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Eur Respir J
1990, 3, 414-420
Circadian rhythms of specific airway conductance
and bronchial reactivity to histamine:
the effects of parasympathetic blockade
D. Dreher, E.A. Koller
Circadian rhythms of specific airway conductance and bronchial reactivity to
histamine: the effects of parasympathetic blockade. D. Dreher, EA. Koller.
ABSTRACT: In ten healthy, nonsmoking, non-atopic, young volunteers,
specific nlrwuy conductance and bronchial response to aerosolized histamine were meas ured plethysmographkally at intervals of 4.8 h during two
pel'lods of 24 h, i.e. one day without, the other with, a parllSympatholytlc
aerosol (0.20-0.24 mg ipratroplum bromide) Inhaled 1 h before each
mensurement, In order to determine the role of the parasympathetlc Innervation In the circadian rhyth ms of the airways. SpecLrlc airway conductance and bronchial reactivity showed clear circadian variations with
con·espondln g peak limes (16.11 and 04.4 1 h, respectively). Topical vagal
blockade markedly Increased speclrlc conductance and resulted In a
significant reduction of Its rhyth m amplitude, whereby tlte strong correla·
tlon between speclrlc conductance and heart r ate was significantly
di mlnJshed. On the other hand, bronchial reactivity to histamine was
lowered without Oattenlng of Its circadian rhythm. Tt Is concluded that
central parasympathetlc outnow Is no essential factor for the circadian
rhythm of bronchial tone and, thus, for the Increase In bronchial resistance
at night.
Eur Respir J., 1990, 3, 414--420.
The importance of chronobiology for diagnosis and
trcauncnt of reversible airways obstruction has been increasingly recognized in recent years [1, 2]. Various
studies have shown circadian changes in airway calibre
in healthy [3-5) and in asthmatic subjectS [6-8]. Moreover, day/night variations of bronchial reactivity have
been demonstrated for unspecific [9-1 1] and for antigenic (12] irritantS. However, the mechanisms underlying the circadian variations of airway resistance, and
the mechanisms mediating the rhythm in bronchial reactivity, are not yet clear. Our aim was to illuminate the
role of the autonomous nervous system (in this paper the
impact of the parasympathetic lung innervation) with
appropriate plethysmographic and statistical methods in
heaJlhy subjectS.
Bronchomotor tone, i.e. the parasympathetic outflow
to the bronchial muscles and glands, resultS, in the healthy
as well as in the asthmatic subject, from central vagal
tone and the afferent vagal input arising from the pulmonary reccptors [13]. Thus, these vagal receptors initiate,
among other effectS, the reflex changes in airway calibre
due to inspiration and expiration during normal breathing as well as the rel1ex changes due to increased bronchial reactivity produced by asthmogenic substances [14].
On the other hand, the parasympathetic system is
Dept of Physiology, University of Zurich,
Winterthurerstrasse 190, CH-8057 Zu rich,
Switzerland.
Correspondence: Dept of Physiology, University of
Zurich, Winter1hurerstrasse 190, CH-8057 Zurich,
Switzerland.
Keywords: Airway calibre; body plethysmography;
bronchial provocation test; bronchial reactivity;
circadian thythm; heart rate; histamine; ipratropium
bromide.
Received: August, 1988; accepted after revision
August 9, 1989.
This study was supported in pan by "Stiftung fur
wissenschaftliche Forschung an der Universitiit
Zurich" and by '"lbeodor und lda Herz.og-Eg1iStiftung, Zurich."
supposed to play an important role in controlling the
day/night variations of both airway calibre and bronchial reactivity. Only two studies have investigated the
influence of parasympathetic blockade on the circadian
rhythm of airway calibre by measuring bronchial resistance [3, 4]. Their findings were opposed; however, neither paper provided direct statistical comparison between
the rhythms before and after the parasympatholytic treatment. The role of vagal tone in the nocturnal increase of
bronchial reactivity is, to our knowledge, investigated
for the first time in this study.
Our experimentS were designed to show the role of
the parasympathetic lung innervation in both airway
calibre and bronchial reactivity in selected heal!hy
subjects, using ipratropium bromide inhaled in high
dosage to achieve the topical blockade of the pulmonary
parasympathctic innervation_ In order to avoid external
influences on the endogenous rhythms, the following
principles were adhered to: 1) body plethysmography
ensured measures independent from the subjects
compliance; 2) the chronological design of the study was
adjusted to the i nd i vi d uaJ activity pattern; 3) the
subjects were kept free from agentS (drugs, nicotine,
caffeine, etc.) which might affect lung functions or heart
rate.
CIRCADIAN RHYTHMS OF BRONCHOMOTOR TONE
Methods
Subjects
Ten heallhy young medical students (7 males and 3
females) gave their informed consent to the experiments.
The subjects were 21-29 yrs old, nonsmokers, with no
history of allergic diseases and with normal
cardiopulmonary functions. Their physical characteristics and sleeping habits are recorded in table 1. Before
and during the trials, no medication was allowed;
food-intake and physical activity followed the
Guidelines of the Assembly of Allergy and Clinical
Immunology, A.T.S. [15).
Table 1. - Anthropometric and lung function data,
mid-sleep (n=10)
Mean
Age yrs
Height m
VC I
FEV1 %VC
TGV I
sGaw mb·sec·'
PD 3s mg
Mid-sleep h·min· 1
23
1.76
5.11
78
3.5
0.27
0.22
3.43
Minimum
value
Maximum
value
21
1.65
3.70
67
2.5
0.19
0.03
2.00
29
1.83
6.24
93
4.4
0.38
0.53
6.00
VC: vital capacity; FEV1: forced expiratory volume in one
second; TGV: total gas volume; sGaw: specific airway conducLance; PD35: provocative dose producing 35% fall in sGaw.
Study design
In this transversely designed study, interindividual differences in the timing of the circadian system were
adjusted by setting the middle of the habitual sleep span
("mid-sleep", MS) as reference for the chronological
design of the study. 2 x 5 equidistant blocks of measurements during two periods of 24 h were grouped around
mid-sleep, i.e. at: 1) MS -9.6 h; 2) MS -4.8 h; 3) MS; 4)
MS +4.8 h; 5) MS +9.6 h. The subjects were asked to
stay in bed between the last measurement block (MB)
before mid-sleep (MS) and the first MB after MS, except
for one interruption for the MB at MS (comparable disruption of sleep in asthmatic subjects was without apparent effect on lung functions [16]), thus resulting in at
least 7 h of rest. However, the findings are presented in
relation to midnight (midnight= MS -3.72 h). Every MB
included consecutive determination of resting heart rate,
specific airway conductance (sGaw) and bronchial reactivity to hislamine (bRH).
Each of the ten volunteers underwent two experimental periods of 24 h: five subjects were measured without
drug on the first day (control period) and with ipratropium on the following day (drug period), whilst the five
other subjects began wilh the drug period and continued
with the control period on the third day. During the drug
period, ipratropium bromide from a metered-dose aerosolizer (Atroveml!>) was inhaled during slow maximal
415
inspirations, starting from functional residual capacity.
In order to achieve an effective dose of 0.24 mg [17]
with a maximum drug effect during the MB, twelve puffs
of ipratropium (0.02 mg per puff) were given 1 h before
the first MB [18], and ten puffs 1 h before each of the
following MBs. A placebo series or double-blind study
was excluded, since the volunteers, all medical students,
easily distinguished the characteristic taste of ipratropium
from that of available placebos. Systematic placebo
effects, however, would not affect the cosinor analysis
which compares repeated measurements within the same
treatment period (see below).
Measurements
Heart rate was detennined from the subjects electrocardiogram (ECG) during 1 min after 20 min at rest in
the supine position. In this time the subject was allowed
to close his eyes but was asked to stay awake.
Measurements of airway resistance (Raw) and thoracic
gas volume (TGV) were performed in a constant volume
body plethysmograph with on-line data processing
(Bodystar FG 90. Or Fenyves & Gut). Our modifications
of the box included complete lining of the air-conduit
system with thermoregulated aluminium tubes in order
to avoid deviations from body temperature and standard
atmospheric pressure saturated with water vapour {BTPs)
conditions, thus essentially improving the reliability and
reproducibility of the measurements. Before each measurement block (MB), the equipment was calibrated by a
specifically designed electric piston pump [19]. Detennination of sGaw and bronchial reactivity was based on
triplets of plethysmographic measurements. Each triplet
included three cycles of tidal breathing, each evaluated
at 4 points at ±1 /-s·1 , and was followed by estimation of
TGV with closed mouth-shutter. sGaw of one triplet was
calculated as the reciprocal of mean Raw of the nearest
two measurements multiplied by TGV, thus compensating for intra-individual changes in lung volume [20]. In
the present study, the mean standard deviation of sGaw,
detennined from one triplet, was <7%. sGaw of an MB
was obtained from five triplets successively measured
within 10 min. 1,500 plethysmographic measurements
were thus performed in this study for detenninations of
sGaw, whilst about 3,000 breathing cycles were evaluated for calculations of bronchial reactivity (see below).
Bronchial provocation tests were perfonned with different doses of histamine solutions prepared according to
the standard of the Asthma and Allergic Disease Centers,
USA [21]. Within the week preceding the measurement
period, the individual threshold dose of histamine causing a 35% fall in sGaw (PD 35) was estimated by an
interpolation method [22]: firstly, this detennination
enabled preliminary exclusion of hyperreactive subjects;
secondly, PD 5 served as provocation dose for the
bronchial inh;ration test. Instead of repeating the interpolation procedure in the MB, bronchial reactivity was
determined as the airway response to the predetennined
PD3 (see below). This method, fully described by GERvAis
et a?. [12]. yields higher reproducibility with direct results
D. DREHER, E. A. KOLLER
416
(i.e. without interpolation) and avoids inconstant,
cumulative effects of the agent. The bronchial provocation test was carried out outside the body plethysmograph under screen control of respiratory volume and
frequency. A French-Rosenthal Dosimeter (John Hopkins
School of Medicine, Baltimore) was triggered on
inspiration to deliver air during 0.6 s at 0.4 bar to the
DeVilbiss No. 646-Nebulizer. After inhalation, triplets
of plethysmographic measurements were recorded every
1 or 2 min, until sGaw recovered by increasing values,
but at least during 6 min. Bronchial reactivity was
defined as the percentage decrease between the lowest
sGaw in the MB after inhalation of ten puffs of an
isotonic NaCl solution and the lowest sGaw after the
ensuing PD35 inhalation, also distributed on ten successive puffs. With an interval of 4.8 h between the
histamine inhalation tests neither cumulative nor tachyphylactic effects should be expected [23].
of the parasympatholytic agent (mean r = 0.32, p<O.OS)
shows that the association between both parameters is
significantly reduced in the treatment group (p<O.OS). In
figure 3, the variations from all subjects as compared to
the individual period means are depicted, illustrating the
loss of association between sGaw and heart rate as the
parasympathetic innervation of the airways is blocked.
sGaw
Reactivity
0.5
0.4
:::;....
0.3
Ill
.i:a
§.o.2
H+t-H
~~
r
0.1
0
I
0 .0 '\-----12.00
Statistical analyses
Linear regression analysis was used for determination
of correlation coefficients. Day/night variations of sGaw
and bronchial reactivity to histamine were quantified by
the cosinor analysis introduced by RALBERG et al. [24],
who used multiple regression analysis to fit cosinusoidal
curves to individual time series data, assuming a 24 h
periodicity for circadian rhythms. A rhythm was found
to be significant if the amplitude of the curve differed
from zero with p<O.OS. Differences between the single
rhythm amplitudes and between the single correlation
coefficients of the control and the drug period were
evaluated by Fisher's paired t-test. Parameters of group
rhythms with and without treatment were estimated by
group mean cosinor analysis according to NELSON et al.
[25]. Within group cosinor analysis, significance of
rhythm detection and differences between group rhythms
were assessed by the zero-amplitude and the amplitudeacrophase test, respectively. For all time series modelling, SAS/ETS"' software, together with base SAS®
software, was used (SAS Institute Inc.).
c
0
60
50
n
t
40
it
i
0
s:
•
20 il
I
30
~f
:E
10
---.----+---- --.--- --/ 0.0
00.00
12.00
nme
00.00
12.00
h
Fig. 1.- Variations of sGaw and bRH with and without parasympathetic blockade: mean values±sBM. Time related to midnight (00.00)
(n=lO). sGaw: specific airway conductance; bRH: bronchial reactivity
to histamine.
0.7
0 .07
0.6
0.06
0.05
•;>
lE
0.04i
0.03~
0.02
0 .2
0.01
0 . 1 -...,.-------y-''-y-------~ 0.00
Drug Control
Control
Drug
Fig. 2. - sGaw: effect of parasympathetic blockade on individual
period means and individual rhythm amplitudes (n=lO). sGaw: specific
airway conductance.
Results
Control
Drug
Specific airway conductance
The chronogram of sGaw is presented in figure 1. The
diagram shows maximum sGaw values at 13.19 h in the
second measurement block after mid-sleep (MS +9.6 h);
this peak time is not changed by the parasympathetic
blockade. The drug, however, shifts mean sGaw from
0.22 to 0.39 (mb·s)· 1 , i.e. by 80%, as in all subjects the
parasympatholytic treatment resulted in a marked bronchodilatation (fig. 2). For each subject, coefficients of
correlation were calculated between the deviations of
sGaw and heart rate from the period mean. In the control
group, the mean coefficent of correlation amounts to 0.78
and is significantly different from zero (p<0.001). Pairwise
comparison to the individual coefficients after inhalation
-10
0
+10
+20
-20
-10
u
+10
·20
Heart rate beats·mln·1
Heart rate beats·mln·1
Fig. 3. - Relationhips between sGaw and heart rate with and without
blockade of the parasympathetic lung innervation: deviations from
period mean and linear regression analysis with 95% confidence limits
(n=50). sGaw: specific airway conductance.
417
CIRCAIDIAN RHYTHMS OF BRONCHOMOTOR TONE
Cosinor analysis was performed on individual data as
well as on group data. The individual rhythm amplitudes
(half the difference between maximum and minimum)
during the control and the drug period are displayed in
figure 2. Paired t-test comparison of the individual rhythm
amplitudes of sGaw with and without drug reveals a
significant reduction of single amplitudes by the parasympathetic blockade (p<0.05). This reduction, however,
is not correlated to the individual increase in mean sGaw
(r = -0.12, p>O.l).
The results of group mean cosinor analysis are listed
in table 2, and the group rhythms with and without treatment are depicted in figure 4. During the control period,
sGaw describes a distinct rhythm with the acrophase (time
of maximum) occurring at 16.11 h (MS +12.3 h). After
parasympathetic blockade, circadian variations of sGaw
are still detectable (p<0.05), the drug, however, results in
a reduction of the group rhythm amplitude from 16 to
4% of the mesor (mean level). Group cosinor analysis
verifies a significant difference between the group rhythms
with and without parasympatholytic blockade (table 2).
sGaw
Reactivity
50
0.4 5
40
'#
0.35
30 ~
3"
20
Ill
C)
Ill
~
10
0.0
12.00
0 . 15 ~----~~-----+------~------~
12.00
00.00
12.00
00.00
Tlme h
Fig. 4. - Circadian rhylhms of sGaw and bRll wilh and without
parasympathctic blockade: group mean wilh 95% confidence limits of
amplitude. Time related to midnight (00.00) (n= lO). sGaw: specific
airway concuctance; bRH: bronchial reactivity to histamine.
Table 2. - Results of group cosinor analysis (n• 10)
sGaw mb·s·1
bRH% sGaw
Period
F(p)
Mesor
control
drug
control
drug
26.37***
5.04*
22.0***
13.10***
0.22
0.39
37.2
9.9
Amplitude Acrophase h·min·1
±95% confidence interval
0.03±0.01
0.01±0.01
6.7±2.2
5.1±2.6
16.1±01.3
14.2±03.5
04.4±01.3
04.4±02.0
F values obtained from cosinor analysis. One-tailed pvalues given for the hypothesis
of rhylhm-amplitude = 0; *: p<0.05, ***: p<O.OOl. Acrophases related 10 midnight
(= mid-sleep-related acrophascs +3.4 h).sGaw: specific airway conductance; bRH:
bronchial reactivity to histamine.
Bronchial reactivity to histamine
During both the control and the drug period, highest
bronchial reactivity to histamine is found in the MB at
03.4 h, corresponding to MS (fig. 1). The parasympatholytic drug essentially reduces bronchial reactivity:
the minimum individual decrease amounts to 42%, the
maximum individual reduction to 85%. The group
mean reactivity to the PD35 is reduced by 73%, i.e., from
37.2% during the control period to 9.9% during parasympathe tic blockade.
Group cosinor analysis of the reactivity measurements
without tre atme nt reveals a significant circadian
periodicity: the acrophase of the group rhythm is found
at 04.41 h (MS +0.58 h), the rhythm amplitude is 8%
of the mesor (mean level). Correspondingly, during the
drug period a clear circadian group rhythm is found
with a very similar peak time at 04.42 (MS +0.59 h),
whilst the rhythm amplitude of the reactivity is slightly
lowered to 6% of the mesor (table 2 and fig. 4).
Comparison of the rhythms with and without drug by
the amplitude-acrophase test shows no significant difference between the control and drug periods (table 2).
Discussion
This study was designed to determine the role of vagal
motor innervation of the airways in mediating the circadian variations of both airway calibre and bronchial
reactivity to histamine in healthy subjects. The choice of
body plethysmography for evaluation of changes in airway dimensions based on the experience that other test
methods, such as forced expiratory volume in one
second (FEV1) and peak expiratory flow rate (PEFR)
depend on the subjects compliance [20]. The latter, however, would probably also show circadian variations. In
addition, these tests require initial deep inspirations to
total lung capacity and thus alter baseline airway tone
and bronchial reactivity to bronchoconstrictor agents [26] .
Therefore, in contrast to other authors who used forced
expiratory manoeuvres to monitor the airway responses
[9-12], we avoided maximum respiratory manoeuvres
during the bronchial provocation test also. Circadian
rhythms of sGaw and bronchial reactivity were verified
by the cosinor analysis, a standard method of chronobiology, which has proved to be appropriate for the evaluation of circadian periodicity in lung functions
418
D. DREHER,
[2, 4, 8, 10-12]. According to REINBERG and GERVAIS
[8], for measurements of circadian rhythms in the
airways "five times a day would be a good index and we
need at least six days of study for longitudinal study or
six subjects for one day for a transverse srudy". In our
experiments, a transverse design with ten subjects was
chosen in order to reduce the volunteers individual strain
and to promote general validity of the results.
Agreement in the chronophysiological pattern of airway resistance was found between our plethysmographic
studies and those of others. Under carefully controlled
conditions, KERR [5] found sGaw of six normal subjects
to be lowest at 04.00 h with amplitudes of20% (study 1)
and 14% (study 2) of the mesor (mean level). GAULTIER
et al. [4], in two groups of healthy children, detected
acrophases of specific airway resistance (sRaw) at 05.39
h and 03.31 h, respectively; results which correspond
well to our findings in healthy students with 04.11 h for
the minimum of sGaw. The relative rhythm amplitudes
in their groups amounted to 11 and 15%, respectively,
whilst the group rhythm amplitude in our study was 16%
of the mesor.
Circadian variations of bronchial reactivity have also
been demonstrated in several non-plethysmographic studies (see above). DE VRIEs et al. [9] found that sensitivity
to inhaled histamine in eleven patients with bronchial
asthma was markedly increased at night, whilst a more
recent investigation, on seven asthmatic subjects, demonstrated individual circadian rhythms of airway responsiveness to histamine varying in acrophases, i.e. times of
highest reactivity, from 21.8 h to 11.1 h [10]. REINBERG
et al. [11], in a group of eight normal subjects, showed
that bronchial sensitivity to acetylcholine had a rhythm
amplitude amounting to 30% of the mesor with the
acrophase occurring at 02.54 h. We also found a distinct
circadian rhythm of bronchial reactivity to histamine in
normal subjects, with an amplitude of 22% of the mesor
and the peak time at 04.41 h. These findings indicate that
bronchial responsiveness shows day/night variations
which are not restricted to asthmatic subjects or to a
specific bronchoconstrictor agent.
Blockade of the parasympathetic lung innervation produced different effects on the circadian rhythms of sGaw
and bronchial reac tivity to hjstamine: rugh doses of
inhaled ipratropium bromide (0.24 mg) markedly lessened bronchial muscle tone and the rhythm in airway
calibre, on the olher hand bronchial reactivity to histamine was lowered wiLhout s ignificant flattening of its
circadian rhythm. De Mill.As and ULMER [3] were the
ftrSLLo study the influence of the vagolytic agent ipratropium bromide io a rather low dosage (0.025 mg) on the
day/night patte rn of airway res is tance in healthy
subjects; they found with ipratropium circadian variations
of Raw running unchanged but on a lower level; the
comparison of the rhythms with and without drug,
however, was not based on the cosinor method. GAULTIER
et al. [4] described, in healthy children, a circadian rhythm
in sRaw after 0.08 mg of ipratropium bromide, but with
a dosage of 0.20 mg the rhythm in airway resistance was
no longer detectable. Although based on only three
s ubjects and not showing a significant difference
E.A.
KOLLER
between pre- and post-treatment rhythms by the amplitude-acrophase test, the authors assumed that the anticholinergic drug had suppressed the circadian rhythm,
while lower dosages did not reduce the nocturnal
increase in sRaw owing to insufficient blockade of parasympathetic activity at night, when vagal tone is highest.
Our present study in healthy subjects supports the
conclusion that ipratropium bromide inhaled in high
dosage effectively reduces the circadian rhythm of
airway resistance.
Nocturnal airway narrowing has been most consistently
proposed to be due to increased vagal tone, decreased
plasma adrenaline, and/or a fall in plasma corticosteroids
[1). In contrast to the effects of the vagolytic agent in our
study, overnight treatment with 132 -agonists [27] or
cortisol infusion [28] led to bronchodilation without
reducing the circadian change of airway calibre.
Systemic 13-adrenergic blockade with high doses of
propranolol (160 mg initial dosage+ 80 mg before each
measurement block) had no effect on the circadian rhythm
of airway resistance or on bronchial sensitivity to histamine in our recent, similary designed follow-up study
[10]. These findings suggest that vagal bronchomotor tone
is the essential part of the autonomous nervous system in
mediating the circadian rhythm of airway calibre.
The circadian variations of sGaw are strongly correlated with those of resting heart rate; at night both
parameters reflect increased parasympathetic activity [30).
In our experiments the parasympatholytic aerosol inhaled
in high doses led to blockade of the vagal bronchomotor
fibres and thus to bronchodilatation, but did not affect
the parasympathetic innervation of the heart. Therefore,
we may conclude that the ipratropium aerosol topically
blocks the parasympathetic lung innervation. The clinical and therapeutic impact of this conclusion is obvious
in nocturnal bronchial asthma: in a recent clinical study,
nocturnal airway obstruction was significantly reduced
by high doses of an inhaled anticholinergic agent (7].
Parasympathetic blockade significantly lowered bronchial reactivity to histamine by reducing bronchial muscle
tone, but the circadian rhythm of bronchial reactivity was
not reduced. The persistance of the reactivity rhythm
under parasympathetic blockade suggests that the higher
vagal activity at night does not cause the nocturnal
increase in airway responsiveness to histamine, which
therefore depends on other nervous and/or humoral
factors. Since in normal subjects our method of bronchoprovocative testing predominantly reflects reactivity
of the larger airways [20] , these findings might be
different in asthmatic pa tients.
As bronchomotor tone, apart from the influence of the
central oscillator, underlies reflex mechanisms in both
the normal and the asthmatic subject, it should be pointed
out that bronchial reactivity may affect, by vago-vagally
mediated reflexes, the bronchial resistance [13, 14]. Corresponding acrophases of bronchial reactivity and airway
resistance would support this assumption. We therefore
conclude that the circadian rhythm in bronchial reactivity superimposes on the rhythm of airway resistance, thus
probably contributing to the aggravation of symptoms of
nocturnal asthma in hyperreactive patients. Further, the
419
CIRCADIAN RHYTHMS OF BRONCHOMOTOR TONE
nocturnal increase of bronchial reactivity is of lessened
clinical impact if bronchomotor activity and vagally
mediated reflex bronchoconstriction are blocked by high
doses of a topical parasympatholytic agent
Conclusions
In healthy, non-atopic, nonsmoking subjects high doses
of inhaled ipratropium bromide lead to marked bronchodilatation but do not affect the parasympathetic
innervation of the heart. The topically acting parasympatholytic aerosol in high dosage causes a significant
flattening of the circadian rhythm in airway calibre and,
per analogiam, probably of the excessive rhythm amplitude in nocturnal asthma. In healthy subjects bronchial
reactivity to histamine is essentially reduced by the
blockade of the parasympathetic lung innervation; its
persistent circadian rhythm, however, underlies other
nervous and/or humoral factors.
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Rythmes circadiens de la conductance specijique abienne et
de la reaclivite bronchique /'histamine: effets du blocage
vagal. D. Dreher. EA. Koller.
RESUME: La conductance specifique et la reponse des voies
aenennes a!'histamine, appliquee par a6rosol, ont ete mesurees,
dans un groupe de 10 sujets sains, jeunes, non-fumeurs et non
atopiques, par plethysmographic corporelle dans des intervalles
de 4.8 h durant deux periodes de 24 h, i.e. un jo\D' sans, 1' autre
avec un aerosol parasympatholytique (0.20-0.24 mg bromure
d'ipratropium) inhale 1 h avant chaque mesure dans le but de
a
420
D. DREHER, E.A. KOLLER
determiner le role de !'innervation parasympathique dans les
rythmes circadiens des voies aeriennes. La conductance
specifique et la reactivite bronchlque ont montre clairement des
variations circadiennes avec les acrophases analogues (16.11 h
et 04.41 h, rcspectivement). Le blocage vagal des voies aeriennes a augmente sensiblement la conductance specifique et a
provoque une reduction sign.ificative de I' amplitude de son
rythme; en outre la correlation significative entre la
conductance specifique et la frequence cardiaque a ere eliminee
par l'aerosol parasympatholytique. D'autre part, la reactivite
bronchique a !'histamine a ete abaissee sans attenuation
sign.ificative du rythme circadien. De ces resultats, il est conclu
que !'efflux central parasympathique est un facteur essentiel
dans le rytlune circadien du tonus bronchique et par consequent
dans ]'augmentation nocturne de la resistance bronchique.
Eur Respir J., 1990, 3, 414-420.