Abstract
Objectives. The aim of the study was to investigate of the effect of administration of Notrombel, (one of the representatives of a new class of compounds, N,N'-substituted piperazines), on systemic hemodynamics and thrombin tolerance. Material and methods. The effect of daily intragastric administration for 14 days of Notrombel (0.01 mM/kg) and ASA (0.01 mM/kg) on the risk of spontaneous hemorrhages and thrombin tolerance (intravenous bolus thrombin administration at a dose of 50 units NIH/kg) was studied in male Wistar rats. The number of circulating platelets was determined before and 5 minutes after thrombin administration. The concentration of fibrinogen after 30 min was determined by the gravimetric method according to Rutberg R. A. Results. With the daily intragastric administration of Notrombel and ASA, spontaneous hemorrhages and increased bleeding were not observed. Blood pressure and heart rate did not differ from the control animals. Intravenous administration of thrombin caused thrombocytopenia and hypofibrinogenemia in all experimental animals. The severity of hypofibrinogenemia after thrombin administration was significantly less in rats treated with Notrombel (0.01 mM/kg) and ASA (0.01 mM/kg) than in the control group. There were no differences between Notreblel and ASA groups. Conclusions. Daily intragastric administration of Notrombel and ASA for 14 days did not cause spontaneous hemorrhages and were not associated with any adverse hemodynamic effect. Both Notrombel and ASA increased tolerance to thrombin. These data broaden the currently available knowledge related to the antithrombotic action of Notrombel.
Highlights
The aim of the study was to investigate of the effect of administration of Notrombel, on systemic hemodynamics and thrombin tolerance
The concentration of fibrinogen after 30 min was determined by the gravimetric method according to Rutberg R.A
The severity of hypofibrinogenemia after thrombin administration was significantly less in rats treated with Notrombel (0.01 mM/kg) and ASA (0.01 mM/kg) than in the control group
Summary
Экспериментальные животные стируемых растворов проводили через 20–30 мин Исследования проводились на крысах-самцах ли- после окончания хирургических манипуляций и при нии Вистар (возраст – 15–18 недель, масса – 250–270 г) условии стабильной гемодинамики. В качестве препарата сравнения использовали растворяли содержимое при комнатной температуре ацетилсалициловую кислоту (АСК) (Sigma Aldrich, (+18–25 оС) и легком покачивании в течение 3 мин. Забор крови для водили через 24 ч после 14-го введения препаратов определения концентрации тромбина проводили либо воды. Из правой яремной вены через 30 мин после введения тромбина (стабилизатор – цитрат натрия 3,2 %, Исследование влияния Нотромбела на систем- 1 часть на 9 частей крови). Уд./мин толерантности в процентах: остаточная концентрация фибриногена в плазме крови (в % к исходной) у интактных крыс = 100 %-й толерантности; Контроль (n=5) Нотромбел. Через 5 мин после прекращения дыхательных движений и сердечных сокращений проводили вскрытие и морфологическое исследование макроскопическим методом.
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