Dataset Information

Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model.

ABSTRACT:

Introduction

Swine exhibit cerebral cortex mitochondrial dysfunction and neuropathologic injury after hypoxic cardiac arrest treated with hemodynamic-directed CPR (HD-CPR) despite normal Cerebral Performance Category scores. We analyzed the temporal evolution of plasma protein biomarkers of brain injury and inflammatory cytokines, as well as cerebral cortical mitochondrial injury and neuropathology for five days following pediatric asphyxia-associated cardiac arrest treated with HD-CPR.

Methods

One-month-old swine underwent asphyxia associated cardiac arrest, 10-20 min of HD-CPR (goal SBP 90 mmHg, coronary perfusion pressure 20 mmHg), and randomization to post-ROSC survival duration (24, 48, 72, 96, 120 h; n = 3 per group) with standardized post-resuscitation care. Plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and cytokine levels were collected pre-injury and 1, 6, 24, 48, 72, 96, and 120 h post-ROSC. Cerebral cortical tissue was assessed for: mitochondrial respirometry, mass, and dynamic proteins; oxidative injury; and neuropathology.

Results

Relative to pre-arrest baseline (9.4 pg/ml [6.7-12.6]), plasma NfL was increased at all post-ROSC time points. Each sequential NfL measurement through 48 h was greater than the previous value {1 h (12.7 pg/ml [8.4-14.6], p = 0.01), 6 h (30.9 pg/ml [17.7-44.0], p = 0.0004), 24 h (59.4 pg/ml [50.8-96.1], p = 0.0003) and 48 h (85.7 pg/ml [61.9-118.7], p = 0.046)}. Plasma GFAP, inflammatory cytokines or cerebral cortical tissue measurements were not demonstrably different between time points.

Conclusions

In a swine model of pediatric cardiac arrest, plasma NfL had an upward trajectory until 48 h post-ROSC after which it remained elevated through five days, suggesting it may be a sensitive marker of neurologic injury following pediatric cardiac arrest.

SUBMITTER: Senthil K

PROVIDER: S-EPMC11325790 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model.

Senthil Kumaran K Ranganathan Abhay A Piel Sarah S Hefti Marco M MM Reeder Ron W RW Kirschen Matthew P MP Starr Jonathan J Morton Sarah S Gaudio Hunter A HA Slovis Julia C JC Herrmann Jeremy R JR Berg Robert A RA Kilbaugh Todd J TJ Morgan Ryan W RW

Resuscitation plus 20240720

<h4>Introduction</h4>Swine exhibit cerebral cortex mitochondrial dysfunction and neuropathologic injury after hypoxic cardiac arrest treated with hemodynamic-directed CPR (HD-CPR) despite normal Cerebral Performance Category scores. We analyzed the temporal evolution of plasma protein biomarkers of brain injury and inflammatory cytokines, as well as cerebral cortical mitochondrial injury and neuropathology for five days following pediatric asphyxia-associated cardiac arrest treated with HD-CPR.< ...[more]

PMID: 39149222

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Project description:ImportanceBrain injury is the leading cause of death following cardiac arrest and is associated with severe neurologic disabilities among survivors, with profound implications for patients and their families, as well as broader societal impacts. How these disabilities affect long-term survival is largely unknown.ObjectiveTo investigate whether complete neurologic recovery at hospital discharge after cardiac arrest is associated with better long-term survival compared with moderate or severe neurologic disabilities.Design, setting, and participantsThis cohort study used data from 4 mandatory national registers with structured and predefined data collection and nationwide coverage during a 10-year period in Sweden. Participants included adults who survived in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA) beyond 30 days and who underwent predefined neurologic assessment conducted by health care professionals at hospital discharge using the Cerebral Performance Category (CPC) scale between January 2010 and December 2019. Patients were divided into 3 categories: complete recovery (CPC 1), moderate disabilities (CPC 2), and severe disabilities (CPC 3-4). Statistical analyses were performed in December 2023.ExposureCPC score at hospital discharge.Main outcomes and measuresThe primary outcome was long-term survival among patients with CPC 1 compared with those with CPC 2 or CPC 3 or 4.ResultsA total of 9390 cardiac arrest survivors (median [IQR] age, 69 .0 [58.0-77.0] years; 6544 [69.7%] male) were included. The distribution of functional neurologic outcomes at discharge was 7374 patients (78.5%) with CPC 1, 1358 patients (14.5%) with CPC 2, and 658 patients (7.0%) with CPC 3 or 4. Survival proportions at 5 years were 73.8% (95% CI, 72.5%-75.0%) for patients with CPC 1, compared with 64.7% (95% CI, 62.4%-67.0%) for patients with CPC 2 and 54.2% (95% CI, 50.6%-57.8%) for patients with CPC 3 or 4. Compared with patients with CPC 1, there was significantly higher hazard of death for patients with CPC 2 (adjusted hazard ratio [aHR], 1.57 [95% CI, 1.40-1.75]) or CPC 3 or 4 (aHR, 2.46 [95% CI, 2.13-2.85]). Similar associations were seen in the OHCA and IHCA groups.Conclusions and relevanceIn this cohort study of patients with cardiac arrest who survived beyond 30 days, complete neurologic recovery, defined as CPC 1 at discharge, was associated with better long-term survival compared with neurologic disabilities at the same time point.

Project description:ObjectivesLaboratory studies suggest elevated blood pressure after resuscitation from cardiac arrest may be protective; however, clinical data are limited. We sought to test the hypothesis that elevated postresuscitation mean arterial blood pressure is associated with neurologic outcome.DesignPreplanned analysis of a prospective cohort study.SettingSix academic hospitals in the United States.PatientsAdult, nontraumatic cardiac arrest patients treated with targeted temperature management after return of spontaneous circulation.InterventionsMean arterial blood pressure was measured noninvasively after return of spontaneous circulation and every hour during the initial 6 hours after return of spontaneous circulation.Measures and main resultsWe calculated the mean arterial blood pressure and a priori dichotomized subjects into two groups: mean arterial blood pressure 70-90 and greater than 90 mm Hg. The primary outcome was good neurologic function, defined as a modified Rankin Scale less than or equal to 3. The modified Rankin Scale was prospectively determined at hospital discharge. Of the 269 patients included, 159 (59%) had a mean arterial blood pressure greater than 90 mm Hg. Good neurologic function at hospital discharge occurred in 30% of patients in the entire cohort and was significantly higher in patients with a mean arterial blood pressure greater than 90 mm Hg (42%) as compared with mean arterial blood pressure 70-90 mm Hg (15%) (absolute risk difference, 27%; 95% CI, 17-37%). In a multivariable Poisson regression model adjusting for potential confounders, mean arterial blood pressure greater than 90 mm Hg was associated with good neurologic function (adjusted relative risk, 2.46; 95% CI; 2.09-2.88). Over ascending ranges of mean arterial blood pressure, there was a dose-response increase in probability of good neurologic outcome, with mean arterial blood pressure greater than 110 mm Hg having the strongest association (adjusted relative risk, 2.97; 95% CI, 1.86-4.76).ConclusionsElevated blood pressure during the initial 6 hours after resuscitation from cardiac arrest was independently associated with good neurologic function at hospital discharge. Further investigation is warranted to determine if targeting an elevated mean arterial blood pressure would improve neurologic outcome after cardiac arrest.

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Project description:BackgroundDefinition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.MethodsSerum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent data-independent acquisition mass spectrometry analysis (DIA-MS) to find changes in serum protein concentrations associated with neurological outcome at 6-month follow-up and targeted temperature management (TTM) at 33 °C as compared to 36 °C. Neurological outcome was defined according to Cerebral Performance Category (CPC) scale as "good" (CPC 1-2, good cerebral performance or moderate disability) or "poor" (CPC 3-5, severe disability, unresponsive wakefulness syndrome, or death).ResultsOf 78 included patients [mean age 66 ± 12 years, 62 (80.0%) male], 37 (47.4%) were randomised to TTM at 36 °C. Six-month outcome was poor in 47 (60.3%) patients. The DIA-MS analysis identified and quantified 403 unique human proteins. Differential protein abundance testing comparing poor to good outcome showed 19 elevated proteins in patients with poor outcome (log2-fold change (FC) range 0.28-1.17) and 16 reduced proteins (log2(FC) between - 0.22 and - 0.68), involved in inflammatory/immune responses and apoptotic signalling pathways for poor outcome and proteolysis for good outcome. Analysis according to level of TTM showed a significant protein abundance difference for six proteins [five elevated proteins in TTM 36 °C (log2(FC) between 0.33 and 0.88), one reduced protein (log2(FC) - 0.6)] mainly involved in inflammatory/immune responses only at 48 h after cardiac arrest.ConclusionsSerum proteome profiling revealed an increase in inflammatory/immune responses and apoptosis in patients with poor outcome. In patients with good outcome, an increase in proteolysis was observed, whereas TTM-level only had a modest effect on the proteome profiles. Further validation of the differentially abundant proteins in response to neurological outcome is necessary to validate novel biomarker candidates that may predict prognosis after cardiac arrest.

Dataset Information

Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model.

Introduction

Methods

Results

Conclusions

Publications

Elevated serum neurologic biomarker profiles after cardiac arrest in a porcine model.

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