Цель: изучить состояние микроциркуляторного русла в ответ на ежедневное охлаждение до сверхглубокой степени гипотермии у крыс. Материалы и методы: в исследовании использовались крысы-самцы линии Вистар (23 особи). Животные экспериментальных групп подвергались ежедневному охлаждению в воде температурой 5 °С до достижения сверхглубокой степени гипотермии. Анализ состояния микроциркуляторного русла проводился при помощи метода лазерной доплеровской флоуметрии с анализом амплитудно-частотного спектра колебаний кровотока на аппарате ЛАКК-02 и осуществлялся до охлаждения и сразу по достижении сверхглубокой степени гипотермии на 1, 3, 5, 10, 14-й дни. Результаты и их обсуждение. В 1-й день сразу по достижении сверхглубокой степени гипотермии регистрировалось снижение показателя перфузии с развитием вазоконстрикции и угнетением активности гладкомышечных клеток прекапилляров. На 14-й день сразу после охлаждения развилась мощная вазодилатация с застоем крови в венулах. Ключевые слова: гипотермия, микроциркуляция. THE SYSTEM STATE OF THE MICROVASCULATURE IN DIFFERENT PERIODS OF AFTER HIPOTERMIA IN RATS ON

Цель - изучение системы гемостаза при однократной иммерсионной гипотермии у крыс. Методика. Исследования выполнены на 40 крысах-самцах Wistar, массой 300 ± 15 г. Иммерсионную гипотермию моделировали путем погружения находящихся в индивидуальных клетках животных в воду с температурой 5°С при t воздуха 7°С. Критерием прекращения воздействия служило снижение у экспериментальных животных ректальной температуры до 10-16°С, что соответствовало сверхглубокой степени гипотермии. Время экспозиции было индивидуальным и составило 55 ± 5 мин. Контролем служила кровь 20 животных, подвергшихся аналогичной процедуре при температуре воды 30°C и воздуха 22-25°С. Время экспозиции соответствовало времени охлаждения животных опытной группы. В дальнейшем все животные были разделены на 4 группы. У животных 1-й группы (контроль) забор крови осуществлялся сразу после извлечения из воды. У животных 2-й группы (опытная) сразу по достижении сверхглубокой степени гипотермии. В 3-й группе - кровь забирали через 24 ч после извлечения из теплой воды (контроль). В 4-й группе забор крови осуществлялся через 24 ч после прекращения охлаждения (опытная). Результаты. Сравнительный анализ результатов показал, что сразу по окончании однократного холодового воздействия наблюдалось увеличение агрегационной активности тромбоцитов и развитие гипокоагуляционных сдвигов, снижение концентрации антитромбина III на фоне повышения концентрации фибриногена и угнетения активности фибринолитического звена системы гемостаза. Описанный гемостазиологический статус укладывается в картину формирования дистрессорной реакции в ответ на однократное действие раздражителя. Через 1 сут. после достижения экспериментальными животными критической температуры ядра в кровотоке сохранялись гипокоагуляционные сдвиги, увеличивалась концентрация фибриногена и регистрировалось появление маркеров тромбинемии. Таким образом, через 1 сут. после общего переохлаждения сохранялся риск развития состояния тромботической готовности и усиливалось состояние дистресса. Заключение. Признаки нарушения гемостазиологических свойств крови, зафиксированные сразу после прекращения охлаждения, через сутки усугубляются появлением в кровотоке маркеров тромбинемии. Aim. To study the state of rat hemostasis system during hypothermia and in post-hypothermic period. Methods. The study was performed on 40 Wistar male rats weighing 300 ± 15 g. Immersion hypothermia was modeled by placing the animals in individual cells in water at a water temperature of 5°C and an air temperature of 7°C. The criterion for terminating the exposure was a decrease in rectal temperature to 10-16°C, which corresponded to ultra-deep hypothermia. Exposure time was individual and averaged 55 ± 5 minutes. The control was the blood of 20 animals withdrawn after they had been placed in water in individual cells at a water temperature of 30°C and an air temperature of 22-25°C. The exposure time was similar to the cooling time of animals of the experimental group. Then all animals were divided into 4 groups. In the first group (control), blood was withdrawn immediately after removing the rats from water. In the second group (experimental) - immediately after reaching ultra-deep hypothermia. In the third group - at 24 hours after removing the rats from water (control). In the fourth group - at 24 hours after the end of cooling (experimental). Results. Comparative analysis of the results showed that immediately after the end of single cold exposure, the platelet aggregation activity was increased with development of hypocoagulation shifts, and the аntithrombin III concentration was decreased, which was associated with increased fibrinogen concentration and inhibition of the fibrinolytic system activity. The described hemostasiological status fits into the picture of a distress response to a single action of the stimulus. One day after the experimental animals have reached the critical core temperature, hypocoagulation shifts persisted in the blood, fibrinogen concentration increased, and thrombinemia markers emerged. Therefore, one day after general hypothermia, the risk for developing the state of thrombotic readiness remained, and the state of distress increased. Conclusions. The signs of impaired hemostasiological properties of the blood observed immediately after the end of cooling were aggravated in 24 hours by emergence of thrombinemia markers in the blood.

Hypothermia produces a generalized impact on an organism, with involvement  of all organs and systems into the response. It was shown that hypothermia promotes multi-organ dysfunction syndrome, which makes it important to study the influence of hypothermia on condition of hemostasis and microcirculatory systems. Aim. To study the condition of the hemostasis system and the microcirculatory bed in different periods of moderate hypothermia in rats. Materials and Methods. The current study was performed on 50 male Wistar rats. Condition of microcirculatory blood stream in all animals was assessed with laser Doppler flowmetry. Condition of hemostasis system was studied according to routine protocols and an integrated method of examination – thromboelastography. Statistical analysis was performed using Statistica 6.0 software package (StatSoft, USA) with calculation of Mann-Whitney nonparametric test. Results. Analysis of the experimental data showed that moderate hypothermia produced a pronounced modulating influence on the microcirculatory system. Vasodilatation occurred immediately after reaching the stage of hypothermia, suggesting the beginning of decompensation in the experimental animals. The highest risk for hemodynamic pathologies was observed 5 days after cessation of cooling and was characterized by a massive reduction in the vascular tone, intensification of hemodynamics against the background appearance of thrombinemia markers in the blood stream and pronounced inhibition of fibrinolysis. Enhanced hemodynamics of the nutritional vascular bed with the underlying progressive prothrombotic condition is a potent risk factor for thrombosis and multiple organ dysfunction syndrome. Vasospasm that developed 2 weeks after recovery of the body temperature, indicated a profound modulation of vasculature and preservation of high-level sympathetic input, as well as increasing rigidity of blood vessel walls. Rising fibrinogen concentrations confirm a progressive inflammatory reaction. Conclusion. A moderate degree of hypothermia produces a pronounced modulating effect on the microcirculation. The established regularities make it possible to form a clear understanding of the course and development of the pathological reaction in the body of victims and to give recommendations on the use of pharmacological medicine for preventive therapy. Thus, a period has been established when thrombotic readiness is maximal, and use of anticoagulant and antiplatelet drugs is required, together with drugs that improve rheological properties of blood.

Aim. To study the dynamics of indicators of microcirculation during a single episode of hypothermia of moderate degree in rats, both immediately after cessation of cooling, and in different periods of posthypothermia. Methods. The study was performed on 25 Wistar rats. The animals were subjected to a single immersion cooling in water at a temperature of 5 °C until reaching a rectal temperature of 27-30 °C. Analysis of the microvasculature was carried out immediately upon reaching a moderate degree of hypothermia, 2, 5, 10 and 14 days after the cooling. The microcirculation parameters were estimated using a laser analyzer of capillary circulation LAKK-02 (SMO «Lazma», Russia) at a wavelength of 0.63 μm. The main parameters of microcirculation were recorded, and the amplitude-frequency spectrum of blood flow oscillations was analyzed. Results. Immediately after reaching a moderate degree of hypothermia, vasospasm was recorded, which was confirmed by a decrease in the rate of perfusion and wave amplitudes of all frequency ranges. 2 days after stopping the cooling perfusion index returned to baseline, a decrease in amplitude of endothelial, vasomotor and respiratory waves was observed with an increase in pulse waves. On day 5, perfusion increased by 5 times was observed along with decreased amplitudes of the waves of all ranges. By day 10, the level of blood flow returned to its original values, and the wave amplitudes of all frequency ranges remained at the same low level. By day 14, a progressive decrease of the factors of bloodflow modulation was associated by the decrease of perfusion. Conclusion. Single cooling to a moderate degree of hypothermia leads to a progressive decrease of tissue perfusion and deep inhibition of active and passive factors of bloodflow modulation.