neurosurgeryНейрохирургияRussian journal of neurosurgery1683-32952587-7569Издательский дом "МедИНК"10.63769/1683-3295-2016-0-4-63-72neurosurgery-375Research ArticleОРИГИНАЛЬНАЯ РАБОТАORIGINAL REPORTПРОФИЛАКТИКА ЦЕРЕБРАЛЬНОГО СОСУДИСТОГО СПАЗМА ПРИ СУБАРАХНОИДАЛЬНЫХ КРОВОИЗЛИЯНИЯХ В ЭКСПЕРИМЕНТЕ У КРЫС С ИСПОЛЬЗОВАНИЕМ ФИБРИНОЛИТИЧЕСКИХ ПРЕПАРАТОВThe prophylaxis of cerebral angiospasm developing because of subarachnoid hemorrhage in experiments at rats using fibrinolytic drugsПриродовА. В.PrirodovA. V.noemail@neicon.ruТитоваГ. П.TitovaG. P.noemail@neicon.ruДыдыкинС. С.DydykinS. S.noemail@neicon.ruМаркинС. С.MarkinS. S.noemail@neicon.ruБахаревЕ. Ю.BakharevE. Yu.noemail@neicon.ruКочетковаО. О.KochetkovaO. O.noemail@neicon.ruУсовИ. А.UsovI. A.noemail@neicon.ruКрыловВ. В.KrylovV. V.noemail@neicon.ruНИИ скорой помощи им. Н.В. СклифосовскогоRussian FederationПервый Московский государственный медицинский университет им. И.М. СеченоваRussian FederationНИИ скорой помощи им. Н.В. Склифосовского; Московский государственный медико-стоматологический университет им. А.И. ЕвдокимоваRussian Federation201624112017046372Copyright © Природов А.В., Титова Г.П., Дыдыкин С.С., Маркин С.С., Бахарев Е.Ю., Кочеткова О.О., Усов И.А., Крылов В.В., 20172017Природов А.В., Титова Г.П., Дыдыкин С.С., Маркин С.С., Бахарев Е.Ю., Кочеткова О.О., Усов И.А., Крылов В.В.Prirodov A.V., Titova G.P., Dydykin S.S., Markin S.S., Bakharev E.Y., Kochetkova O.O., Usov I.A., Krylov V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.therjn.com/jour/article/view/375

Цель. Оценить эффективность и безопасность применения фибринолитиков (рекомбинантная стафилокиназа, рекомбинантный человеческий тканевой активатор плазминогена) для профилактики сосудистого спазма (СС) на крысиной модели. Материалы и методы. Эксперимент проведен на 81 белой крысе. Для моделирования СС использовали методику двукратного введения крови в затылочную цистерну крысы. Животные были разделены на 4 группы: 25 особям осуществляли интратекальное введение фортеплазе (рекомбинантная стафилокиназа); 15 особям осуществляли интратекальное введение альтеплазы (рекомбинантный человеческий тканевой активатор плазминогена), 30 особей, которым осуществляли только дренирование ЦСЖ, составили контрольную группу, 11 животным выполняли установку микрокатетера в затылочную цистерну животного (из дальнейшего анализа группа была исключена в связи с неэффективностью санации ЦСЖ). Морфологическое исследование интракраниальных сосудов (верхняя треть базилярной артерии) и вещества головного мозга на уровне среза проводили на 5-е сутки эксперимента с использованием специализированных гистохимических реакций. Результаты. На основании проделанной работы была предложена шкала морфологической оценки СС базилярной артерии крысы, выявлены признаки микроциркуляторных нарушений, характерных для СС. В основной морфологический анализ вошли 25 животных (9 из 1-й группы, 4 из 2-й группы, 12 из 3-й группы). В контрольной группе развитие выраженного СС было отмечено в 4 (33,3%) наблюдениях, умеренного - в 6 (50%), слабого - в 2 (16,7%). В группах с интратекальным введением фибринолитиков выраженного СС не наблюдали. Среди животных, которым вводили фортеплазе, умеренный спазм отмечен у 6 (66,7%) и слабый у 3 (33,3%) животных. У особей, получавших альтеплазу, умеренный и слабый спазм встречался с одинаковой частотой. Формирования внутричерепных геморрагических осложнений отмечено не было. Заключение. Интратекальное введение фибринолитиков является эффективной и безопасной методикой, снижающей выраженность СС на модели двукратного введения крови в затылочную цистерну крысы.

Introduction. The Blood and its degradation products are considered to be the main cause of cerebral angiospasm (CA) due to non-traumatic subarachnoid haemorrhage (SAH). Intrathecal fibrinolytic therapy is one of the most effective methods for clearing the basal cisterns from the blood. Objective. To study the effectiveness and safety of intrathecal fibrinolytic therapy (recombinant staphylokinase, recombinant human plasminogen activator) for CA prevention using double haemorrhage model. Materials and methods. The study was performed on 81 laboratory white rat. The double haemorrhage model was used for reproduction of CA. All animals were divided into 4 groups: 25 were treated with recombinant staphylokinase (fortepase) - group 1, 15 were treated with recombinant tissue plasminogen activator (alteplase) - group 2, 30 animals were included in control group (cerebrospinal fluid drainage only) - group 3, cisternal microcatheter was introduced to 11 animals (group was excluded from further analysis because of CSF drainage inefficiency). Rat brain for morphological study was taken at 5th day. Microscopy assessment was done at the level of the upper third of the basilar artery using special histochemical stains. Results. The morphological scale of CA severity was performed and the specific microcirculatory changes of brain tissues were identified. We included 25 animals (nine from group 1, four from group 2, twelve from group 3) in the main morphological analysis. Mild CA was observed in 4 cases (33,3%), moderate - in six cases (50%), severe - in 4 cases (33,3%) among animals of control group. Severe CA was absent in fibrinolytic groups. Moderate CA was observed in 6 cases (66,7%), mild - in 3 cases (33,3%) in forteplase group. Both mild and moderate CA was observed in 50% of cases in alteplase group. Intracranial haemorrhage was not observed in any group. Conclusion. The proposed intrathecal fibrinolytic therapy is effective and safe method to reduce the severity of CA in rat double haemorrhage model.

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The authors declare that there are no conflicts of interest present.