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1 Second Department of Physiology, Showa University School of Medicine, Tokyo 142-8555; and 2 Department of Chest Medicine, Chiba University School of Medicine, Chiba 260-8670, Japan
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Breathing pattern is influenced by body temperature. However,
the central mechanism for changing breathing patterns is unknown. Central histamine is involved in heat loss mechanisms in behavioral studies, but little is known about its effect on breathing patterns. We
examined first the effect of body temperature on breathing patterns
with increasing hypercapnia in conscious mice and then that of the
depletion of central histamine by S(+)-
-fluoromethylhistidine hydrochloride (-FMH) (100 mg/kg ip), a specific inhibitor of histidine decarboxylase, at normal and raised body temperatures. A
raised body temperature increased respiratory frequency with reductions
in both inspiratory and expiratory time and decreased tidal volume. On
the other hand, -FMH lowered respiratory frequency with a
prolongation of expiratory time at the raised temperature; however,
this was not observed at a normal temperature. These results indicate
that central histamine contributes to an increase in respiratory
frequency as a result of a reduction in expiratory time when body
temperature is raised.
breathing pattern; carbon dioxide; -fluoromethylhistidine
hydrochloride; respiration; plethysmograph
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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RESPIRATORY OUTPUT IS REGULATED by an autonomic metabolic control system in the brain stem and by a behavioral control system in higher neural centers. Breathing pattern regulated in the brain stem is altered by input from the higher centers associated with various behaviors. There have been many studies showing that an increase in body temperature alters the breathing pattern. It is well known that panting in dogs is induced to reduce body temperature, and, even in other species that lack panting, respiratory frequency (f) is increased by a raised body temperature. The temperature effect is recognized as the effect of the higher brain on the neural networks, including respiratory centers (30), but this is still uncertain in mice. Furthermore, the mechanism underlying this temperature-induced polypnea is poorly understood.
Central histaminergic neurons have a wide distribution in the brain (10, 20) and affect thermoregulation, feeding, circadian rhythms, and various autonomic functions such as cardiovascular functions (22). Central histamine causes hypothermia in mice (2, 23) and activates the heat loss mechanisms in behavioral studies (7, 8). Considering the thermoregulatory effect and the wide distribution, central histamine may influence the respiratory system for heat loss. Recently, several studies show that central histamine decreases tracheal tension (11) and that histamine release is autoregulated by H3 receptors in the medulla oblongata in rabbits (12). As yet, however, little is known about histamine's effect on breathing pattern.
In this study, we first made a body plethysmograph for a conscious
mouse and measured respiratory variables at two different body
temperatures to clarify the effect of body temperature on breathing
pattern. Then we investigated whether central histamine affects
breathing pattern with the administration of
S(+)--fluoromethylhistidine hydrochloride (-FMH; Research
Biochemicals International, Natick, MA), which is a specific inhibitor
of histidine decarboxylase (5) and causes a marked
decrease in histidine decarboxylase activity and a concomitant decrease
in neural histamine (13). Breathing pattern was
characterized with the relationships between tidal volume (VT)
and inspiratory time (TI) and VT and
expiratory time (TE) obtained by increasing hypercapnia.
The purpose of this study was to investigate how central histamine contributes to the effect of body temperature on breathing pattern in conscious mice. Therefore, we examined 1) the effect of temperature on breathing pattern in mice and 2) whether central histamine influences breathing pattern. Finally, the relationship between the effect of temperature and central histamine on breathing pattern was discussed.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Animals. Inbred male C57BL/6N mice (8 wk old) used in this experiment were provided with food and water ad libitum, housed at a controlled temperature (22 ± 1°C), and exposed to a daily 12:12-h light-dark cycle; all experiments were conducted in an environmentally controlled room at a temperature of 22 ± 1°C.
Measurement of lung ventilation.
Ventilation was measured by double-chamber plethysmography as
illustrated in Fig. 1. We made this
system by referring to Vijayaraghavan et al. (26). A
continuous airflow through the chambers was produced by a vacuum pump
at a flow rate of 150 ml/min through a critical orifice. Airflow of the
head chamber was measured by a pneumotachograph (TV-241T and TP-602T,
Nihon Kohden) through the additional bias flow and was recorded on an
analog tape recorder (TEAC, R-71). The data stored in the tapes were
fed into analysis systems (MacLab, ADInstruments) on a Power PC
(Macintosh, Apple), at a sampling rate of 10,000 Hz. A total of 10 consecutive breaths was analyzed under each condition in a steady
state. TI (s), TE (s), total breath duration
(TT, s), and VT (ml BTPS) were
measured for each breath and averaged; f (breaths/min) was determined
as 60/TT. VT was calibrated by injecting 0.5 ml
of ambient air (22 ± 1°C) with a syringe through a small hole
of the head chamber, which was sealed during other procedures. An
elevation of the temperature of the head chamber was practically
avoided by the continuous bias flow through the experiments.
VT was calculated using the following equation
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E,
ml BTPS) was determined as f × VT.
VT and E were normalized by body weight per 10 g.
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Hypercapnic protocol. Mice were anesthetized with pentobarbital sodium (12.5 mg/kg ip) for setting in the plethysmograph. Each mouse was acclimatized to the chambers for >60 min before the assessment of ventilatory function. After the mouse recovered from anesthesia and momentary hypothermia caused by pentobarbital sodium, a bag (8 liters) was connected to the head chamber via its inlet port. Three bags contained different hypercapnic gas mixtures (5, 7, and 9% CO2 in O2). Stepwise changes in the inspired gas were produced by quickly switching to a bag containing a different gas mixture. The CO2 mixtures were applied for 4-6 min until a new steady state had been reached and were then changed to the next step. Parameters were measured at the end of each period. Rectal temperature was continuously monitored by means of a thermistor inserted into the rectum and controlled at the target temperature by a heating light from outside the chamber with an animal blanket controller (ATB-1100, Nihon Kohden).
Effects of body temperature. The experiments were performed on a total of 11 mice. Mice were loaded with hypercapnic gas mixtures according to the protocol at a body temperature of 36-37°C. After this examination, mice were allowed to rest for >3 days in preparation for the next examination. At the next examination, the body temperature was gradually raised with the controller to 39°C over a period of 30 min; subsequently, the hypercapnic protocol was run in a similar way.
Effects of -FMH.
We investigated the effect of -FMH on breathing patterns at two
different temperatures to define the role of central histamine. First,
we carried out the procedure under a normal temperature (~37°C)
using 14 mice divided into two groups of 7. -FMH was dissolved in
saline and injected at a dose of 100 mg/kg ip, and the same volume of
saline (0.2 ml) was given to the control animals. This dosage of
-FMH depletes neural histamine in mice in 4 h (13). All respiratory assessments were carried out 4 h after the injection; after a 3-h period, the mice were anesthetized and positioned in the plethysmograph, and each mouse was then placed in
the chambers for an additional 1 h and was subsequently loaded
with the hypercapnic gas mixture. To observe the effect of -FMH
under the raised temperature, we conducted the same procedure at a body
temperature of 39°C with the controller, using another group of 12 mice divided into two groups of 6.
Statistical analysis.
A commercially available software package (SPSS, SPSS Japan) was
employed. Data were analyzed with two-way ANOVA to test for effects of
CO2 and temperature or CO2 and -FMH.
Breathing pattern was statistically evaluated by the slopes and the
extrapolated VT of linear regression analysis between
VT and TI or VT and TE for each mouse. The mean slope and the VT of the
VT-TI or VT-TE line for
each condition was obtained from the average of each mouse. The
difference in the slopes between groups was examined by
t-test. Unless a difference in the slopes was detected, the difference in VT was consequently examined by the
t-test at two points, the earliest and the latest time of
overlap between the two lines. If an overlap did not exist, the
t-test was performed at the midpoint of time between two
lines. Statistical significance was accepted for
P < 0.05. Results were expressed as means ± SE.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Effects of body temperature.
Figure 2 shows the effects of body
temperature on the response of f, VT, and E
to hypercapnia. Responses to inspired CO2 on these
variables were evaluated in 11 mice at 36-37°C and at 39°C.
For all variables, there were significant effects of CO2 inhalation (all P < 0.001); CO2 produced
significant increases in f, VT, and E at
both temperatures. There was a significant increase in f
(P < 0.001) and a significant decrease in VT
(P < 0.05) at 39°C. Consequently, changes in
body temperature had no effect on E. Because there
was no significant interaction between CO2 and temperature
according to ANOVA, the responsiveness of f, VT, and
E to inspired CO2 was not changed by
temperature.
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2.007
± 0.316 ml/s at 36-37°C and
2.341 ± 0.410 ml/s at 39°C).
VT, however, significantly decreased from 0.161 ± 0.006 to 0.126 ± 0.008 ml at the same level of TI of
0.11 s at 39°C (P < 0.01). Thus the increase in
body temperature shifted the VT-TI line below
to the left. On the other hand, the slope of the
VT-TE line became steeper from
0.706 ±0.142 to 1.377 ±0.256 ml/s and
moved to the left with the body temperature raised. In summary, the
raised body temperature shifted both the VT-TI and the VT-TE lines to the left.
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Effects of -FMH.
The effects of -FMH on responses of f, VT, and
E to hypercapnia at 37°C and 39°C are shown in
Fig. 5, A and B,
respectively. CO2 significantly increased f,
VT, and E (all P < 0.001). There were no differences between the groups in f or
VT nor E at 37°C, whereas, at 39°C,
f in the -FMH-treated group was lower than in the vehicle-treated
group (P < 0.05). On the other hand, neither VT nor E was affected by -FMH.
According to ANOVA, there were no significant interactions between the
effects of CO2 and -FMH.
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-FMH on TI and TE at 37°C
and 39°C are shown in Fig.
6A, and B,
respectively. There were no differences between the groups in
TI or TE at 37°C. In contrast, -FMH
significantly prolonged TE (P < 0.05) but
had no effect on TI at 39°C. The reduction in f by
-FMH at 39°C, therefore, was caused by prolonged TE.
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-FMH-treated groups
in the relationships of VT-TI at both
temperatures. On the other hand, the slope of VT-TE was more gentle in the -FMH-treated
group (3.110 ± 0.667 ml/s) than in the vehicle-treated group
(1.421 ± 0.355 ml/s) (P < 0.05) at 39°C;
-FMH shifted the VT-TE relationship to the right. Unlike the results at 39°C, -FMH did not change
VT-TE at 37°C. In summary, breathing pattern
was influenced by -FMH at the raised body temperature but not at the
normal temperature.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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In the present study, we report a novel role for central histamine
in altering breathing pattern in conscious mice. First, we have
demonstrated that a raised body temperature caused an increase in f
with reductions in TI and TE in conscious mice. In addition, we have shown, by means of results obtained from experiments using -FMH, that central histamine contributed to temperature-induced polypnea with a reduction in TE.
Effects of body temperature.
This study showed that the raised body temperature increased f with
reductions of both TI and TE but did not change
E in conscious mice. These results were essentially
in agreement with previous studies in other species (3,
19, 27, 28). Other research has
also studied the relationship between E and either inspired, alveolar, or arterial levels of CO2. When body
temperature is raised, E response to CO2
is increased, mainly because of the augmentation in f (21,
25, 30, 31). These approaches, however, have often adopted animal models under anesthesia. Because anesthetics have an effect on the CO2 response
(6), the application of these results to the conscious
model needs careful consideration. On the other hand, in another study
using a conscious animal model, the inspired CO2 response
was elevated slightly in hyperthermia (17). However, we
were unable to measure alveolar CO2 in conscious mice
because the possibility of the animal suffering from tracheotomy prevented us from using a gas analyzer. An inconsistency between results might come partly from this experimental limitation in conscious models.
Effects of -FMH.
In this study, we examined the effect of central histamine on breathing
patterns by using -FMH. We found that central histamine contributed
to temperature-induced polypnea in mice.
-FMH-treated mice, whereas at the normal
temperature there was no difference in f between groups. These results
indicate that the effect of central histamine increased f with a
reduction in TE at a raised body temperature. The
VT-TI and the VT-TE
analyses supported this; -FMH shifted VT-TE
to the right but not VT-TI at the raised
temperature, whereas neither VT-TI nor
VT-TE was affected by -FMH at the normal temperature.
The fact that central histamine affects not TI but
TE also indicates that each parameter is able to change
independently. The control theory of rate and depth proposed by Clark
and von Euler (3), which is explained by off-switch
mechanisms located in the lower brain stem, cannot explain this
fact, because TE is therein basically dependent on
TI. To the contrary, another study suggests that there is a
separate control of TI and TE, and increases in
f are associated with reductions in TE rather than
TI in a conscious state (15); in addition, in
a conscious human study, the higher neural center is suggested to
affect predominantly f, especially TE (16).
Therefore, these results suggest that the effects of higher neural
centers, including central histamine, change TE
independently in a conscious condition.
Findings of thermoregulation by central histamine have accumulated.
Histamine immunoreactive neural fibers are distributed in the preoptic
area known as the thermoregulatory center (10, 20). Histamine, the content of which in the hypothalamus
increases at a high environmental temperature (4),
activates the warm sensitive neurons in the preoptic area
(24). Although the connection between the thermoregulatory
and the respiratory centers has not been clearly defined, central
histamine may act on breathing patterns via thermoregulatory pathways.
In general, changes in lung mechanics affect breathing patterns with
inputs from pulmonary stretch receptors. Although peripheral administrations of histamine have little effect on lung mechanics in
mice (9, 14), an administration of histamine
into the fourth ventricle increases cervical sympathetic nervous
activity and decreases tracheal tension in rabbits (11).
Changes in lung mechanics might contribute to breathing pattern changes
in our findings.
In conclusion, we have characterized the effect of central histamine on
breathing pattern. Central histamine contributed to an increase in f
caused by a raised body temperature with a reduction in TE
and formed a part of the temperature effect in conscious mice.
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FOOTNOTES |
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Address for reprint requests and other correspondence: I. Homma, Second Dept. of Physiology, Showa Univ. School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan (E-mail: ihomma{at}med.showa-u.ac.jp).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Received 2 December 1999; accepted in final form 7 April 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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1.
Bradley, GW,
von Euler C,
Marttila I,
and
Roos B.
Steady state effects of CO2 and temperature on the relationship between lung volume and inspiratory duration (Hering-Breuer threshold curve).
Acta Physiol Scand
92:
351-363,
1974[ISI][Medline].
2.
Chen, Z,
Sugimoto Y,
and
Kamei C.
Effects of intracerebroventricular injection of histamine and its related compounds on rectal temperature in mice.
Methods Find Exp Clin Pharmacol
17:
669-675,
1995[ISI][Medline].
3.
Clark, FJ,
and
von Euler C.
On the regulation of depth and rate of breathing.
J Physiol (Lond)
222:
267-295,
1972
4.
Fujimoto, K,
Sakata T,
Ookuma K,
Kurokawa M,
Yamatodani A,
and
Wada H.
Hypothalamic histamine modulates adaptive behavior of rats at high environmental temperature.
Experientia
46:
283-285,
1990[ISI][Medline].
5.
Garbarg, M,
Barbin G,
Rodergas E,
and
Schwartz JC.
Inhibition of histamine synthesis in brain by alpha-fluoromethylhistidine, a new irreversible inhibitor: in vitro and in vivo studies.
J Neurochem
35:
1045-1052,
1980[ISI][Medline].
6.
Gautier, H.
Pattern of breathing during hypoxia or hypercapnia of the awake or anesthetized cat.
Respir Physiol
27:
193-206,
1976[ISI][Medline].
7.
Green, MD,
Cox B,
and
Lomax P.
Histamine H1- and H2-receptors in the central thermoregulatory pathways of the rat.
J Neurosci Res
1:
353-359,
1975[ISI][Medline].
8.
Green, MD,
Cox B,
and
Lomax P.
Sites and mechanisms of action of histamine in the central thermoregulatory pathways of the rat.
Neuropharmacology
15:
321-324,
1976[ISI][Medline].
9.
Held, HD,
Martin C,
and
Uhlig S.
Characterization of airway and vascular responses in murine lungs.
Br J Pharmacol
126:
1191-1199,
1999[ISI][Medline].
10.
Inagaki, N,
Yamatodani A,
Ando-Yamamoto M,
Tohyama M,
Watanabe T,
and
Wada H.
Organization of histaminergic fibers in the rat brain.
J Comp Neurol
273:
283-300,
1988[ISI][Medline].
11.
Iwase, M,
Kanamaru M,
Kanamaru A,
and
Homma I.
Central histaminergic neurons regulate rabbit tracheal tension through the cervical sympathetic nerve.
J Auton Nerv Syst
74:
23-32,
1998[ISI][Medline].
12.
Kanamaru, M,
Iwase M,
and
Homma I.
Autoregulation of histamine release in medulla oblongata via H3-receptors in rabbits.
Neurosci Res
31:
53-60,
1998[ISI][Medline].
13.
Maeyama, K,
Watanabe T,
Taguchi Y,
Yamatodani A,
and
Wada H.
Effect of alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, on histamine levels in mouse tissues.
Biochem Pharmacol
31:
2367-2370,
1982[ISI][Medline].
14.
Martin, TR,
Gerard NP,
Galli SJ,
and
Drazen JM.
Pulmonary responses to bronchoconstrictor agonists in the mouse.
J Appl Physiol
64:
2318-2323,
1988
15.
Martin-Body, RL,
and
Sinclair JD.
Analysis of respiratory patterns in the awake and in the halothane anaesthetised rat.
Respir Physiol
61:
105-113,
1985[ISI][Medline].
16.
Masaoka, Y,
and
Homma I.
Expiratory time determined by individual anxiety levels in humans.
J Appl Physiol
86:
1329-1336,
1999
17.
Maskrey, M.
Body temperature effects on hypoxic and hypercapnic responses in awake rats.
Am J Physiol Regulatory Integrative Comp Physiol
259:
R492-R498,
1990
18.
Mortola, JP,
and
Gautier H.
Interaction between metabolism and ventilation: effects of respiratory gases and temperature.
In: Regulation of Breathing (2nd ed.), edited by Dempsey JA,
and Pack AI.. New York: Dekker, 1995, p. 1011-1064.
19.
Olievier, CN,
Berkenbosch A,
and
DeGoede J.
Effect of temperature on the ventilatory response curve to carbon dioxide in anaesthetized cats.
Respir Physiol
47:
365-377,
1982[ISI][Medline].
20.
Panula, P,
Pirvola U,
Auvinen S,
and
Airaksinen MS.
Histamine-immunoreactive nerve fibers in the rat brain.
Neuroscience
28:
585-610,
1989[ISI][Medline].
21.
Petersen, ES,
and
Vejby-Christensen H.
Effects of body temperature on ventilatory response to hypoxia and breathing pattern in man.
J Appl Physiol
42:
492-500,
1977
22.
Schwartz, JC,
Arrang JM,
Garbarg M,
Pollard H,
and
Ruat M.
Histaminergic transmission in the mammalian brain.
Physiol Rev
71:
1-51,
1991
23.
Shaw, GG.
Hypothermia produced in mice by histamine acting on the central nervous system.
Br J Pharmacol
42:
205-214,
1971[ISI][Medline].
24.
Tsai, CL,
Matsumura K,
Nakayama T,
Itowi N,
Yamatodani A,
and
Wada H.
Effects of histamine on thermosensitive neurons in rat preoptic slice preparations.
Neurosci Lett
102:
297-302,
1989[ISI][Medline].
25.
Vejby-Christensen, H,
and
Petersen ES.
Effect of body temperature and hypoxia on the ventilatory CO2 response in man.
Respir Physiol
19:
322-332,
1973[ISI][Medline].
26.
Vijayaraghavan, R,
Schaper M,
Thompson R,
Stock M,
and
Alarie Y.
Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract.
Arch Toxicol
67:
478-490,
1993[ISI][Medline].
27.
Von Euler, C,
Marttila I,
Remmers JE,
and
Trippenbach T.
Effects of lesions in the parabrachial nucleus on the mechanisms for central and reflex termination of inspiration in the cat.
Acta Physiol Scand
96:
324-337,
1976[ISI][Medline].
28.
Von Euler, C,
and
Trippenbach T.
Temperature effects on the inflation reflex during expiratory time in the cat.
Acta Physiol Scand
96:
338-350,
1976[ISI][Medline].
29.
Von Euler, C,
and
Trippenbach T.
Excitability changes of the inspiratory "off-switch" mechanism tested by electrical stimulation in nucleus parabrachialis in the cat.
Acta Physiol Scand
97:
175-188,
1976[ISI][Medline].
30.
Von Euler, C,
Wexler I,
and
Herrero F.
Control mechanisms determining rate and depth of respiratory movements.
Respir Physiol
10:
93-108,
1970[ISI][Medline].
31.
Widdicombe, JG,
and
Winning A.
Effects of hypoxia, hypercapnia and changes in body temperature on the pattern of breathing in cats.
Respir Physiol
21:
203-221,
1974[ISI][Medline].
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) and
at 39°C (
), tidal volume (VT,
middle), and minute ventilation (bottom).
Significant main effect for inspired CO2
(*** P < 0.001); significant main effect for
temperature (
P < 0.05, 
