Results
It has been shown previously that after injection of the PITS-composition, the rat body temperature decreased by about 7.5 ˚C, while the half-width of the temperature curve was about 16.5 h, at ambient temperature of 22˚C to 23˚C (Fig.1). For comparison, we investigated the effect of anesthetic xylazine, which is also able to reduce the body temperature of animals, often in combination with ketamine . In our experiments, xylazine initiated a decrease in the rat body temperature by about 5.5 ˚C, at ambient temperature of 22˚C to 23˚C.The half-width of the temperature curve was about 3 hours (Fig.1).
It has been shown previously that after intravenous injection of PITS-composition, there was a reversible decrease in metabolic rate and body temperature. Both parameters changed almost simultaneously (Fig. 2). We used these data to compare E in a pharmacological and natural torpid state (Fig.3). It has been found (Fig.3) that in the pharmacological torpor lasting typically one day in rats (Rats-PITS),E = -0.56±0.03 eV which was close to the corresponding value in daily heterotherms E = -0.57±0.04 eV. In true hibernators, this value was significantly higher (E = -0.80±0.04 eV), while in anesthetized animals it was significantly lower (E = -0.17±0.071 eV). In addition, in rats treated with xylazine, the small value of the coefficient of determination (r2 = 0.12) indicates a wide spread of the experimental points and poor quality of the regression model. Therefore, it is necessary to evaluate in more details how the metabolic rate depends on the temperature during anesthesia with xylazine.
The analysis shows (Fig.4A) that in the presented experimental data obtained on rats anesthetized with xylazine there was a time lag between the temperature curve and the heat production curve. The question arises whether this lag could be a reason for low E andr2 values? We have found that a significantly better coincidence of the curves was observed when the heat production curve shifted by Δt = 1 hour (Fig.4A). In addition, to confirm this assumption, we performed a numerical shift of the heat production data (Fig. 4B) and find the imaginary dependence of E on the shift (Fig.4C). The minimal E was observed at the shift Δt= 1 hour and considered the corrected Ec=-0.67±0.11 eV, which in this experiment corresponded to two intervals between measurements: Shift +2 (Fig.4 D). It should also be noted that as a result of the shift, the coefficient of determinationr2 increased significantly from 0.12 (Fig.3A) to 0.70 (Fig.4 C), which indicates an improvement in the model of regression analysis.
Since in homeothermic animals, the change in the body temperature occurs as a result of changes in heat production, the lag between the temperature and the heat production is associated with a limited rate of the body heat conductivity and heat dissipation. Therefore, it takes a time (Δt ) to achieve a balance between the metabolic rate and the body temperature. This nonequilibrium situation could be the reason of an incorrect estimation of E . The correctedEc = -0.68±0.17 eV obtained at the imaginary numerical Shift+2 (Fig.3) is significantly (p < 0.0001) larger than that, obtained (Fig.3), in daily heterotherms (E = -0.57±0.04 eV) and in artificial hibernation, lasting for a day (E = -0.56±0.03 eV), but smaller than that in true hibernators (E = -0.8 eV), hypothermia of which lasts for weeks and even months.
The influence of the imaginary shift on the E was studied on rats after injection of the PITS-composition (Fig. 5). In this case, the minimal E was obtained without any shift (Shift 0), which indicated the state of equilibrium between heat production and heat dissipation during pharmacological torpor, which was significantly longer than that in anesthesia.