Correction of acute and chronic stress disorders based on inhalation of therapeutic doses of Xenon

STATE RESEARCH CENTER OF THE RUSSIAN FEDERATION

"INSTITUTE FOR BIOMEDICAL PROBLEMS"
OF RUSSIAN ACADEMY OF SCIENCES

STATE RESEARCH AND TEST INSTITUTE
OF MILITARY MEDICINE OF THE MINISTRY
OF DEFENSE OF THE RUSSIAN FEDERATION

CENTRAL CLINICAL HOSPITAL
OF THE RUSSIAN ACADEMY OF SCIENCES
ACADEMY OF MEDICAL AND TECHNICAL SCIENCES
LLC "AKELA-N 

Method of correction of acute and chronic stress disorders based on inhalation of therapeutic doses of medical xenon mark xemed® 

Methodology of correction of acute and chronic stress disorders

The developed technology for the correction of stress-induced disorders was tested on healthy volunteers - participants of the research program, as well as on various groups of patients who were in a state of acute or chronic stress: patients with manifestations of chronic psycho-emotional stress; volunteers of various age and social groups exposed to factors, simulating a stress response in healthy individuals; operators of complex technical systems; soldiers with a low level of neuropsychic stability and a high suicidal risk; flight crew.

The presence of psycho-emotional stress in the above-mentioned groups of subjects was confirmed by the conclusions of psychologists and psychotherapists, as well as physiological testing results.

The total number of subjects was more than 200 people, and the number of procedures performed was more than 600.

Immediately before and after each procedure of inhalation of KseMed® in therapeutic doses, as well as in 24 hours after the end of the experiment, the subjects underwent a complex physiological examination, including a structured interview, filling in the SAN (SAN test name derives from the first letters of the words: S - well-being, A - activity, N - mood in the Russian language, translator's note) and Spielberger-Khanin questionnaires, Zung depression scale, evaluation of simple and complex sensorimotor reactions and reactions to a moving object, the registration of complex indicators of hemodynamics, respiration and encephalography. Besides that, during the procedure, the biopotentials of the cerebral cortex, respirations, and heart contractions were registered in the on-line mode.

The results of the study. According to the obtained results, the xenon inhalation procedure has a weak stimulating effect on the circulatory system, which is manifested by a statistically significant increase in the main parameters of the circulatory system. Thus, in the conducted studies, after the procedure the mean blood pressure (mBP), systolic blood pressure (SBP), total peripheral resistance (TPR) increased by an average of 4.1% (p≤0.01), 5.1% (p≤0.01), and 2.5% (p≤0.01), respectively.

After inhalation the stroke volume (SV) increased by an average of 12.1% compared with baseline values. Over the next 1.5-2.0 hours, the studied parameters returned to their initial values. No statistically significant increase in diastolic blood pressure (DBP) was detected, and the heart rate (HR) decreased by an average of 9.8% (p≤0.01) compared with the initial values and remained unchanged for 3-4 hours. This may be explained by the reaction of the cardiovascular system to some patient's efforts during inhalation via a closed circuit. Besides, the inhalation of therapeutic doses of xenon is accompanied by a feeling of mild euphoria, which also has, to a certain extent, a stimulating effect on the cardiovascular system.

Analysis of heart rate variability during the procedure revealed a significant decrease in the vagosympathetic index by an average of 60% (p≤0.01) during the direct inhalation of xenon, while already 30 minutes after the completion of the experiment, the value of the indicator did not differ practically from the background values. At the same time, for another 3-4 hours, the power of the low-frequency part of the HRV spectrum and the high-frequency component remained above the initial values by an average of 74% and 69%, respectively.

It should be noted that the increase in vagosympathetic index indicates the presence of stress of varying severity in a person. This is explained by the fact that under psychoemotional tension an increase in the low-frequency component of the HRV spectrum occurs, while the high-frequency component remains practically unchanged. On the contrary, the state of pleasure causes a simultaneous increase in both components, and the vagosympathetic index remains almost unchanged, or decreases below the baseline. Such changes were observed in the conducted studies. In addition, after xenon inhalation, there was a reduction in root-mean-square deviation of the RR interval by an average of 37% (p≤0.01) compared to baseline values, which also indicated a decrease in the degree of neuropsychotic tension in patients after the procedure.

Analysis of the EEG also revealed significant changes in the bioelectrical activity of the brain. In the background period, polymorphic activity of various amplitudes was noted with the presence of alpha, beta, theta and delta waves. This is because the electroencephalogram reflects the dynamic processes occurring in the brain, so even in the absence of any external stimuli, significant changes in the form of synchronization, desynchronization, and temporal asymmetries due to spontaneous fluctuations in the level of functional activity during registration are observed. Then, when applying xenon to the respiratory circuit, an increase in slow-wave activity in the spectral EEG was noted. Their localization was most typically observed in the frontal lobes, mostly on the left, although the pattern of zonal rhythm changes was often absent even in the same subject with repeated procedures. During the procedure, a decrease in the spectral severity of the alpha rhythm was noted, while its spread to the frontal leads was observed. After completion of the procedure, the most pronounced alpha rhythm remained in the occipital lobes of the brain. It should be noted that in almost every case of xenon inhalation physiological phenomena were observed, which indicated an alteration of consciousness of the test subjects. Altered states of consciousness (ASC) are a new, actively developed field of interdisciplinary researches. According to N.P. Bekhtereva and L.I. Spivak ASC should be understood as one of the common, though not fully optimal, strategies of active adaptation of a normal person to unusual conditions, which consists of the temporary induction of a number of unusual mental phenomena. Audiovisual illusions, spatial depersonalization and a decrease in the suggestion threshold can be attributed to such phenomena, which were observed during xenon inhalation in subnarcotic doses.

Analysis of trends in the electrical activity of the brain during experiments allows us to draw a certain analogy with the corresponding dynamics during sleep. The state of the subjects in the process of inhalation can be characterized in essence as a kind of dreamlike state with preservation of volitional control. This determines the main features of the similarity between the EEG of sleep and the EEG of altered states of consciousness. As with ordinary sleep with dreams, the intensification of the EEG- power of the delta and theta rhythms occurs simultaneously with the moving of zones of slow-wave activity between both hemispheres, as well as the occurrence of alpha activity foci in the occipital lobes, mostly on the left.

Currently, it is believed that the alpha rhythm is determined by the thalamo-cortical neural networks and determines the interaction of the subject with the outside world. Those unusual subjective sensations that volunteers experienced during xenon inhalation were caused by fixation on their own internal sensations. Although the increase in slow-wave activity is considered by most researchers as a sign of a decrease in the functional state of the brain, in this case it should be considered as a consequence of an increase in "internal concentration" and a disconnection of attention from the external environment due to the activation of cortical projections on the thalamus.

Thus, the intensification of the spectral power of the low-frequency components of the EEG with a decrease in alpha-rhythmic activity indicates shifts in the activity of subcortical structures, particularly in reticulo-thalamocortical interactions.

The observations made during the carrying out of this work have identified the specific features of the bioelectrical activity of the brain during xenon inhalation. The most important of them is the complete preservation of awareness and volitional control during the process, which allows us to draw an analogy with the "controlled", "conscious sleep." In addition, it was noted that xenon inhalation performed a number of restorative functions of sleep. Evaluation of the quality of operator activity and the results of psychological questionnaires show an improvement in the functional state of the test subjects, which will be discussed later. Given the time required for inhalation, it can be concluded that the restorative efficiency of the inert gas far exceeds daytime sleep.

At the end of the procedure, a gradual decrease in the spectral power of slow-wave activity for 5-15 minutes was observed, which was accompanied by a gradual return to the usual state of consciousness. However, the spectral expression of the delta rhythm remained above the baseline values for another 20-30 minutes.

Conclusions

 Normalization of the neurovegetative regulation of body systems and improvement of the picture of the bioelectrical activity of the cerebral cortex led to an improvement in the subjective state of patients. After xenon inhalation respondents subjectively more highly evaluated their condition. In particular, the "Mood" integral indicator increased by an average of 9.5%, and the "Well-being" indicator increased by 11.4% (all changes were significant at the 5% level). In addition, a statistically significant reduction in the level of situational anxiety by more than 40% was an important effect of inhalation.

These studies indicate the high efficiency of the technique and perspectives of its use for correction of acute and chronic stress disorders, and also as a component of the complex therapy of a number of diseases that have a psychosomatic etiology.