Minocycline attenuates microglial response and reduces neuronal death after cardiac arrest and cardiopulmonary resuscitation in mice

The mechanisms leading to delayed neuronal death after asphyxial cardiac arrest (ACA) in the developing brain are unknown. This study aimed at investigating the possible role of microglial activation in neuronal death in developing brain after ACA. Postnatal day-17 rats were subjected to 9 mins of ACA followed by resuscitation. Rats were randomized to treatment with minocycline, (90 mg/kg, intraperitoneally (i.p.)) or vehicle (saline, i.p.) at 1 h after return of spontaneous circulation. Thereafter, minocycline (22.5 mg/kg, i.p.) was administrated every 12 h until sacrifice. Microglial activation (evaluated by immunohistochemistry using ionized calcium-binding adapter molecule-1 (Iba1) antibody) coincided with DNA fragmentation and neurodegeneration in CA1 hippocampus and cortex (assessed by deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL), Fluoro-Jade-B and Nissl stain). Minocycline significantly decreased both the microglial response and neuronal degeneration compared with the vehicle. Asphyxial CA significantly enhanced proinflammatory cytokine and chemokine levels in hippocampus versus control (assessed by multiplex bead array assay), specifically tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1α (MIP-1α), regulated upon activation, normal T-cell expressed and secreted (RANTES), and growth-related oncogene (GRO-KC) ( P<0.05). Minocycline attenuated ACA-induced increases in MIP-1α and RANTES ( P<0.05). These data show that microglial activation and cytokine production are increased in immature brain after ACA. The beneficial effect of minocycline suggests an important role for microglia in selective neuronal death after pediatric ACA, and a possible therapeutic target.

Download Full-text

Inhibition of Soluble Epoxide Hydrolase after Cardiac Arrest/Cardiopulmonary Resuscitation Induces a Neuroprotective Phenotype in Activated Microglia and Improves Neuronal Survival

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.111 ◽

2013 ◽

Vol 33 (10) ◽

pp. 1574-1581 ◽

Cited By ~ 19

Author(s):

Jianming Wang ◽

Tetsuhiro Fujiyoshi ◽

Yasuharu Kosaka ◽

Jonathan D Raybuck ◽

K Matthew Lattal ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Neuronal Death ◽

Epoxide Hydrolase ◽

Memory Function ◽

Specific Treatment ◽

Neuronal Loss ◽

Soluble Epoxide Hydrolase ◽

Activated Microglia ◽

Tnf Α

Cardiac arrest (CA) causes hippocampal neuronal death that frequently leads to severe loss of memory function in survivors. No specific treatment is available to reduce neuronal death and improve functional outcome. The brain's inflammatory response to ischemia can exacerbate injury and provides a potential treatment target. We hypothesized that microglia are activated by CA and contribute to neuronal loss. We used a mouse model to determine whether pharmacologic inhibition of the proinflammatory microglial enzyme soluble epoxide hydrolase (sEH) after CA alters microglial activation and neuronal death. The sEH inhibitor 4-phenylchalcone oxide (4-PCO) was administered after successful cardiopulmonary resuscitation (CPR). The 4-PCO treatment significantly reduced neuronal death and improved memory function after CA/CPR. We found early activation of microglia and increased expression of inflammatory tumor necrosis factor (TNF)-α and interleukin (IL)-1β in the hippocampus after CA/CPR, which was unchanged after 4-PCO treatment, while expression of antiinflammatory IL-10 increased significantly. We conclude that sEH inhibition after CA/CPR can alter the transcription profile in activated microglia to selectively induce antiinflammatory and neuroprotective IL-10 and reduce subsequent neuronal death. Switching microglial gene expression toward a neuroprotective phenotype is a promising new therapeutic approach for ischemic brain injury.

Download Full-text

Normoxic resuscitation after cardiac arrest protects against hippocampal oxidative stress, metabolic failure, and neuronal death

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0042 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S42-S42

Author(s):

Robert E Rosenthal ◽

Viktoria Vereczki ◽

Erica M Martin ◽

Gary Fiskum

Keyword(s):

Oxidative Stress ◽

Cardiac Arrest ◽

Neuronal Death

Download Full-text

Faculty Opinions recommendation of Soluble epoxide hydrolase gene deletion reduces survival after cardiac arrest and cardiopulmonary resuscitation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1097222.553232 ◽

2007 ◽

Author(s):

Deanna Kroetz

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Epoxide Hydrolase ◽

Gene Deletion ◽

Soluble Epoxide Hydrolase

Download Full-text

Impact of cardiopulmonary resuscitation on a cannot intubate, cannot oxygenate condition: a randomised crossover simulation research study of the interaction between two algorithms

BMJ Open ◽

10.1136/bmjopen-2019-030430 ◽

2019 ◽

Vol 9 (11) ◽

pp. e030430

Author(s):

Thomas Ott ◽

Jascha Stracke ◽

Susanna Sellin ◽

Marc Kriege ◽

Gerrit Toenges ◽

...

Keyword(s):

Decision Making ◽

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Primary Outcome ◽

Research Study ◽

University Hospital ◽

Simulated Patients ◽

Stressful Situation ◽

Simulation Research ◽

Simulation Centre

ObjectivesDuring a ‘cannot intubate, cannot oxygenate’ situation, asphyxia can lead to cardiac arrest. In this stressful situation, two complex algorithms facilitate decision-making to save a patient’s life: difficult airway management and cardiopulmonary resuscitation. However, the extent to which competition between the two algorithms causes conflicts in the execution of pivotal treatment remains unknown. Due to the rare incidence of this situation and the very low feasibility of such an evaluation in clinical reality, we decided to perform a randomised crossover simulation research study. We propose that even experienced healthcare providers delay cricothyrotomy, a lifesaving approach, due to concurrent cardiopulmonary resuscitation in a ‘cannot intubate, cannot oxygenate’ situation.DesignDue to the rare incidence and dynamics of such a situation, we conducted a randomised crossover simulation research study.SettingWe collected data in our institutional simulation centre between November 2016 and November 2017.ParticipantsWe included 40 experienced staff anaesthesiologists at our tertiary university hospital centre.InterventionThe participants treated two simulated patients, both requiring cricothyrotomy: one patient required cardiopulmonary resuscitation due to asphyxia, and one patient did not require cardiopulmonary resuscitation. Cardiopulmonary resuscitation was the intervention. Participants were evaluated by video records.Primary outcome measuresThe difference in ‘time to ventilation through cricothyrotomy’ between the two situations was the primary outcome measure.ResultsThe results of 40 participants were analysed. No carry-over effects were detected in the crossover design. During cardiopulmonary resuscitation, the median time to ventilation was 22 s (IQR 3–40.5) longer than that without cardiopulmonary resuscitation (p=0.028), including the decision-making time.ConclusionCricothyrotomy, which is the most crucial treatment for cardiac arrest in a ‘cannot intubate, cannot oxygenate’ situation, was delayed by concurrent cardiopulmonary resuscitation. If cardiopulmonary resuscitation delays cricothyrotomy, it should be interrupted to first focus on cricothyrotomy.

Download Full-text

Management of out-of hospital cardiac arrest patients with extracorporeal cardiopulmonary resuscitation in 2021

Expert Review of Medical Devices ◽

10.1080/17434440.2021.1886076 ◽

2021 ◽

pp. 1-10

Author(s):

Christopher Gaisendrees ◽

Matias Vollmer ◽

Sebastian G Walter ◽

Ilija Djordjevic ◽

Kaveh Eghbalzadeh ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Extracorporeal Cardiopulmonary Resuscitation ◽

Hospital Cardiac Arrest

Download Full-text

How long should we run the code? Survival analysis based on location and duration of cardiopulmonary resuscitation (CPR) after in-hospital cardiac arrest

Journal of Community Hospital Internal Medicine Perspectives ◽

10.1080/20009666.2021.1877396 ◽

2021 ◽

Vol 11 (2) ◽

pp. 206-211

Author(s):

Ahmad Raza ◽

Ahmad Arslan ◽

Zain Ali ◽

Rajeshkumar Patel

Keyword(s):

Cardiac Arrest ◽

Survival Analysis ◽

Cardiopulmonary Resuscitation ◽

Hospital Cardiac Arrest

Download Full-text

Cardiac arrest complicating cardiogenic shock: from pathophysiological insights to Impella-assisted cardiopulmonary resuscitation in a pheochromocytoma-induced Takotsubo cardiomyopathy—a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytab092 ◽

2021 ◽

Vol 5 (3) ◽

Author(s):

Filippo Zilio ◽

Simone Muraglia ◽

Roberto Bonmassari

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Left Ventricle ◽

Cardiogenic Shock ◽

Takotsubo Cardiomyopathy ◽

Perfusion Pressure ◽

Coronary Perfusion Pressure ◽

Left Ventricular ◽

Coronary Perfusion ◽

Refractory Cardiac Arrest

Abstract Background A ‘catecholamine storm’ in a case of pheochromocytoma can lead to a transient left ventricular dysfunction similar to Takotsubo cardiomyopathy. A cardiogenic shock can thus develop, with high left ventricular end-diastolic pressure and a reduction in coronary perfusion pressure. This scenario can ultimately lead to a cardiac arrest, in which unloading the left ventricle with a peripheral left ventricular assist device (Impella®) could help in achieving the return of spontaneous circulation (ROSC). Case summary A patient affected by Takotsubo cardiomyopathy caused by a pheochromocytoma presented with cardiogenic shock that finally evolved into refractory cardiac arrest. Cardiopulmonary resuscitation was performed but ROSC was achieved only after Impella® placement. Discussion In the clinical scenario of Takotsubo cardiomyopathy due to pheochromocytoma, when cardiogenic shock develops treatment is difficult because exogenous catecholamines, required to maintain organ perfusion, could exacerbate hypertension and deteriorate the cardiomyopathy. Moreover, as the coronary perfusion pressure is critically reduced, refractory cardiac arrest could develop. Although veno-arterial extra-corporeal membrane oxygenation (va-ECMO) has been advocated as the treatment of choice for in-hospital refractory cardiac arrest, in the presence of left ventricular overload a device like Impella®, which carries fewer complications as compared to ECMO, could be effective in obtaining the ROSC by unloading the left ventricle.

Download Full-text

Does Targeted Temperature Management Improve Neurological Outcome in Extracorporeal Cardiopulmonary Resuscitation (ECPR)?

Journal of Intensive Care Medicine ◽

10.1177/08850666211018982 ◽

2021 ◽

pp. 088506662110189

Author(s):

Merry Huang ◽

Aaron Shoskes ◽

Migdady Ibrahim ◽

Moein Amin ◽

Leen Hasan ◽

...

Keyword(s):

Cardiac Arrest ◽

Cardiopulmonary Resuscitation ◽

Neurological Outcome ◽

Targeted Temperature Management ◽

Temperature Management ◽

Survival Outcomes ◽

Pool Data ◽

Good Neurological Outcome ◽

Extracorporeal Cardiopulmonary Resuscitation ◽

Over Time

Purpose: Targeted temperature management (TTM) is a standard of care in patients after cardiac arrest for neuroprotection. Currently, the effectiveness and efficacy of TTM after extracorporeal cardiopulmonary resuscitation (ECPR) is unknown. We aimed to compare neurological and survival outcomes between TTM vs non-TTM in patients undergoing ECPR for refractory cardiac arrest. Methods: We searched PubMed and 5 other databases for randomized controlled trials and observational studies reporting neurological outcomes or survival in adult patients undergoing ECPR with or without TTM. Good neurological outcome was defined as cerebral performance category <3. Two independent reviewers extracted the data. Random-effects meta-analyses were used to pool data. Results: We included 35 studies (n = 2,643) with the median age of 56 years (interquartile range [IQR]: 52-59). The median time from collapse to ECMO cannulation was 58 minutes (IQR: 49-82) and the median ECMO duration was 3 days (IQR: 2.0-4.1). Of 2,643, 1,329 (50.3%) patients received TTM and 1,314 (49.7%) did not. There was no difference in the frequency of good neurological outcome at any time between TTM (29%, 95% confidence interval [CI]: 23%-36%) vs. without TTM (19%, 95% CI: 9%-31%) in patients with ECPR ( P = 0.09). Similarly, there was no difference in overall survival between patients with TTM (30%, 95% CI: 22%-39%) vs. without TTM (24%, 95% CI: 14%-34%) ( P = 0.31). A cumulative meta-analysis by publication year showed improved neurological and survival outcomes over time. Conclusions: Among ECPR patients, survival and neurological outcome were not different between those with TTM vs. without TTM. Our study suggests that neurological and survival outcome are improving over time as ECPR therapy is more widely used. Our results were limited by the heterogeneity of included studies and further research with granular temperature data is necessary to assess the benefit and risk of TTM in ECPR population.

Download Full-text