Antihypoxic effects of a thiazolidine derivative – a substance Les-589 (potassium salt of 3-(5-phenylpropenylidenrhodanine-3-yl) -propionic acid), based on the analysis of heart rate variability (HRV) of rats under hypobaric hypoxia were investigated. Conditions of hypobaric hypoxia were developed in a pressure chamber during 1 hour, identical of those at 6000 m above sea level, 45 minutes after administration of Les-589 at a dose of 100 mg/kg. As a reference drug was used thiotriazoline, injected at a dose of 2 mg / kg body weight (2,5% aqueous solution, i.m.).

3 hours after injection of the substance Les-589, also as after administration of thiotriazoline, a significant increase in values of the spectral components of HRV, comparing their initial levels, and statistical indices were observed that indicates an activation of the parasympathetic nervous system and other parts of regulatory systems. One day after administration of Les-589 most of studied spectral and statistical parameters were returned to normal ones, while in the period after the administration of thiotriazoline were observed an maintaince of a high level in activity of regulatory systems with the tendency to its reduction.

90 min after hypoxic exposure a reduced activity of all parts of regulatory systems comparing to initial level in all animals, considering the reduction of spectral and statistical indices of (HRV), were found. These changes were less pronounced in rats, which preliminary were administered with Les-589. During the term of posthypoxic period, on the background of thiotriazoline injection, significantly higher levels of all spectral parameters, to the greatest extent a power of spectrum in the range of high-frequency oscillations, both in hypoxic and control conditions were observed. It indicates a favorable course of posthypoxic adaptive rearrangements that comprise activation of energymobilizing and recovery processes under the preliminary administration of the subjected substances.

One day after development of hypoxia a partial recovery of indices on the background of an increase of heart rate were observed. During the posthypoxic period in animals after injection of Les-589 a recovery and even exceeding the initial parameters on a background of a heart rate decrease were recorded. In the group, which received a preliminary administration of thiotriazolin, 1 day after hypoxic exposure, an activity of all parts of regulatory systems was maintained at the same high level as in the previous period of posthypoxic period. It significantly exceeds the corresponding spectral parameters of HRV in animals, which were subjected to the influence of the hypoxia only. Thus, the preventive injection of Les-589, also as the reference drug thiotriazoline under conditions of hypobaric hypoxia optimizes the state of all parts of regulatory systems. After one day of posthypoxic period it appears as a moderate activation of the parasympathetic, sympathetic, humoral and metabolic regulatory impacts. Increasing of the level of activity of the sympathetic nervous system enhances the level of energogenesis, necessary to support the development of appropriate adaptive processes in response to hypoxia. HRV investigation is an informative test to analyze the nature of posthypoxic adaptation, so it can be used to assess the effectiveness of implementation of potential antihypoxants as a means of substantiated pharmaceutical correction.

Ключові слова: antihypoxants, thiazolidine derivatives, heart rate variability, experimental animals

Повний текст: PDF (Ukr)

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