Biology Reference
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The parameters directly provided by plethysmography are respi-
ratory frequency (fR) and tidal volume ( V T ), while ventilation
must be calculated by multiplying fR with V T . Plethysmography is
technically demanding and requires a relatively complex set-up to
accurately generate the desired air regimen and adequately
acquire, register, and analyze data. Accordingly, the influence of
several parameters, such as O 2 exposure regimen, air flow, ambi-
ent temperature within the chamber, evaporating water, and ani-
mal body temperature, must be taken into account.
Plethysmography is an invaluable technique in respiratory physi-
ology since it allows determination of the ventilatory parameters
of an animal kept under physiological conditions (unanesthetized
and unrestrained) during a relatively long period of time and
inside a controlled environment. Once again, the concept under-
lying the barometric plethysmography system is to measure, in a
hermetically closed chamber, the fluctuation of pressure produced
by the respiration of the animal.
In our laboratory, plethysmography was a key method to
determine that erythropoietin (Epo), is implicated in the modu-
lation of the neural control system both at central (brainstem)
as peripheral (carotid bodies) levels. We specifically demon-
strated that Epo in adult mice improves the acute hypoxic ven-
tilatory response, as well as the ventilatory acclimatization to
hypoxia ( 2 ). Indeed, we have shown for the first time that neu-
ral respiratory and erythropoietic systems are tightly intercon-
nected, thus playing a complementary role improving the tissue
oxygenation upon hypoxia ( 2, 12 ). Moreover, we have further
expanded these findings showing that chronic hypoxic exposure
produces a drastic down-regulation of the soluble Epo receptor
(sEpoR—a truncated form of the Epo receptor, that binds and
inactivates endogenous Epo) in the central nervous system in
mice. Furthermore, when sEpoR was chronically infused in the
mouse's central nervous system, the process of ventilatory accli-
matization to chronic hypoxia was abolished. These results
showed that neural regulation of Epo and its antagonist sEpoR
play a contra-balancing role in the central nervous system in
establishing ventilatory activity and ensuring systemic oxygen
delivery under low O 2 conditions ( 1 ). Finally, still by using
plethysmography, we demonstrated that the impact of Epo on
ventilation occurs in a sex-dependent manner. Keeping in mind
that women are less susceptible to several respiratory diseases
than men, these findings suggest that Epo plays a key role in
sexually dimorphic hypoxic ventilation ( 1 ). All together, these
results foresee that Epo has a potential therapeutic use as treat-
ment for hypoxia-associated ventilatory diseases. This review
describes how to measure basal ventilation and hypoxia ventila-
tory response in adult mice (see Note 1) under unrestrained
conditions (see Note 2).
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