Стресорні механізми гострої крововтрати та їх фармакологічна корекція в експерименті

Abstract

В експериментах на білих щурах показано, що гостра крововтрата із вилученням 25% циркулю- ючої крові супроводжується формуванням тріади Сельє з гіпертрофією надниркових залоз, інволюцією тимусу й слабким ушкодженням слизової оболонки шлунка. Максимально виразні порушення показників «червоної» крові припадають на стадію тривоги, а їх відновлення – на стадію резистентності стрес-синдрому, викликаного вилученням крові. Стреспротективні засоби мексидол (100 мг/кг) і натрію оксибутират (100 мг/кг), введені за 30 хвилин перед крововтратою, попереджують повномасштабну активацію стрес-реалізуючих систем, що підтверджується меншою виразністю тріади Сельє, і послаблюють вияви постгеморагічної анемії. В экспериментах на белых крысах показано, что острая кровопотеря с удалением 25% циркулирующей крови сопровождается формированием триады Селье с гипертрофией надпочечников, инволюцией тимуса и слабым повреждением слизистой оболочки желудка. Максимально выраженные нарушения показателей «красной» крови приходятся на стадию тревоги, а их восстановление – на стадию резистентности стресс-синдрома, вызванного потерей крови. Стресспротективные средства мексидол (100 мг/кг) и натрия оксибутират (100 мг/кг), введенные за 30 минут до кровопотери, предупреждают полномасштабную активацию стресс-реализующих систем, что подтверждается меньшей выраженностью триады Селье, и ослабляют проявления постгеморрагической анемии. Blood loss is a complex of compensatory and pathological reactions that arise in response to bleeding. Changes in the body’s functions in acute blood loss have universal adaptive, or more precisely, compensatory character. The basis of adaptation and compensation are the same mechanisms, in particular, stress-realising systems. Limiting their activity by inhibitors of the central nervous system is the essence of the classical protection of stress, but its role in the modifying of compensatory reactions in blood loss is not sufficiently investigated. Research aim is to study the influence of drugs with stress-protective properties on the development of compensatory reactions in acute experimental blood loss. Object and methods. Experiments were performed on 99 albino male rats, which have been undergone acute blood loss and its pharmacocorrection with mexidol (100 mg/kg, intraperitoneally) or sodium oxybutyrate (100 mg/kg, intraperitoneally) administered 30 min prior to hemorrhage. Acute blood loss was modeled by puncture of the heart and extracting 25% of circulating blood under ketamine anesthesia. The volume of drugs solutions or isotonic sodium chloride solution, which was administered to rats with control pathology, ranged from 0.8 to 1 ml, depending on the individual weight of the animal. In all series of experiments, the study was performed at 3, 24 and 72 h and 5 days after the moment of blood extraction. Animals were taken out from the experiment by authanasia under the ketamine general anesthesia. Each series had a group of intact animals (control). The masses of thymus and adrenal glands were determined and their weight coefficients were calculated. Presence of ulcers in the stomach was evaluated, their frequency and multiplicity were calculated. In the blood, red blood cells count, hematocrit and total hemoglobin were determined. The probability of the difference between the groups was estimated using a single-factor ANOVA dispersion analysis with Fisher’s LSD aposteriori test. Results and discussion. Acute blood loss is accompanied by hypertrophy of the adrenal glands, involution of the thymus and formation of ulcers in the stomach of animals, although the ulcers occur only within 72 h after the blood extraction. The maximal changes in general-somatic parameters are registered 24-72 h after the blood loss. Mexidol’s administration prevents the development of typical stressoric general-somatic changes, that manifests itself the most consistently 24 h after the start of experiment. This pharmacodynamic effect is similar to the effect of sodium oxybutyrate.Acute blood loss is accompanied by a decrease in red blood cells count, hematocrit and total hemoglobin in the period from 3 to 72 h and their recovery in 5 days after the blood extraction. In acute blood loss, the investigated drugs with stress-protective activity not only prevent the development of general-somatic changes, which are characteristic for the activation of stress-realising systems, but also reduce the appearance of anemia caused by the blood extraction. Conclusion. Consequently, we have confirmed that acute blood loss has classical signs of stress reaction and is a separate case of general adaptive syndrome – anemic, or erythropoietic stress. Reflex compensatory reactions and hydremia in acute blood loss coincide with the anxiety stage of the general adaptive syndrome, and bone marrow compensation – with the stage of resistance. The activation of erythropoiesis, in general, is typical for this stage of the stress syndrome, but in anemic stress it becomes particularly expressive. Positive effects of mexidol and sodium oxybutyrate on adaptive-compensatory response in acute blood loss can be explained by the inhibition of central links of the stress reaction and the accelerated connection of erythropoietic compensation mechanisms. Such results are in the agreement with the literature data on less severity of blood loss and hemorrhagic shock in the background of the action of morphine or ethyl alcohol.