Focus on the brain of the cardiac arrest survivor

Background: Mitochondrial dysfunction contributes to cardiac arrest induced brain injury and has been a target for neuroprotective therapies. An emerging concept suggests that hyperactivation of neuronal mitochondria following resuscitation results in hyperpolarization of the mitochondrial membrane during reperfusion, which drives generation of excess reactive oxygen species. Previous studies from our group demonstrated that limiting mitochondrial hyperactivity by non-invasively modulating mitochondrial function with specific near infrared light (NIR) wavelengths can reduce brain injury in small animal models of global and focal ischemia. Hypothesis: Inhibitory wavelengths of NIR will reduce neuronal injury and improve neurocognitive outcome in a clinically relevant swine model of cardiac arrest. Methods: Twenty-eight male and female adult swine were enrolled (3 groups: Sham, CA/CPR, and CA/CPR + NIR). Cardiac arrest (8 minutes) was induced with a ventricular pacing wire and followed by manual CPR with defibrillation and epinephrine every 30 seconds until return of spontaneous circulation (ROSC), 2 of the 20 swine that underwent CA did not achieve ROSC and were not enrolled. Treatment groups were randomized prior to arrest and blinded to the CPR team. Treatment was applied at onset of ROSC by irradiating the scalp with 750 nm and 950 nm LEDs (5W) for 2 hours. Results: Sham-operated animals all survived (8/8), whereas 22% of untreated animals subjected to cardiac arrest died within 45 min of ROSC (CA/CPR, n= 7/9). All swine treated with NIR survived the duration of the study (CA/CPR + NIR, n=9/9). Four days following cardiac arrest, neurological deficit score was improved in the NIR treatment group (50 ± 21 CA/CPR vs. 0.8 ± 0.8 CA/CPR + NIR, p < 0.05). Additionally, neuronal death in the CA1/CA3 regions of the hippocampus, assessed by counting surviving neurons with stereology, was attenuated by treatment with NIR (17917 ± 5534 neurons/mm 3 CA/CPR vs. 44655 ± 5637 neurons/mm 3 CA/CPR + NIR, p < 0.05). All data is reported as mean ± SEM. Conclusions: These data provide evidence that noninvasive modulation of mitochondria, achieved by transcranial irradiation of the brain with NIR, mitigates post-cardiac arrest brain injury.

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Neuroprognostication of Cardiac Arrest Patients: Outcomes of Importance

Seminars in Respiratory and Critical Care Medicine ◽

10.1055/s-0037-1607988 ◽

2017 ◽

Vol 38 (06) ◽

pp. 775-784

Author(s):

Tobias Cronberg

Keyword(s):

Cardiac Arrest ◽

Vegetative State ◽

Survival Rates ◽

High Quality ◽

Cognitive Difficulties ◽

Cardiac Arrest Survivor ◽

Chain Of Survival ◽

Quality Decision ◽

Improved Methods

AbstractDuring the last two decades, survival rates after cardiac arrest have increased while the fraction of patients surviving with a severe neurological disability or vegetative state has decreased in many countries. While improved survival is due to improvements in the whole “chain of survival,” improved methods for prognostication of neurological outcome may be of major importance for the lower disability rates. Patients who are resuscitated and treated in intensive care will die mainly from the withdrawal of life-sustaining (WLST) therapy due to presumed poor chances of meaningful neurological recovery. To ensure high-quality decision-making and to reduce the risk of premature withdrawal of care, implementation of local protocols is crucial and should be guided by international recommendations. Despite rigorous neurological prognostication, cognitive impairment and related psychological distress and reduced participation in society will still be relevant concerns for cardiac arrest survivors. The commonly used outcome measures are not designed to provide information on these domains. Follow-up of the cardiac arrest survivor needs to consider the cardiovascular burden as an important factor to prevent cognitive difficulties and future decline.

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Glibenclamide Prevents Water Diffusion Abnormality in the Brain After Cardiac Arrest in Rats

Neurocritical Care ◽

10.1007/s12028-018-0505-0 ◽

2018 ◽

Vol 29 (1) ◽

pp. 128-135 ◽

Cited By ~ 8

Author(s):

Kaibin Huang ◽

Ziyue Wang ◽

Yong Gu ◽

Zhong Ji ◽

Zhenzhou Lin ◽

...

Keyword(s):

Cardiac Arrest ◽

Water Diffusion ◽

The Brain

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Abstract P790: Landiolol Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest in Mice

Stroke ◽

10.1161/str.52.suppl_1.p790 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Tomoyuki Iwai ◽

Shin Nakayama

Keyword(s):

Cardiac Arrest ◽

Water Content ◽

Cerebral Edema ◽

Ischemia Reperfusion ◽

Control Group ◽

P Value ◽

Brain Water Content ◽

Arterial Blood ◽

The Brain ◽

Brain Water

Introduction: Cerebral edema following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) is associated with unfavorable neurologic outcome. The Na + -K + -2Cl - water cotransporter NKCC1 is suspected to be a critical mediator of edema formation after ischemia. It is reported that β1 adrenoreceptor antagonists protect neurons following brain ischemia in rodents. β1 adrenoreceptor antagonists inhibit the Na + -K + -ATPase, which can inhibit driving force of NKCC1 that theoretically reduces cerebral edema following ischemia-reperfusion injury. In this study, we examined whether landiolol, a selective β1 adrenoreceptor antagonist, attenuates cerebral edema following CA/CPR. Methods: Isoflurane-anesthetized adult male mice (C57BL/6J, 25-30g) were randomized into landiolol group or control group. After 7-min CA followed by CPR, landiolol (0.5ml, 830μg/ml) was administered by continuous infusion intravenously for 4 hours. Animals in control group were given normal saline (0.5ml) in the same manner. Twenty-four hours after CA/CPR, the brain was removed to assess brain water content using wet-to-dry method. The primary outcome was measurement of the brain water content. Heart rate and arterial blood pressure were recorded. Measured parameters were analyzed by one-way ANOVA with post hoc Tukey-Kramer test using SPSS® statistics 25. Differences were considered statistically significant at a P value < 0.05. Results: Brain water contents was increased in control group mice after CA/CPR (n=10) compared with those in sham operated mice (n=5) (79.5±0.85% vs 78.3±0.14%, P=0.003). Compared with control group, landiolol treatment significantly reduced brain water content in mice subjected to CA/CPR (n=12) (78.9±0.51% vs 79.5±0.85%, P=0.04). Conclusion: Landiolol attenuated brain edema following CA/CPR. These results may suggest selective β1-blocker could be alternative treatment for neuroprotection in patients who suffered CA/CPR.

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Post–Cardiac Arrest Syndrome

AACN Advanced Critical Care ◽

10.4037/aacnacc2020535 ◽

2020 ◽

Vol 31 (4) ◽

pp. 383-393

Author(s):

Linda Dalessio

Keyword(s):

Cardiac Arrest ◽

Myocardial Dysfunction ◽

The United States ◽

Spontaneous Circulation ◽

Clinical State ◽

Precipitating Factors ◽

Patient Health ◽

Global Brain ◽

The Brain ◽

Post Cardiac Arrest Syndrome

More than 356 000 out-of-hospital cardiac arrests occur in the United States annually. Complications involving post–cardiac arrest syndrome occur because of ischemic-reperfusion injury to the brain, lungs, heart, and kidneys. Post–cardiac arrest syndrome is a clinical state that involves global brain injury, myocardial dysfunction, macrocirculatory dysfunction, increased vulnerability to infection, and persistent precipitating pathology (ie, the cause of the arrest). The severity of outcomes varies and depends on precipitating factors, patient health before cardiac arrest, duration of time to return of spontaneous circulation, and underlying comorbidities. In this article, the pathophysiology and treatment of post–cardiac arrest syndrome are reviewed and potential novel therapies are described.

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Evidence for Time-dependent Maximum Increase of Free Radical Damage and Eicosanoid Formation in the Brain as Related to Duration of Cardiac Arrest and Cardio-pulmonary Resuscitation

Free Radical Research ◽

10.1080/1071576021000043058 ◽

2003 ◽

Vol 37 (3) ◽

pp. 251-256 ◽

Cited By ~ 34

Author(s):

Samar Basu ◽

Xiaoli Liu ◽

Ala Nozari ◽

Sten Rubertsson ◽

Adriana Miclescu ◽

...

Keyword(s):

Cardiac Arrest ◽

Free Radical ◽

Time Dependent ◽

Maximum Increase ◽

Free Radical Damage ◽

Cardio Pulmonary Resuscitation ◽

The Brain ◽

Radical Damage ◽

Eicosanoid Formation

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A Case of Dysmnesic Syndrome Following Cardiac Arrest

The British Journal of Psychiatry ◽

10.1192/bjp.111.477.697 ◽

1965 ◽

Vol 111 (477) ◽

pp. 697-699 ◽

Cited By ~ 10

Author(s):

D. L. McNeill ◽

D. Tidmarsh ◽

M. L. Rastall

Keyword(s):

Cardiac Arrest ◽

Geriatric Patients ◽

Occipital Cortex ◽

Psychiatric Disabilities ◽

Pathological Changes ◽

Review Of The Literature ◽

Inferior Colliculi ◽

The Brain ◽

Diagnostic Pitfalls ◽

Circulatory Disturbances

Neuropsychiatric sequelae after cardiac arrest or anaesthesia are infrequently reported. A review of the literature is given by Blackwood et al. (1963). Fletcher (1945) described permanent but comparatively mild effects which were attributed to nitrous oxide rather than to circulatory disturbances. Bedford (1955) described 18 cases of extreme dementia following general anaesthesia in geriatric patients who were quite well mentally before their operations. He indicated the diagnostic pitfalls involved in attributing minor psychiatric disabilities to the anaesthetic. Neuburger (1954) described diffuse cerebral damage combined with Wernicke-like lesions in the mamillary bodies in 2 patients. Brierley (1961) described the pathological changes in the brain of a 2-year-old child, who died 1 month after a cardiac arrest of 10–15 minutes. There were lesions in the mamillary bodies and inferior colliculi resembling those seen in Wernicke's encephalopathy. However, Brierley and Cooper (1962) later described a 43-year-old woman, whose blood pressure fell to unrecordable levels for 3 minutes and who became severely demented, developed Parkinsonism and had a Korsakoff type learning defect. She survived for 23 months. The brain showed most damage in the occipital cortex and thalamus, and less in the midbrain. Unfortunately the mamillary bodies were not identifiable.

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Caseous calcification of the mitral annulus in a cardiac arrest survivor

Revista Portuguesa de Cardiologia ◽

10.1016/j.repc.2019.09.012 ◽

2020 ◽

Vol 39 (5) ◽

pp. 295-297

Author(s):

Alzira Nunes ◽

Paulo Araújo ◽

Sofia Torres ◽

Carla Sousa ◽

Mariana Vasconcelos ◽

...

Keyword(s):

Cardiac Arrest ◽

Mitral Annulus ◽

Cardiac Arrest Survivor

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The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/7463407 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 11

Author(s):

Junhwan Kim ◽

José Paul Perales Villarroel ◽

Wei Zhang ◽

Tai Yin ◽

Koichiro Shinozaki ◽

...

Keyword(s):

Cardiac Arrest ◽

Mitochondrial Respiration ◽

Ischemia Reperfusion ◽

Liver Mitochondria ◽

Brain Mitochondria ◽

Heart Mitochondria ◽

Whole Body ◽

Sprague Dawley ◽

Respiration Activity ◽

The Brain

Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

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