Antihypoxic effects of derivative on the EEG power spectra in rats with different susceptibility to oxygen deficiency

Abstract

The succinate-containing hydroxypyridine derivative yancarb increases both the altitude tolerated by rats and their survival time at a high altitude, particularly in rats with low resistance to hypobaric hypoxia; it also prevents both phasic changes in the EEG characteristic of hypobaric hypoxia and hemispheric asymmetry and paroxysmal activity in the brain of highly resistant rats in the 5000-10,000 m range and in rats with low resistance in the 5000-11,000 m range. Antihypoxic effects of this substance are more pronounced in low-resistance rats and in the left hemisphere of both high-and low-resistant animals; in altitude range of 10,000-13,000 m these effects are weaker or absent. Key Words: cerebral cortex; Fourier EEG power spectra; hypobaric hypoxia; antihypoxants; succinate-containing hydrooxypyridine derivativeHypoxia inhibits the major NAD-dependent pathway of oxidation in the respiratory chain, particularly in the brain [1,2], which may impair the energy-synthesizing function of the cell. Under such conditions activation of alternative metabolic pathways providing energy for the respiration (for example, the succinate oxidase oxidation pathway), may be effective against hypoxia [1,2,6]. Verification of this possibility showed that succinate-containing compounds of the hydroxypyridine series (mexidol) increase the tolerance to acute hypobaric hypoxia [3,6]. Further investigations of the mechanisms of action of mexidol showed that its protective effects are due to activation of the succinate oxidase oxidation pathway and utilization of the succinate molecule as the energy substrate [3,6]. In this study we examined the effect of the hydroxypyridine derivative yancarb on survival of rats after acute hypobaric hypoxia and on the specific changes in EEG power spectra in the cerebral cortex. MATERIALS AND METHODSMale random-bred rats (body weight 180-200 g) were used. They were divided into two groups according to the resistance to hypoxia: high and low (HR and LR, respectively) [5]. Electrodes were inserted and EEG recorded in unrestrained animals as described previously [4].Control rats were placed in a flow altitude chamber, and EEG was recorded for 4 min before "elevation" (baseline EEG) and then at an altitude of 5000, 8000, 9000, 10,000, 11,000, 12,000, and 13,000 m. On each altitude the rats were left for 4 rain (8 rain at 11,000 m). Total period of elevation ranged from 25 to 35 min, depending on the time when agony began. At an altitude of 11,000 m, two 4-min EEGs were recorded. Experimental rats were injected with yancarb (40 mg/kg intraperitoneally) 20 min before elevation, and the EEG was recorded 15 min aRer the injection, after which EEG was recorded as in the control rats [4]. An additional EEG was recorded at 12,000 m in LR rats and at 13,000 m in HR rats because the hypoxia threshold was raised by yancarb.