ESTABLISHING A RODENT MODEL OF VENTRICULAR FIBRILLATION CARDIAC ARREST WITH GRADED HISTOLOGIC AND NEUROLOGIC DAMAGE WITH DIFFERENT CARDIAC ARREST DURATIONS

ESTABLISHING A RODENT MODEL OF VENTRICULAR FIBRILLATION CARDIAC ARREST WITH GRADED HISTOLOGIC AND NEUROLOGIC DAMAGE WITH DIFFERENT CARDIAC ARREST DURATIONS
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DOI:
10.1097/shk.0000000000001004
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发表时间:
2018-08-01
期刊:
影响因子:
3.1
通讯作者:
Janata, Andreas
Janata, Andreas
中科院分区:
医学2区
文献类型:
--
作者:
Ettl, Florian;Magnet, Ingrid A. M.;Janata, Andreas

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目的:本研究旨在建立一种以一致的神经和神经病理损伤为潜在治疗靶点的心室颤动(VF)心脏骤停(CA)复苏模型。方法:前瞻性随机分组实验,分两期进行。在第1阶段,4组雄性Sprague-Dawley大鼠(n =5)分别在有和没有肾上腺素的情况下,分别在6分钟VFCA、2分钟和6分钟基本生命维持时间(BLS)后复苏。在第二阶段,将自发循环恢复(ROSC)和生存最有希望的组与8分钟CA组进行比较。每天评估复苏能力、神经功能缺陷评分(NDS)和总体表现类别(OPC);第14天海马CA1区[苏木精和伊红-(活神经元),Fluoro-Jade-(死亡神经元)和Iba-1免疫染色(小胶质细胞激活-半定量)]的组织病理学。结果:2分钟BLS和肾上腺素作为第一阶段最有希望的组,与第二阶段8分钟组相比,8只动物(80%)比9只动物(82%)出现ROSC,存活到第14天的动物中有7只(88%)(所有OPC 1, NDS 0 =)比6只(67%)(5只OPC 1, 1只OPC 2, NDS 0.83 +/- 2.4)。OPC和NDS仅在第1天有显著差异(OPC: P = 0.035; NDS: P = 0.003)。两组间组织病理学结果差异无统计学意义;然而,在8分钟组中发现病变程度的差异较小。总的来说,两种CA的持续时间都引起了神经系统的分级损伤,如组织病理学损伤。结论:该动态全脑缺血模型为进一步评估CA后的认知和新型神经保护治疗试验提供了可能。
Purpose: The aim of the study was to establish a ventricular fibrillation (VF) cardiac arrest (CA) resuscitation model with consistent neurologic and neuropathologic damage as potential therapeutic target. Methods: Prospectively randomized groups of experiments in two phases. In phase 1 four groups of male Sprague-Dawley rats (n =5) were resuscitated after 6 min VFCA with 2 and 6 min basic life support durations (BLS) with and without adrenaline. In phase 2 the most promising group regarding return of spontaneous circulation (ROSC) and survival was compared with a group of 8 min CA. Resuscitability, neurologic deficit scores (NDS), and overall performance category (OPC) were assessed daily; histolopathology of the hippocampal CA1 region [hematoxylin and eosin-(viable neurons), Fluoro-Jade-(dying neurons), and Iba-1 immunostaining (microglial activation-semiquantitative)] on day 14. Results: Two minutes BLS and with adrenaline as most promising group of phase 1 compared with an 8 min group in phase 2 exhibited ROSC in 8 (80%) vs. 9 (82%) animals and survivors till day 14 in 7 (88%) (all OPC 1, NDS 0 = ) vs. 6 (67%) (5 OPC 1, 1 OPC 2, NDS 0.83 +/- 2.4) animals. OPC and NDS were only significantly different at day 1 (OPC: P = 0.035; NDS: P = 0.003). Histopathologic results between groups were not significantly different; however, a smaller variance of extent of lesions was found in the 8 min group. Both CA durations caused graded neurologic, overall, such as histopathologic damage. Conclusions: This dynamic global ischemia model offers the possibility to evaluate further cognitive and novel neuroprotective therapy testing after CA.