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The prophylaxis of cerebral angiospasm developing because of subarachnoid hemorrhage in experiments at rats using fibrinolytic drugs

Abstract

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.

About the Authors

A. V. Prirodov
НИИ скорой помощи им. Н.В. Склифосовского
Russian Federation


G. P. Titova
НИИ скорой помощи им. Н.В. Склифосовского
Russian Federation


S. S. Dydykin
Первый Московский государственный медицинский университет им. И.М. Сеченова
Russian Federation


S. S. Markin
Первый Московский государственный медицинский университет им. И.М. Сеченова
Russian Federation


E. Yu. Bakharev
НИИ скорой помощи им. Н.В. Склифосовского
Russian Federation


O. O. Kochetkova
НИИ скорой помощи им. Н.В. Склифосовского
Russian Federation


I. A. Usov
Первый Московский государственный медицинский университет им. И.М. Сеченова
Russian Federation


V. V. Krylov
НИИ скорой помощи им. Н.В. Склифосовского; Московский государственный медико-стоматологический университет им. А.И. Евдокимова
Russian Federation


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Prirodov A.V., Titova G.P., Dydykin S.S., Markin S.S., Bakharev E.Yu., Kochetkova O.O., Usov I.A., Krylov V.V. The prophylaxis of cerebral angiospasm developing because of subarachnoid hemorrhage in experiments at rats using fibrinolytic drugs. Russian journal of neurosurgery. 2016;(4):63-72. (In Russ.)

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