spontaneous situation. When the stimulus
lasted for more than 2 min, selective entrainment did
not occur. The frequencies in which selective
entrainment of thermoregulatory challenges occur
coincide with the very low-frequency band of the
heart rate power spectra.
Lindqvist et al. [27] have attempted to replicate
previous work by studying selective entrainment of
the power spectra using cutaneous temperature
challenges. They performed alternating rhythmic
warm and cool immersion of different skin areas at
different frequencies and water temperatures. When
102
L. A. Fleisher et al.
the frequency of the thermal stimulation was
between 0.013 and 0.096 Hz, forearm skin blood
flow oscillations synchronized to the thermal stimulation. When periodicity of heart rate was evaluated,
thermal oscillating stimulation resulted in an
increase of the low-frequency periodic HRV. In
contrast, non-specific sham stimulation significantly
modified the frequency distribution of the lowfrequency periodic HRV without changes in the
total low-frequency power compared with spontaneous conditions. The authors concluded that both
thermal stimulation and non-specific central nervous
influences induced significant and reproducible
interactions with HRV.
In contrast to the changes in very low-frequency
power seen with core cooling, the low/high ratio did
not initially change in response to thermoregulatory
vasoconstriction, but increased with the onset of
shivering. Although several investigators have suggested the usc of this ratio to indicate sympathovagal balance, others have demonstrated that the
changes in the power spectrum depend on factors
other than cardiac sympathetic nerve firings, and do
not directly relate to cardiac noradrenaline spillover
[28]. Malik and Camm [29] have suggested that
the heart rate power spectrum does not directly
measure sympathetic activity but more accurately
reflects the modulation of the autonomic nervous
system at the level of the heart. Therefore, the
changes in the low/high ratio suggest that postsynaptic sympathetic modulation of heart rate does
not occur with core hypothermia until lower body
temperatures are reached and the increased metabolic demands of shivering are induced. Vasoconstriction was associated with a decrease in heart
rate in both protocols. The response to cold challenge involves afferent input of temperature information to the hypothalamic centres, central processing of this information and an efferent response
[30]. This efferent response is characterized by
peripheral sympathetic activation as indicated by
increased noradrenaline, but no adrenal medullary
or cortical activation as determined by adrenaline
and cortisol [24, 31]. The peripheral sympathetic
activation is marked by profound vasoconstriction,
as demonstrated by an increase in the forearmfingertip temperature gradient [23]. The increase in
peripheral vascular resistance resulting from core
cooling may have been balanced by a reflex increase
in vagal tone; however, this was not supported by
the power spectral analysis. Studies in isolated rat
atrial preparations demonstrate a linear relationship
between atrial rate and temperature between 35.6°C
and 38'C [32]. This suggests that the bradycardia
observed with core cooling may have been a direct
effect of temperature on the sino-atrial node. Shivering was associated with a marked increase in heart
rate and an increase in the low/high ratio of
borderline significance. Shivering is associated with
a two- to three-fold increase in oxygen consumption
[33]. This increase in metabolic demand is met by
an increase in cardiac output; results suggest that
the increase in heart rate associated with shivering
is a result in part of an increase in sympathetic
'tone' to compensate for the increased metabolic
demand.
Skin-surface cooling results in different changes in
the heart rate power spectra than core cooling.
Sweating resulted in a decrease in HRV with an
increase in heart rate, suggesting that the increase in
heart rate is not autonomically mediated. The initial
tachycardia may be a direct thermal effect on the
sino-atrial node [32]. The difference in heart rate
power spectra between peripheral and core cooling
most probably reflects the fact that core temperatures are unchanged by peripheral cooling. However, if changes in frequency ranges of the power
spectra were compared with those during sweating,
as opposed to baseline, then power in both the very
low- and low-frequency ranges increased significantly, while heart rate decreased. This most probably reflects the profound peripheral vasoconstriction associated with this degree of skinsurface cooling. The lack of a specific response in
the very low-frequency range, as observed during
core cooling, suggests that these changes reflect a
generalized peripheral vasoconstriction, and not a
specific thermoregulatory change.
There are several limitations to the current study.
Firstly, our subjects were spontaneously breathing.
Several investigators have demonstrated that both
the respiratory rate and tidal volume can influence
the peak frequency and amplitude of the highfrequency power [34, 35]. As described in the
methods, we attempted to minimize this effect by
observing respiratory rate and determining that all
subjects breathed at greater than 12 breaths/min,
which should result in the respiratory peak being
greater than 0.125 Hz. Additionally, our primary
observations regarded the very low-frequency component, which should not be significantly affected by
these factors.
Secondly, the sampling frequency of our equipment was 120 Hz. Merli et at. [36] have suggested
that this sampling rate is the minimal acceptable
rate for calculating the power spectrum of heart
rate. In order to accurately detect the very lowfrequency component, longer data series are
required. We used a 15 min data series in the first
two protocols, which should allow us to detect
changes in the frequency band of interest.
Thirdly, our volume of cold infusion in protocol 1
may have been sufficient to change cardiopulmonary volumes and pressures. However, a similar
volume of warm saline was not shown to change
blood pressure, heart rate or H RV [31]. Therefore,
it is unlikely that the effect we observed was due to
the fluid infusion, but rather due to the change in
core temperature.
In summary, we observed a specific thermoregulatory influence on the very low-frequency component
of HRV related to core hypothermia, while skin-
Thermoregulation and R-R variability
surface temperature changes were associated with
less specific HRV changes. Further studies are
required to determine how the thermoregulatory
component modulates HRV and its importance in
relation to cardiovascular morbidity.
ACKNOWLEDGMENTS
This work was supported in part by the National
Institutes of Health GM49670, the Joseph Brown
Foundation, Mallinckrodt Medical, Inc. and
Augustine Medical, Inc. L.A.F. is supported by the
Richard S. Ross Clinician Scientist Award of the
Johns Hopkins University School of Medicine. We
acknowledge the technical expertise of Michelle
Langston for initial analysis of the electrocardiographic recordings.
REFERENCES
I. Sayers BM. Analysis of heart rate variability. Ergonomics 1973; 16: 17-32.
2. Malliani A, Pagani M. Lombardi F, Cerutti S. Cardiovascular neural regulation
explored in the frequency domain. Circulation 1991; 84: 482-92.
3. Appel ML, Berger RD. Saul IP. Smith 1M. Cohen RI. Beat to beat variability in
cardiovascular variables: noise or music! I Am Coli Cardiol 1989; 14: 1139-48.
4. Bigger IT, Fleiss IL. Steinman RC, Rolnitzky LM, Schneider WI. Stein PK.
RR variability in healthy. middle-aged persons compared with patients with
chronic heart disease or recent myocardial infarction. Circulation 1995; 91:
1936-43.
5. Bigger IT, Kleiger RE, Fleiss IL, Rolnitzky LM. Steinman RC. Miller IP.
Components of heart rate variability measured during healing of acute
myocardial infarction. Am J Cardiol 1988; 61: 208-15.
6. Kleiger RE, Miller IP, Bigger IT, Moss AI. Decreased heart rate variability and
its association with increased mortality after acute myocardial infarction. Am I
Cardiol 1987; 59: 256-62.
7. Fleisher LA. Pincus SM, Rosenbaum SH. Approximate entropy of heart rate as
a correlate of postoperative ventricular dysfunction. Anesthesiology 1993; 78:
68l-92.
8. Akselrod S. Gordon 0, Ubel FA, Shannon DC, Barger AC, Cohen RI. Power
spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat
cardiovascular control. Science (Washington DC) 1981; 213: 226-2.
9. Lombardi F. Sandrone G, Pernpruner S.et al. Heart rate variability as an
index of sympathovagal interaction after acute myocardial infarction. Am I
Cardiol 1987; 60: 1239-45.
10. Akselrod S, Gordon 0, Madwed 18, Snidman NC, Shannon DC, Cohen RI.
Hemodynamic regulation: investigation by spectral analysis. Am I Physiol 1985;
249: H867-75.
II. Kitney RI. An analysis of the thermoregulatory influences on heart rate
variability. In: Kitney RI, Rompelman I, ed. The study of heart rate variability.
Oxford: Clarendon Press, 1980: 81-106.
12. Kitney RI. The analysis and simulation of the human thermoregulatory control
system. Med 8iol Eng 1974; 12: 57-64.
13. Hyndman BW, Kitney RI. Sayers BM. Spontaneous rhythms in physiological
control systems. Nature (London) 1971; 233: 339-41.
103
14. Kitney RI, Rompelman O. The beat-by-beat investigation of cardiovascular
function: measurement. analysis. and applications. Oxford: Clarendon Press.
1987.
15. Edmonds IR. Critical tomment on the thermal entrainment of blood flow. Med
Bioi Eng Comput 1981; 5: 186-8.
16. Lindqvist A. lalonen J. Parviainen P, Antila K. Laitinen LA. Effect of posture
on spontaneous and thermally stimulated cardiovascular oscillations. Cardiovasc
Res 1990; 24: 37l-8O.
17. Cheng C. Matsukawa T, Sessler 01. et al. Increasing mean skin temperature
linearly reduces the core-temperature thresholds for vasoconstriction and
shivering in humans. Anesthesiology 1995; 82: 1I~.
18. Aguirre A, Wodicka GR. Muyan C. Shannon DC. Interaction between
respiratory and RR interval oscillations at low frequencies. I Auton Nerv Syst
1990; 29: 241-6.
19. Sessler 01. Rubinstein EH. Moayeri A. Physiologic responses to mild
perianesthetic hypothermia in humans. Anesthesiology 1991; 5: 594-610.
20. Sessler 01. Central thermoregulatory inhibition by general anesthesia
[editorial; comment]' Anesthesiology 1991; 75: S57-9.
21. Mekjavic lB. Rempel ME. Determination of esophageal probe insertion length
based on standing and sitting height. J Appl Physiol 1990; 69: 376-9.
22. Stoen R. Sessler 01. The thermoregulatory threshold is inversely proportional
to isoflurane concentration. Anesthesiology 1990; 72: 822-7.
23. Rubinstein EH. Sessler 01. Skin-surface temperature gradients correlate with
fingertip blood flow in humans. Anesthesiology 1990; 73: 541-S.
24. Frank SM, Higgins MS, Breslow MI. et al. The catecholamine. cortisol. and
hemodynamic responses to mild perioperative hypothermia: a randomized
clinical trial. Anesthesiology 1995; 82: 8l-93.
25. Berger RD. Akselrod S,Gordon D. Cohen RI. An efficient algorithm for
spectral analysis of heart rate variability. IEEE Trans Biomed Eng 1986; 33:
900-4.
26. Kitney RI, Fulton T. McDonald AH, Linkens DA. Transient interactions
between blood pressure, respiration and heart rate in man. I Biomed Eng
1985; 7: 217-24.
27. Lindqvist A, Parviainen P, lalonen J. Tuominen J. Valimaki I. Laitinen LA.
Clinical testing of thermally stimulated cardiovascular oscillations in man.
Cardiovasc Res 1991; 25: 666-75.
28. Kingwell BA, Thompson JM. Kaye OM. McPherson GA, lennings GL. Esler MD.
Heart ratespectral analysis, cardiac norepinephrine spillover. and muscle
sympathetic nerve activity during human sympathetic nervous activation and
failure. Circulation 1994; 90: 23+40.
29. Malik M. Camm AI. Components of heart rate variability-what they really
mean and what we really measure [editorial]. Am I Cardiol 1993; 72: 821-2.
30. Sessler 01. Perianesthetic thermoregulation and heat balance in humans. FA5EB
I 1993; 7: 638--+4.
31. Higgins MS. Frank SM, Breslow MI, Fleisher LA, Beattie C. The adrenergic
response to mild core hypothermia [abstractl. Anesthesiology 1994; 81: A234.
32. Bolter CP, Atkinson KI. Influence of temperature and adrenergic stimulation
on rat sinoatrial frequency. Am I Physiol 1988; 254: R84G-4.
33. Horvath GB. Spurr GB, Hutt BK. Hamilton LH. Metabolic cost ofshivering.
I Appl Physiol 1956; 8: 595-602.
H. Elghozi JL, Laude 0, Girard A. Effects of respiration on blood pressure and
heart rate variability in humans. Clin Exp Pharmacol Physiol 1991; 18: 735-42.
35. Hayano I, Mukai S. Sakakibara M. Okada A. Takata K. Fujinami T. Effects of
respiratory interval on vagal modulation of heart rate. Am J Physiol 1994; 267:
H3l-4O.
36. Merli M, Farden DC, Mottley IG. Titlebaum El. Sampling frequency of the
electrocardiogram for spectral analysis of the heart rate variability. IEEE Trans
Biomed Eng 1990; 37: 99-105.