ENDOTOXINEMIA, DYSREGULATION AND THE PRE-ILLNESS FORMATION

Abstract

The study of the conditions of pre-illness and early stages of the disease, as well as their mechanisms, are of particular relevance for modern preventive medicine. It is known that dysregulation is the basis of many pathological processes, the leading link in the pathogenesis of which is endotoxinemia, the severity of which is largely determined by the state of detoxification liver function. The aim of the study was to elucidate the significance of the liver detoxification function and endotoxinemia in the occurrence of dysregulation and the pre-illness formation. In experiments on rats and rabbits it was is established that the direction and nature of changes in the processes of heat exchange, energy and plastic supply of the organism, their hormonal and humoral regulation under the action of E. сoli endotoxin (LPS) depend on the severity of endotoxinemia, the state of detoxification liver function. It is shown that in conditions of functional liver failure, the action of LPS in the body in trace concentrations is accompanied by an increase, and with severe endotoxinemia, a decrease in the activity of the processes of energy and plastic supply of the organism, detoxification. It was found that the ambiguous direction and nature of the changes in the processes of heat exchange, energy and plastic supply of the organism, their neurotransmitter, hormonal and humoral regulation under conditions of endotoxinemia depend on its severity and are largely due to a decrease in the level of arginine in blood plasma and cerebrospinal fluid. In experiments on rats it was revealed that the central action of 1-noradrenaline (10 μg) under the conditions of preliminary introduction of L-arginine hydrochloric acid (100 μg) into the brain ventricles (for 15 min) exerts a more pronounced and prolonged decrease in body temperature in comparison with control, while the duration and severity of the hypothermic effect from the introduction of acetylcholine into the brain ventricles at a dose of 2.5 μg with eserine (5 μg) decreased. It was found that in conditions of bacterial endotoxinemia, accompanied by an increase in body temperature and a decrease in the level of arginine in blood plasma and cerebrospinal fluid in rabbits, intensive utilization of 14C-arginine hydrochloric acid from tissues of the hypothalamus takes place. Endotoxinemia is a key link in the pathogenesis of disregulatory pathology and a universal factor in the development of such a condition as pre-illness.