Liver protects neuron viability and electrocortical activity in post-cardiac arrest brain injury
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ABSTRACT:
SUBMITTER: Prof. Zhiyong Guo
PROVIDER: S-SCDT-10_1038-S44321-024-00140-Z | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:[Figure: see text].
| S-EPMC8376277 | biostudies-literature
Project description:Cardiac arrest is a leading cause of death and disability worldwide. Although many victims are initially resuscitated, they often suffer from serious brain injury, even leading to a "persistent vegetative state". Therefore, it is need to explore therapies which restore and protect brain function after cardiac arrest. In the present study, using Tg (HuC:GCaMP5) zebrafish as a model, we found the zebrafish brain generated a burst of Ca2+ wave after cardiac arrest by in vivo time-lapse confocal imaging. The Ca2+ wave was firstly initiated at hindbrain and then sequentially propagated to midbrain and telencephalon, the neuron displayed Ca2+ overload after Ca2+ wave propagation. Consistent with this, our study further demonstrated neuronal apoptosis was increased in cardiac arrest zebrafish by TUNEL staining. The cardiac arrest-induced Ca2+ wave propagation can be prevented by general anesthetics such as midazolam or ketamine pretreatment. Moreover, midazolam or ketamine pretreatment dramatically decreased the neuronal apoptosis and improved the survival rate in CA zebrafish. Taken together, these findings provide the first in vivo evidence that general anesthetics pretreatment protects against cardiac arrest-induced brain injury by inhibiting calcium wave propagation in zebrafish.
| S-EPMC5583756 | biostudies-literature
Project description:IntroductionTrials may be neutral when they do not appropriately target the experimental intervention. We speculated multimodality assessment of early hypoxic-ischemic brain injury would identify phenotypes likely to benefit from therapeutic interventions.MethodsWe performed a retrospective study including comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA) by one of 126 emergency medical services or in-hospital arrest at one of 26 hospitals from 2011 to 2019. All patients were ultimately transported to a single tertiary center for care including standardized initial neurological examination, brain imaging and electroencephalography; targeted temperature management (TTM); hemodynamic optimization targeting mean arterial pressure (MAP) >80 mmHg; and, coronary angiography for clinical suspicion for acute coronary syndrome. We used unsupervised learning to identify brain injury phenotypes defined by admission neurodiagnostics. We tested for interactions between phenotype and TTM, hemodynamic management and cardiac catheterization in models predicting recovery.ResultsWe included 1086 patients with mean (SD) age 58 (17) years of whom 955 (88%) were resuscitated from OHCA. Survival to hospital discharge was 27%, and 248 (23%) were discharged with Cerebral Performance Category (CPC) 1-3. We identified 5 clusters defining distinct brain injury phenotypes, each comprising 14% to 30% of the cohort with discharge CPC 1-3 in 59% to <1%. We found significant interactions between cluster and TTM strategy (P = 0.01), MAP (P < 0.001) and coronary angiography (P = 0.04) in models predicting outcomes.ConclusionsWe identified patterns of early hypoxic-ischemic injury based on multiple diagnostic modalities that predict responsiveness to several therapeutic interventions recently tested in neutral clinical trials.
| S-EPMC7390683 | biostudies-literature
Project description:Post-cardiac arrest brain injury (PCABI) is caused by initial ischaemia and subsequent reperfusion of the brain following resuscitation. In those who are admitted to intensive care unit after cardiac arrest, PCABI manifests as coma, and is the main cause of mortality and long-term disability. This review describes the mechanisms of PCABI, its treatment options, its outcomes, and the suggested strategies for outcome prediction.
| S-EPMC8548866 | biostudies-literature
Project description:BackgroundImpaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury.MethodsA post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TOx) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TOx > 0 indicating impaired reactivity and TOx > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TOx was analysed in the 0-12, 12-24, 24-48 h time-periods and integrated over 0-48 h. The primary outcome was the association between TOx and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3-5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury.ResultsIn 108 patients with sufficient data to calculate TOx, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TOx for 0-48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [- 1.17 to 2.94] vs. - 2.71 95% CI [- 4.16 to - 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15-650] vs 20 IQR [13-199] pg/ml, p = 0.042).ConclusionImpaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL. Trial registration ClinicalTrials.gov, NCT02698917 .
| S-EPMC8477475 | biostudies-literature
Project description:Prophylactic pharmacotherapy for health care in patients with high risk of cardiac arrest (CA) is an elusive and less explored strategy. Melatonin has possibilities used as a daily nutraceutical to trigger the cellular adaptation. We sought to find the effects of long-term daily prophylactic supplement with melatonin on the victim of CA. Rats were divided into sham, CA, and melatonin + CA (Mel + CA) groups. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 min asphyxia and followed by manual cardiopulmonary resuscitation. The endpoint was 24 h after resuscitation. Survival, neurological outcome, and hippocampal mitochondrial integrity, dynamics and function were assessed. Survival was significantly higher in the Mel + CA group than the CA group (81 vs. 42%, P = 0.04). Compared to the CA group, neurological damage in the CA1 region and the level of cytochrome c, cleaved caspase-3 and caspase-9 in the Mel + CA group were decreased (P < 0.05). Mitochondrial function and integrity were protected in the Mel + CA group compared to the CA group, according to the results of mitochondrial swelling, ΔΨm, ROS production, oxygen consumption rate, and respiratory control rate (P < 0.05). Melatonin increased SIRT3 and downregulated acetylated CypD. The mitochondrial dynamics and autophagy were improved in the Mel + CA group (P < 0.05). Long-term daily prophylactic supplement with melatonin buy the time from brain injury after CA.
| S-EPMC10654502 | biostudies-literature
Project description:Few data are available regarding hypoxic hepatitis (HH) and acute liver failure (ALF) in patients resuscitated from cardiac arrest (CA). The aim of this study was to describe the occurrence of these complications and their association with outcome. All adult patients admitted to the Department of Intensive Care following CA were considered for inclusion in this retrospective study. Exclusion criteria were early death (<24 hours) or missing biological data. We retrieved data concerning CA characteristics and markers of liver function. ALF was defined as a bilirubin >1.2 mg/dL and an international normalized ratio ?1.5. HH was defined as an aminotransferase level >1000 IU/L. Neurological outcome was assessed at 3 months and an unfavourable neurological outcome was defined as a Cerebral Performance Categories (CPC) score of 3-5. A total of 374 patients (age 62 [52-74] years; 242 male) were included. ALF developed in 208 patients (56%) and HH in 27 (7%); 24 patients developed both conditions. Patients with HH had higher mortality (89% vs. 51% vs. 45%, respectively) and greater rates of unfavourable neurological outcome (93% vs. 60% vs. 59%, respectively) compared to those with ALF without HH (n = 184) and those without ALF or HH (n = 163; p = 0.03). Unwitnessed arrest, non-shockable initial rhythm, lack of bystander cardiopulmonary resuscitation, high adrenaline doses and the development of acute kidney injury were independent predictors of unfavourable neurological outcome; HH (OR: 16.276 [95% CIs: 2.625-81.345; p = 0.003), but not ALF, was also a significant risk-factor for unfavourable outcome. Although ALF occurs frequently after CA, HH is a rare complication. Only HH is significantly associated with poor neurological outcome in this setting.
| S-EPMC6218055 | biostudies-literature
Project description:BackgroundStandardization of post-cardiac arrest care between emergency department arrival and intensive care unit admission can be challenging, particularly for rural centers, which can experience significant delays in interfacility transfer. One approach to addressing this issue is to form a post-cardiac arrest learning community (P-CALC) consisting of emergency department (ED) and intensive care unit (ICU) physicians and nurses who use data, shared resources, and collaboration to improve post-cardiac arrest care. MaineHealth, the largest regional health system in Maine, launched its P-CALC in 2022.ObjectiveTo explore P-CALC participants' perspectives on current post-cardiac arrest care, attitudes toward implementing a P-CALC intervention, perceived barriers and facilitators to intervention implementation, and implementation strategies.MethodsWe conducted semi-structured, individual, qualitative interviews with 16 staff from seven system EDs spanning the rural-urban spectrum. Directed content analysis was used to discern key themes in transcribed interviews.ResultsParticipants highlighted site- and system-level factors influencing current post-cardiac arrest care. They expressed both positive attitudes and concerns about the P-CALC intervention. Multiple facilitators and barriers were identified in regard to the intervention implementation. Five proposed implementation strategies emerged as important factors to move the intervention forward.ConclusionsImplementation of a P-CALC intervention to effect system-wide improvements in post-cardiac arrest care is complex. Understanding providers' perspectives on current care practices, feasibility of quality improvement, and potential intervention impacts is essential for program development.
| S-EPMC10652430 | biostudies-literature
Project description:Bedside detection and early treatment of lasting cerebral ischemia may improve outcome after out-of-hospital cardiac arrest (OHCA). This feasibility study explores the possibilities to use microdialysis (MD) for continuous monitoring of cerebral energy metabolism by analyzing the draining cerebral venous blood. Eighteen comatose patients were continuously monitored with jugular bulb and radial artery (reference) MD following resuscitation. Median time from cardiac arrest to MD was 300 min (IQR 230-390) with median monitoring time 60 h (IQR 40-81). The lactate/pyruvate ratio in cerebral venous blood was increased during the first 20 h after OHCA, and significant differences in time-averaged mean MD metabolites between jugular venous and artery measurements, were documented (p < 0.02). In patients with unfavorable outcome (72%), cerebral venous lactate and pyruvate levels remained elevated during the study period. In conclusion, the study indicates that jugular bulb microdialysis (JBM) is feasible and safe. Biochemical signs of lasting ischemia and mitochondrial dysfunction are frequent and associated with unfavorable outcome. The technique may be used in comatose OHCA patients to monitor biochemical variables reflecting ongoing brain damage and support individualized treatment early after resuscitation.
| S-EPMC8342553 | biostudies-literature
Project description:ObjectiveTo determine the association between the extent of diffusion restriction and T2/fluid-attenuated inversion recovery (FLAIR) injury on brain MRI and outcomes after pediatric out-of-hospital cardiac arrest (OHCA).MethodsDiffusion restriction and T2/FLAIR injury were described according to the pediatric MRI modification of the Alberta Stroke Program Early Computed Tomography Score (modsASPECTS) for children from 2005 to 2013 who had an MRI within 14 days of OHCA. The primary outcome was unfavorable neurologic outcome defined as ≥1 change in Pediatric Cerebral Performance Category (PCPC) from baseline resulting in a hospital discharge PCPC score 3, 4, 5, or 6. Patients with unfavorable outcomes were further categorized into alive with PCPC 3-5, dead due to withdrawal of life-sustaining therapies for poor neurologic prognosis (WLST-neuro), or dead by neurologic criteria.ResultsWe evaluated MRI scans from 77 patients (median age 2.21 [interquartile range 0.44, 13.07] years) performed 4 (2, 6) days postarrest. Patients with unfavorable outcomes had more extensive diffusion restriction (median 7 [4, 10.3] vs 0 [0, 0] regions, p < 0.001) and T2/FLAIR injury (5.5 [2.3, 8.2] vs 0 [0, 0.75] regions, p < 0.001) compared to patients with favorable outcomes. Area under the receiver operating characteristic curve for the extent of diffusion restriction and unfavorable outcome was 0.96 (95% confidence interval [CI] 0.91, 0.99) and 0.92 (95% CI 0.85, 0.97) for T2/FLAIR injury. There was no difference in extent of diffusion restriction between patients who were alive with an unfavorable outcome and patients who died from WLST-neuro (p = 0.11).ConclusionsMore extensive diffusion restriction and T2/FLAIR injury on the modsASPECTS score within the first 14 days after pediatric cardiac arrest was associated with unfavorable outcomes at hospital discharge.
| S-EPMC7884994 | biostudies-literature