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.