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Vol. 84, Issue 3, 761-762, March 1998
Atelier de Physiologie Respiratoire, Faculté de Médecine Saint-Antoine, 75012 Paris, France
THE OCCURRENCE OF HYPOMETABOLISM during hypoxia was
initially described many years ago, and a recent renewed interest in
this phenomenon probably originates from the fact that the ventilatory response to hypoxia, which is now often studied in unanesthetized animals without external temperature control, may be affected by a
decrease in metabolism [oxygen uptake
( Despite many recent studies, the mechanisms responsible for hypoxic
hypometabolism remain unclear. The first possibility, proposed by
Hemingway and Birzis (9), implies an effect of hypoxia on brain
thermoregulatory mechanisms, resulting in a regulated decrease in
Tb. As such, hypoxic hypothermia,
sometimes aptly referred to as anapyrexia (2), would be the opposite of
fever. In this context, it should be noted that experimentally induced fever may be reduced by hypoxia (3). A downward resetting of the
thermoregulatory set point is suggested by studies showing that the
Ta threshold of the thermoneutral
zone, below which The second possibility that may account for hypoxic hypometabolism is a
simple limitation in oxygen availability to the tissues. There is
indirect evidence that this is unlikely because hypometabolism may
occur with mild hypoxic levels, resulting in arterial
PO2 (PaO2) values much higher
than necessary to induce a decrease in
The above results have been obtained in adult mammals, but in the
hypoxic newborn the possibility of
From the data provided, the commonly used oxygen delivery index
(cardiac output × CaO2) may be
computed during hypoxia. It then appears that
Finally, the data provided by Rohlicek et al. (11) provoke speculation
about changes in pulmonary ventilation and circulation, which are both
markedly influenced by hypoxia but differently during warm and cold
conditions.
In conclusion, this paper provides the first direct evidence that, in
newborn puppies,
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O2)] and
consequently in body temperature
(Tb) (6). Since the original
study of Hill (10), it has been recognized that several factors play an
important role in the development of hypoxic hypometabolism.
1) The size and age of the animal:
in contrast to newborn or small adult mammals or birds with a high
O2 per kilogram, the hypoxic
drop in metabolism is smaller in larger species, with a lower
O2 per kilogram (5). 2) The ambient temperature
(Ta): hypoxic hypometabolism is
greater at low ambient temperature, when
O2 is increased by
thermogenesis above values observed at thermoneutrality.
3) The level of hypoxia: a drop in
O2 may be observed with
inspired oxygen fraction
(FIO2) ranging from
0.15 to 0.17 at low Ta values,
whereas at normal Ta values, a
decrease in O2 is observed
only with FIO2 at or below
0.10. It should be noted that a drop in
O2 may also be observed with
inhalation of low concentrations of CO (7).
O2 increases, is lowered in rats exposed to hypoxia (4). Similarly, it has
been observed in cats exposed to heat that the
Ta threshold for panting is lower
in hypoxia than in normoxia (1). The hypothesis of a hypoxic lowering
in Tb set point is supported by
recent studies on behavioral thermoregulation, showing that many
organisms, including mammals, studied in a thermocline, generally
select a cooler Ta when exposed to
hypoxia (8). The increase in heat losses at lower
Ta in addition to the decrease in
O2 accentuates the hypoxic hypothermia. The way hypoxia can affect thermoregulatory centers is
unknown, but several mediators (adenosine, opioids), which are released
during hypoxia and which play also a role in
Tb regulation, are likely to be
involved in the development of hypoxic hypothermia (13).
O2 of exercising muscles (see
Ref. 6). In addition, even during sustained hypoxia,
O2 can be raised by exposure
to cold or by administration of mitochondrial uncouplers (12).
O2 being limited by the
availability of oxygen has not been positively excluded. This possibility has been explored in the study of Rohlicek et al. (11) in
this month's issue of the Journal. Conscious instrumented newborn dogs
aged 1-2 wk, studied at Ta
values of 30 or 20°C, were exposed to sequential decreases in
FIO2 from 0.21 to 0.06. O2,
CO2 production, and
Tb were measured, and arterial and
mixed venous blood samples were withdrawn through indwelling catheters,
allowing determination of several indexes of oxygen transport.
The results show that during normoxia
O2 was 70% higher at 20 than
at 30°C and that during hypoxia
O2 started to fall
significantly with a FIO2 of
0.12 at 20°C and 0.10 at 30°C. Thus, with a
FIO2 of 0.10, during both warm and cold conditions, the puppies were hypometabolic, but O2 was significantly higher
in the cold (14.1 ml · min
1 · kg1)
compared with warm conditions (11.4 ml · min1 · kg1),
despite the fact that PaO2 was slightly
lower at 20°C (25 Torr) than at 30°C (30 Torr). Similarly, at
the same mixed venous PO2 (P
O2), which may reflect the
PO2 at the tissue level, O2 was higher in
the cold than in warm conditions. This indicates that neither
PaO2 nor
was the limiting factor
accounting for the hypoxic decrease in
O2. In
addition, the linear regressions computed between
O2 and several
indexes pertinent to blood oxygenation [e.g.,
PaO2, arterial oxygen content
], have greater slopes in cold compared with warm conditions,
confirming that for a given level of oxygenation, even during hypoxic
hypometabolism O2
is higher in a cold than in a thermoneutral environment.
O2 decreases as a linear
function of oxygen delivery. This supply-dependent oxygenation
indicates, as emphasized by Rohlicek et al. (11), that these puppies do
not behave like strict "regulators," since they do not maintain
body homeostasis during hypoxia and their
Tb decreases by ~4°C.
However, the slope of the relationship between
O2 and oxygen delivery is,
like the regressions considered above, greater in cold compared with warm conditions.
O2 is
dependent on, but not limited by, oxygen supply. Therefore, it confirms
studies carried out in adult mammals, suggesting that hypometabolism is
a regulated response to an hypoxic environment.
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