No abstract

In a rat model of 6-minute ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation or extracorporeal cardiopulmonary resuscitation leads to survival with intact neurologic outcomes. Twelve hours of mild hypothermia attenuated neuronal death in subiculum and thalamus but not CA1 and, surprisingly, increased the microglial response. Resuscitation from ventricular fibrillation cardiac arrest and rigorous temperature control with extracorporeal cardiopulmonary resuscitation in a rat model is feasible, regionally neuroprotective, and alters neuroinflammation versus standard resuscitation. The use of experimental extracorporeal cardiopulmonary resuscitation should be explored using longer insult durations.

Cardiac arrest (CA) triggers neuroinflammation that could play a role in a delayed neuronal death. In our previously established rat model of ventricular fibrillation (VF) CA characterized by extensive neuronal death, we tested the hypothesis that individual brain regions have specific neuroinflammatory responses, as reflected by regional brain tissue levels of tumor necrosis factor (TNF)α and other cytokines. In a prospective study, rats were randomized to 6 min (CA6), 8 min (CA8) or 10 min (CA10) of VF CA, or sham group. Cortex, striatum, hippocampus and cerebellum were evaluated for TNFα and interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12 and interferon gamma at 3 h, 6 h or 14 d after CA by ELISA and Luminex. Immunohistochemistry was used to determine the cell source of TNFα. CA resulted in a selective TNFα response with significant regional and temporal differences. At 3 h after CA, TNFα-levels increased in all regions depending on the duration of the insult. The most pronounced increase was observed in striatum that showed 20-fold increase in CA10 vs. sham, and 3-fold increase vs. CA6 or CA8 group, respectively (p < 0.01). TNFα levels in striatum decreased between 3 h and 6 h, but increased in other regions between 3 h and 14 d. TNFα levels remained twofold higher in CA6 vs. shams across brain regions at 14 d (p < 0.01). In contrast to pronounced TNFα response, other cytokines showed only a minimal increase in CA6 and CA8 groups vs. sham in all brain regions with the exception that IL-1β increased twofold in cerebellum and striatum (p < 0.01). TNFα colocalized with neurons. In conclusion, CA produced a duration-dependent acute TNFα response, with dramatic increase in the striatum where TNFα colocalized with neurons. Increased TNFα levels persist for at least two weeks. This TNFα surge contrasts the lack of an acute increase in other cytokines in brain after CA. Given that striatum is a selectively vulnerable brain region, our data suggest possible role of neuronal TNFα in striatum after CA and identify therapeutic targets for future experiments.

We found that the use of a laryngeal tube for airway management in cardiac arrest was significantly associated with poor 30-day survival rates and unfavourable neurological outcome. A primary endotracheal airway management needs to be considered at the scene, or an earliest possible secondary endotracheal intubation during both pre-hospital and in-hospital post-return of spontaneous circulation critical care seems crucial and most beneficial for the patient outcome.

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 ± 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.