CATECHOLAMINE METABOLISM IN HUMANS UNDER ACUTE AND CHRONIC ACTION OF HYPERBARIC OXYGENATION

The human body has been subjected to hyperbaric oxygenation (HBO) in specific productive activity (underwater work and research) and as a means of therapeutic treatment. Experimental data and clinical observation show that HBO induces increase in the content of dissolved oxygen in blood and activation of mitochondria regeneration, cellular metabolism and stimulation of enzymes of the respiratory chain and glycolysis; energy formation in the tissues of brain, heart, and liver; and the content of some hormones and mediators in tissues and blood changes; i.e. stress reactions are observed (Kreps, 1981; Shimkevich, 1981; Ratner and Kvetnoy, 1981). Yet, data on the state of the sympathetic adrenal system (SAS) after the action of therapeutic doses of HBO are insufficient. It has been shown that the activity of monoaminoxidase (norepinephrine [NE] substrate) in rat brain tissues increases (Gorkin, 1981). It is, however, known that CA metabolism in the body depends also on the activity of some other oxygen-dependent enzymes in tissues.

The object of this paper was the study of acute and chronic HBO action (2 Atm, 60 min) on CA metabolism in the course of therapy after various initial states, in the human.

The urinary excretion of free forms of С A and DOPA, С A sulfates, free forms of metanephrine (MN) and normetanephrine (NMN) in separate samples of the waking and sleeping periods were studied by fluorometric methods, and that of the main С A metabolites—VMA and VA by col-orimetry after their chromatographic separation.

To ensure more precise estimation of CA metabolism, both excretion of the total of CA-type substances studied in the circadian cycle (general SAS secretory activity) and at the selected periods during the 24 h were calculated. To estimate the qualitative shifts in CA metabolism, values of CA metabolite ratios were studied (Bolshakova, 1975). The data were treated statistically; Student's criterion was determined.

Three groups of people were studied: 1) 9 healthy males, ages 18-20 under normal conditions of life and work (single application of HBO); 2) 35 males, ages 20-29, undergoing treatment for duodenal ulcer (12 applications of HBO); 3) 15 patients (7 males, 8 females), ages 18-45. HBO was applied in the complex treatment of the medium-severe and severe forms of diabetes mellitus.

The effect of the acute (first) application of HBO combined with the inescapable emotional stress factor due to unfamiliar stimulus produced the following results:

The 1st group (healthy subjects) exhibited no differences in the level of the mean circadian cycle excretion of all the substances under study and in the general secretory SAS activity between the initial state (24 h without HBO application and at the testing period (1 HBO application within 24 h). Yet, pronounced synchronization of the secretion peaks of all the CA-type substances after HBO application was noted. The increase in NE:DA (on 250%), VMA: (MN + NMN) (on 200%) coefficient was observed (Fig. 1,A,II; 2,A,II).

In the 2nd group, acute HBO application produced greater synchronization of the CA-type substances excretion without any verifiable shifts, against the background of increased excretion of NMN in urine, with other indices being within the norm at all time. (Fig. 1,B,II; 2,B,II).

In the 3rd group, the first HBO application decreased secretory SAS activity over the 24 h period two-fold, reduced the evening peak of CA excretion; synchronized excretion of all substances at the period of HBO application; and, as in healthy subjects, NE:DA (170%) and VMA: (NM + NMN) (250%) coefficients increased. All this went against the background of quantitative disturbance (considerably greater activation of free, conjugated CA forms and metabolites) and the presence of two peaks of SAS activity within 24 h (pronounced peak of DA and HVA excretion in the evening). (Fig. 1,C,II; 2,C,II).

Thus, the first HBO application reveals its stress effect (possibly enhanced by emotional stress), which is manifest in elevated level of excretion of С A and their metabolites, synchronization in the excretion peaks, and activation of synthesis and CA metabolism.

Figure 1.24 hour urinary excretion of DOPA, DA, NE, E, MN, NMN (nM/24h), VMA, HVA (μM/24h) in healthy subjects (A) and patients with duodenal ulcer (B) and diabetes mellitus (C) under hyperbaric oxygenation (HBO) treatment (2 Atm; 60 min). Time of treatment HBO: I — before HBO treatment; II—1st session HBO (▲); III—after 12 sessions HBO. Significant difference at level healthy subjects are denoted by *), at basal level — **) (p < 0.05).

Figure 2. Orcadian rhythms of DOPA. DA, NE. E. MN, NMN (pM/min), VMA, HVA (μM/min) excretion in healthy subjects (A), patients with duodenal ulcer (B) and diabetes mellitus (C) under HBO treatment.

Time of treatment HBO: I -before HBO treatment; II-1st session HBO (▲); III-after 12 sessions HBO. Time of day: 1 - 7-11 hrs; 2-11-22 hrs; 3 - 22-7 hrs; 4-7-10 hrs; 5-Ю-12 hrs; 6-12-17 hrs; 7-17-23 hrs; 8 - 23-7 hrs; Significant difference at level healthy subjects are denoted by *), at basal level - **) (p < 0.05).

In the case of the initial acute disturbance of CA metabolism (the 3rd group), the effect of HBO decreases tissue hypoxia and brings С А metabolism back to normal circadian cycle. In the case of the little-affected CA metabolism (the 2nd group), only some features of this reaction, such as the synchronization of CA excretion at the moment of HBO application, are observed.

In the second group, the prolonged action of HBO (12 applications) revealed varifiable decrease of HVA, VMA, MN excretion level both at various periods of the 24 h and for the 24 h generally, which prompted the decrease of general secretory SAS activity as compared to its initial value. When the treatment was effective, more pronounced normalization of CA metabolism was observed; in the absence of the favorable effect, NE metabolism and its O-methylation processes were disturbed (Fig. 1,B,III; 2,B,III).

In the 3rd group (12 HBO applications), the initial changes in CA metabolism were gradually restored after the treatment regardless of the therapeutic effect, i.e. the nightly peak of CA excretion (DA and HVA to a greater extent) appeared; the level of general secretory SAS activity in the circadian cycle increased, but these indices were smaller than the initial values (Fig. 1,C,III; 2,C,III).

Consequently, the repeated action of HBO led to adaptation to HBO effect and the initial acute stress effect was not observed. At the retention of the etiological factor which causes С A metabolism disturbance, the normalizing HBO action is manifest only at the HBO period.

Metabolic processes due to hypoxia and its disappearance in tissues possibly affects С A metabolism, both indirectly thanks to changes in tissue metabolism, and directly, affecting synthesis, metabolism and CA excretion in chromaffin and sympathetic nervous tissues, as well as central regulatory CA metabolism mechanisms. The changes in the level of excretion of CA and their metabolites may be due to various degrees of activation of such enzymes of synthesis and CA catabolism as tyrosin-hydroxylase, dopamine-β-hydroxylase, MAO, COMT.

The analysis of individual reactions to acute HBO action in healthy subjects shows the dependence of the reaction on the degree of adaptation of the body to other physical factors. Those with a great degree of adaptation exhibit no reaction of CA metabolism on HBO application.

Thus, the effect of the first HBO application affecting metabolic processes in tissues causes pronounced stress influence on CA metabolism after its application in therapeutic treatment. Its prolonged application leads to the adaptation of SAS.

Activation of CA secretion and metabolism following the first use of HBO in 9 healthy subject and in 35 patients with duodenal ulcer has been shown, as well as a return to normal of the disturbed circadian rhythm in severe forms of diabetes (15 patients), and a lowering of the pathologically-elevated CA excretion level. Synchronization of secretion peaks of all the CA-type substances was noted both in healthy subjects and patients during the period of HBO influence. At the moment of its application, HBO has a stress effect on the organism. Daily HBO action over prolonged periods (12 days) results in an adaptation of the CA metabolism to this influence and in a tendency for all the quantitative and qualitative metabolic indices to return to their original pathological levels. However, it normalizes pathologically elevated metabolism in cases of pronounced tissue hypoxia by affecting the processes of CA synthesis and inactivation.

References

• Bolshakova, Т.О. (1975) Certain aspects of catecholamine metabolism in man under stress. In; Catecholamine and Stress, edited by E. Usdin, R. Kvetnansky and I. Kopin, Pergamon Press, Oxford, pp. 589-592.
• Gorkin, V.Z. (1981) Amine oxidases: Medical aspects. Medizina, Moscow, pp.336.
• Kreps, E.M. (1981) The effect of pressure of biochemical process in organism.
• In: Proceedings of the VII International Congress on Hyperbaric Medicine, Moscow, pp. 377-378.
• Ratner, G.L. and Kvetnoy, I.M. (1981) APUD-system and hyperbaric oxygenation: Theoretical and applied aspects, In: Proceedings of the VII International Congress on Hyperbaric Medicine, Moscow, p. 390.
• Shimkevich, L.L. (1981) General regularities and some mechanisms of hyperbaric oxygen action on organism. In: Proceedings of the VII International Congress on Hyperbaric Medicine, Moscow, p. 383.