<p><strong>Background.</strong> There is a continued search for effective and safe drugs with systemic hemostatic effects. Experimental data from previous studies show that low-dose fibrin monomer (FM) can reduce posttraumatic bleeding without causing activation of clotting in the circulating blood.</p><p><strong>Aim.</strong> To study the systemic hemostatic and hemostasiological effects of prophylactic intravenous administration of FM on the background of fibrinolysis activation by streptokinase.</p><p><strong>Methods.</strong> In a placebo-controlled study using male rabbits, fibrinolysis was activated by intravenous administration of streptokinase at a dose of 150,000 IU/kg. One hour before liver injury, FM was administered intravenously at a dose of 0.25 mg/kg. Tranexamic acid (TXA) was administered intravenously at a dose of 15 mg/kg 30 min before injury as a reference drug. After metered-dose injuring, blood loss was estimated as % of the circulating blood volume and by the rate of blood loss (mg/s). The study of blood platelet count, activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration and the results of rotational blood thromboelastometry were taken into consideration.</p><p><strong>Results.</strong> Administration of FM and TXA before fibrinolysis activation by streptokinase reduced the blood loss volume by 11.0 and 15.4 times, respectively. FM and TXA both reduced the blood loss rate by 3.8 times compared to the placebo group that received the same fibrinolytic. The administration of streptokinase in all cases was accompanied by 23–30% a decrease in the fibrinogen concentration without affecting APTT and TT. The hemostatic effects of FM and TXA were observed in vivo while preserving the density properties of the blood clot (according to the parameters of α angle, MCF and A10 in thromboelastometry) despite the administration of streptokinase, whereas a significant decrease in these parameters was observed in the placebo group.</p><p><strong>Conclusion.</strong> The systemic hemostatic effects of FM at a dose of 0.25 mg/kg with fibrinolysis activation by streptokinase were close to the effects of TXA. Thus, FM administration can be considered a promising hemostatic therapy for the reduction of thrombolysis-associated bleeding.</p><p>Received 18 December 2019. Accepted 22 January 2020.</p><p><strong>Funding:</strong> The study was supported by a grant from the Russian Foundation for Basic Research (No. 18-415-220001), Altai State Medical University.</p><p><strong>Conflict of interest:</strong> Authors declare no conflict of interest.</p><p><strong>Author contributions</strong><br />Conception and study design: A.P. Momot, V.M. Vdovin, I.I. Shakhmatov</p><p>Data collection: V.M. Vdovin, D.A. Orekhov, V.O. Krasyukova, N.A. Lycheva, D.A. Momot, V.E. Chernus, V.V. Terjaev</p><p>Data analysis: A.P. Momot, V.M. Vdovin</p><p>Drafting the article: V.M. Vdovin, A.P. Momot</p><p>Critical revision of the article: A.P. Momot, В V.M. Vdovin</p><p>Statistical analysis: V.M. Vdovin</p><p>Final approval of the version to be published: V.M. Vdovin, A.P. Momot, D.A. Orekhov, V.O. Krasyukova, I.I. Shakhmatov, N.A. Lycheva, D.A. Momot, V.E. Chernus, V.V. Terjaev</p>
The involvement of various associations of bacterial and viral nature in the infectious and pathological processes creates difficul-ties in the early diagnosis of infectiones, including respiratory diseases, that dramati-cally reduces the effectiveness of preventive and therapeutic measures. Therefore, at pre-sent, the most justified way to increase the effectiveness of antiepizootic measures is to find modern disinfectants with a wide spec-trum of antimicrobial activity. The purpose of the work is to conduct assay of the “Fumiyod” drug in the form of fumigation aerosols at the conditions of farms in the Leningrad Region, for the treatment of young cattle and pigs with symptoms of infectious respiratory diseases. The diagno-sis of respiratory diseases, including bron-chopneumonia, infectious rhinotracheitis, rhinitis was set comprehensively in calves aged 5-6 months and repair young pigs aged 4-5 months. Tested samples of iodine-containing checkers (Fumiyod preparation) were sublimated at exposition for 3 hours. According to the literature and the results of previous in-house production tests, iodine vapor at a concentration of about 0.02 g / m3 has a fairly high bactericidal activity. The therapeutic efficacy from the use of the “Fumiyod” drug in the form of fumigation aerosols for calves and repair pigs was about 90%. Recovery of young animals from res-piratory diseases (by the disappearance of symptoms) in the experimental groups after 4 times of use of iodine inhalations of the “Fumiyod” drug (every other day, once a day), within the bactericidal concentration of iodine vapor 0.02 g / m3, with an exposure of 1 hour, occurred 2 days earlier than in the control group with the useof the antibiotic oxytetracycline at a dose of 30-40 thousand units / kg of body weight per day for 10-12 days. The use of iodine checkers did not negatively affect the health status of calves and piglets in the experimental groups, and did not cause complications in animals.
Цель исследования - изучение способности фибрин-мономера предупреждать тяжелую интраоперационную кровопотерю, ассоциированную с введением нефракционированного гепарина, при дозированной травме печени. Методика. На кроликах «Шиншилла» индуцировали гипокоагуляцию нефракционированным гепарином (150 ед/кг). Профилактику интраоперационных кровотечений осуществляли внутривенным введением фибрин-мономера (0,25 мг/кг) за 1 ч до травмы или протамина сульфата (1,5 мг/кг) за 10 мин до травмы. После нанесения стандартной травмы печени оценивали объем (в % ОЦК) и темп (мг/с) кровопотери. Анализировали число тромбоцитов, активированное парциальное тромбопластиновое время, протромбиновое и тромбиновое время свертывания, уровень фибриногена и активность антитромбина III, параметры ротационной тромбоэластометрии крови. Результаты. Объем кровопотери в группах животных после в/в введения фибрин-мономера и протамина сульфата на фоне гепаринизации был, соответственно, в 5,1 и 4,0 раза меньше по сравнению с группой плацебо, получавшей тот же антикоагулянт. Вместе с тем, фибрин-мономер не влиял на параметры коагулограммы (отсутствие видимого гемостазиологического эффекта) и тромбоэластограммы, тогда как применение протамина сульфата в качестве антидота гепарина сопровождалось нормализацией данных тромбоэластометрии и коррекцией гипокоагуляционного сдвига по активированному парциальному тромбопластиновому времени, протромбиновому и тромбиновому времени. Заключение. Установлено, что фибрин-мономер (0,25 мг/кг) снижает посттравматическое кровотечение в условиях блокады свертывания крови гепарином без видимых признаков восстановления гемостатического равновесия. The research objective was to study the ability of fibrin monomer to prevent severe intraoperative blood loss associated with administration of unfractionated heparin in controlled liver injury. Methods. Hypocoagulation was induced in chinchilla rabbits with unfractionated heparin (150 U/kg). Intraoperative bleeding was prevented by administration of fibrin monomer (FM, 0.25 mg/kg, i.v.) one hour prior to the injury and of protamine sulfate (PS, 1.5 mg/kg, i.v.) 10 min prior to the injury. Following the liver injury, blood loss was assessed as percentage of circulating blood volume and the blood loss rate (mg/s). Platelet counts, aPTT, PT, TT, fibrinogen level, antithrombin III activity, and parameters of blood rotation thromboelastometry were analyzed. Results. The volume of blood loss was 5.1 times and 4.0 times less, respectively, after the FM and PS administration during heparinization compared to the placebo group treated with the same anticoagulant. However, FM affected neither coagulogram indexes (no visible hemostasiological effect) nor thromboelastogram while the use of PS as an antidote for heparin was associated with normalization of thromboelastometric data and correction of hypercoagulative changes in aPTT, PT, TT. Conclusion. FM at a dose of 0.25 mg/kg reduced severity of posttraumatic bleeding induced by heparin inhibition of coagulation with no visible signs of hemostatic balance recovery.
The purpose of the work is to study the anti-microbial activity of fumigation aerosols of the Fumiyod preparation using bactericidal blocks against isolates of opportunistic mi-croflora from calves and piglets with signs of infectious respiratory diseases. The work was carried out on livestock and pig farms of Volosovsky district of the Leningrad region. Samples of biomaterial (nasal swabs and nasopharyngeal swabs) were taken from dis-eased animals to determine the sensitivity of the microflora to the studied iodine-containing Fumiyod preparation (experiment) and 1% glutaraldehyde solution (control). The biomaterial was plated on elective nutrient media (milk-yolk-salt agar, blood agar, Endo medium, yolk-salt agar). Cultures of microorganisms (Klebsiella pneumonia, Str.pneumoniae, St. aureus, Pro-teus vulgaris, Pseudomonas aeruginosa, E. coli), yeast were isolated from washouts from the nasal cavity and nasopharyngial washings from calves and piglets with symp-toms of bronchopneumonia, pneumonia, bronchitis, rhinitis albicans) and fungi (Mucor sp., Aspergillus fumigatus). Using paper discs, it was found that the Fumiyod preparation in the form of fumigation aero-sols, used in the form of bactericidal check-ers, has a high bactericidal activity in vitro (microbial growth inhibition zone of more than 15 mm) in relation to all microflora isolates from calves and pigs with signs of respiratory diseases, which manifested by a wide range of antimicrobial and antimycotic effects. The final concentration of the Fumiyod preparation was revealed for the active active substance - 0.20 g / m3, in which a wider spectrum of its antimicrobial (growth suppression zone within 26-32 mm) and antimycotic (growth suppression zone within 27-31 mm ) actions com-pared with 1% glutaraldehyde (control), respective-ly, in the range of 20-25 mm and 21-24 mm.
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