Introduction
Hypothermia achieved by physical and/or pharmacological cooling is
widely used in medicine at cardiac arrest, ischemic or traumatic injury
of different organs . In addition, the state of pharmacological
hibernation or synthetic torpor, accompanied by a decrease in body
temperature and by suppression of metabolic activity, is supposed to be
used for long-term space travel .
Most mammals, known as homeotherms, are able to maintain a constant body
temperature throughout their lives. However, during the winter cold
period, which is characteristic of high latitudes, or the lack of water
and food in the desert, some mammals, called heterotherms, have acquired
the ability to adapt by reducing the body temperature. Analysis of the
metabolism of heterotherms allowed dividing them into two large groups:
daily heterotherms, who are able to be in a state of torpor for hours,
and true hibernations, capable of being in a state of torpor for many
days and even months . Due to reduced metabolic rate, hibernating
animals have increased resistance to adverse environmental factors,
including low temperatures, lack of food and water, and long-term
mobility restriction .
Studies of the dependence of metabolic rate on temperature are an
important part of theoretical biology, namely metabolic theory of
ecology (MTE). It has been further developed by West, Brown, and Enquist
and known at present as WBE-theory and now tested on a wide variety of
plants and animals from unicellular to higher organisms . According to
the principles of allometric scaling proposed by WBE-theory, the
metabolic rate depends on two variables: body mass and body temperature
according to equation :
I = io M 3/4e-E/kT (1)
Symbols used: M – body mass, E – activation energy of
metabolism, Eс - corrected activation energy of
metabolism, k – Boltzmann constant, T – body temperature
in Kelvin degrees.
Note: the body mass (M ) is taken with exponent 3/4 in accordance
with Kleiber’s law and used in the model of allometric scaling of body
sizes .
For the convenience of analysis, it was suggested to use the logarithmic
expression of the above formula:
ln(I/M3/4) = – E(1/kT) +
ln(io) (2)
This expression is a linear equation. The slope coefficient of this
straight line (E ) corresponds to the metabolic activation energy,
which is assumed to be in the range of -0.6 eV – -0.7 eV for all
organisms from unicellular to giant mammals and plants . The
mathematical expression ln(IM3/4) , sometimes
called the mass corrected metabolic rate, reflects the energy released
by the body during aerobic respiration, which in mammals significantly
exceeds the heat output from anaerobic processes. Therefore, we can
consider this expression as an assessment of the body’s internal heat
production. When analyzing the temperature dependence of E for
homeothermic animals, with the fact that body temperature of these
animals is normally kept constant, appropriate measurements of Ein most species of mammals and birds are problematic. Therefore, for
such an analysis, data on hibernating species are used, whose body
temperature can fluctuate significantly under natural conditions.
Recently, we have developed a composition of drugs capable of initiating
a long-term and stable pharmacologically induced torpor-like state
(PITS-composition). In experiments on rats, it was shown that after
intravenous injection of the PITS-composition, there was a 16–17-hour
decrease in body temperature by 7–8 ºC at the ambient temperature of
about 22ºC to 23ºC. Then, the animals came out of torpor, and their body
temperature returned to the original level without the application of
external heating. In this work we aim at analyzing E in order to
determine to what extent hypothermia induced in rats with
PITS-composition is similar to that in naturally hibernating animals.