Some Problems of Neuro-endocrine Regulation

Study of endocrine influences on the process of dying and re­suscitation has attracted more and more attention in recent years. In the United Kingdom many scientists have been working on this problem. Their investigations have established that the initial functional capacity of the endocrine system and the complex of neuro-endocrine reactions greatly control the course of the terminal state and the possibility of subsequent res­toration of the organism’s functions. 

Thus, it has been shown that an increase in the blood level of thyroid hormone accelerates the process of dying from loss of blood; but whereas lengthy saturation of the organism by these hormones hampers resuscitation even after only two or three mi­nutes of clinical death, a single injection of a large dose of 1-thyroxin six hours before the terminal state promotes stable res­toration of all the organism’s functions even after seven minutes of clinical death. The literature and our own findings give grounds for believing that the acceleration of the extinction of vital func­tions observed in cases of hyperthyroidism is due to a reduction of resistance to hypoxia.

There is no doubt that, when animals are fed thyroid hormones for a long time, the deep changes in all the organs and systems that accompany hyperthyroidism affect the process of dying and particularly of resuscitation, above all the disturbances in the cardiovascular system. The posi­tive effect of a single injection of thyroxin is apparently due to activation of a number of the organism’s systems and is probably one of its forms of defence against harmful influences. The in­crease in metabolic processes in particular would obviously pro­mote more rapid neutralization of toxic products as well as more rapid dying. Its favourable effect on the outcome of resuscitation may also be due to activation of the functioning of the adrenal cortex and of the pancreas.

With hypothyroidism the picture is quite different. The in­crease in the organism’s resistance to hypoxia in thyroid animals was expressed in a depressing of processes of dying and a statisti­cally reliable improvement in the outcome of resuscitation after protracted clinical death but a brief period of dying. The favou­rable effect of hypothyroidism is apparently due to a slowing down of metabolic processes. Confirmation of this can be found in the increased resistance to hypoxia that the organism displays during hibernation or in conditions of deep hypothermia, and when inhibitors of oxidation are employed.

Dynamic determinations of the protein-bound iodine content of blood plasma in dogs by Barker’s method with the Stepanov’s modification in standard experiments made it possible to assess the peculiarities of thyroid secretion during dying and subsequent resuscitation. Judging from the PBI level, the state of tension that arises in animals while they are being prepared for experiment depresses thyroid function. The PBI content remained practically unchanged during death either from blood loss or electric shock and during the begin­ning of resuscitation. Six hours after the restoration of cardiac activity, however, depres­sion of thyroid secretion was observed in some of the dogs while it increased in others. Analysis of these findings showed that, independently of the cause of death, depression of thyroid function invariably went with a favourable course of resuscita­tion, while an increase was only observed when severe hypoxia provoked disturbances of the central nervous system and in un­favourable outcome.

Investigations of the glucocorticoid function of the adrenal glands during dying of various aetiology and subsequent reanimation showed that functioning of the central nervous system was fully restored after clinical death only in those animals in which the initial functional level of the adrenal cortex was high, ensur­ing maintenance of a high 17-oxicorticosteroid content in the plasma during dying and in the early restorative period. A high glucocorticoid content in the organism during dying and the earlier restorative period had a defence effect as re­gards the central nervous system in conditions of hypoxia. But in some animals with high reactivity of the adrenal cortex an inhibi­tion of the processes of dying was noted, which had an unfavourable effect on the course of the postreanimation period. On the other hand complete resto­ration of the vital functions of the organism was impossible in dogs with an initial relative deficiency of glucocorticoids.

When the hypophysis and the adrenal gland were removed be­fore the experiment, the course of the terminal state was notably worse, the ogranism’s sensitivity to hypoxia was increased, and restoration of functions in the revived organism hampered. A high glucocorticoid content during dying and in the early reanimation period evoked a defence reaction as regards the central nervous system which was still in a state of hypoxia.

Other endocrine glands also have a certain effect on the course of dying and reanimation. Insulin insufficiency, for example, hin­ders resuscitation, and prior administration of insulin increases the effectiveness of reanimatory measures. Castration of males a month prior to the experiment accelerates the restoration of vital functions, but a year’s interval hinders resuscitation. The admini­stration of androgens to intact animals facilitates a more rapid resuscitation.

The state of many endocrine glands in the postreanimation pe­riod, it should be noted, is closely linked with the character of the restoration of central nervous function. A favourable early post­reanimation period is accompanied with inhibition of secretion by the adrenal cortex and the thyroid gland. With severe neurological disturbances in the posthypoxic period there is an excess sympatho-adrenalin reaction and pro­tracted activation of the hypophysis-adrenal cortex system and of the hypophysis-thyroid gland system. The leading role in the en­docrine reaction would seem to be that of the sympatho-adrenalin system as the defence and tension apparatus has developed in connection with and on the background of this system. Laborit et at. and Adams-Ray have reported severe disturbances of sympathetic innervation in cases of pro­longed shock developing as a result of exhaustion of the noradrenalin reserves of the tissues. Administration of 1-thyroxine — the precursor of the catecholamines — eased the course of shock con­siderably.

It is not excluded that the subcortical formations may also have a modulatory influence on endocrine reactions. The increase in plasma glucocorticoid concentration that occurs when the course of the restorative period is severe coincided in time, as a rule, with considerable posthypoxic activation of the amygdaloid com­plex of the brain. Bearing in mind the involvement of the amygda­loid nucleus in central nervous regulation of the functions of the hypothalamus-hypophysis-adrenal cortex system, it would appear that the increase in adrenal cortex function observed during severe course of the postreanimation period is a result of the amygdaloid nuclei’s influence on the endocrine functions of the hypothalamus.

Our research enabled us to trace some ways of treating insuf­ficiency of endocrine glands. In particular, clarification of the role of pancreatic incretory function in shaping a favourable reaction of the hypophysis-adrenal cortex system in posthypoxic states al­lowed us to use a complex of hormones to correct hypoxia-provoked disturbances after clinical death. Administration of these hormones ten to twenty minutes and six hours after 15 minutes of circulatory arrest provoked by ventricular fibrilla­tion due to electric shock improved the results of resuscitation.

The administration of hydrocortisone during the terminal state and in the postreanimation period, it is important to note, causes a reliable improvement in the outcome of resuscitation after pro­tracted clinical death in animals with high functional capacity of the adrenal cortex. Given to animals with an initial relative in­sufficiency of glucocorticoids it delayed the onset of clinical death.

Thus there is no doubt of the importance of the endocrine system in realization of the organism’s defence and compensatory reac­tions during dying and resuscitation. Further research will help us to determine the correlation between the reactions of the en­docrine glands during terminal states and to clarify the neuro­humoral inter-relations that exist in these conditions, which will permit wider and more rational use of hormone preparations in the prophylaxis and treatment of agony and clinical death.