Observational studyJournal of the American Heart Association2014
Early activation of the kynurenine pathway predicts early death and long-term outcome in patients resuscitated from out-of-hospital cardiac arrest.
Observational study in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Effects of tryptophan, serotonin, and kynurenine on ischemic heart diseases and its risk factors: a Mendelian Randomization study.European journal of clinical nutrition · 2020Pooled it
- Metabolomic signatures prior to in-hospital cardiac arrest: insights into potential therapeutic targets.Scientific reports · 2026Article
- Impact of heart failure on skeletal muscle: an overview.Journal of geriatric cardiology : JGC · 2026Article
- An untargeted metabolomics analysis suggests pathophysiological changes for post cardiac arrest syndrome.Resuscitation plus · 2025Article
- Metabolic effects of high-dose glucocorticoid following out-of-hospital cardiac arrest.Intensive care medicine experimental · 2025Article
- Multi-omics Study of Hypoxic-Ischemic Brain Injury After Cardiopulmonary Resuscitation in Swine.Neurocritical care · 2025Article
- Kynurenic Acid/AhR Signaling at the Junction of Inflammation and Cardiovascular Diseases.International journal of molecular sciences · 2024Review
- Wolf Creek XVII Part 8: Neuroprotection.Resuscitation plus · 2024Review
- Indoleamine 2,3-Dioxygenase Deletion to Modulate Kynurenine Pathway and to Prevent Brain Injury after Cardiac Arrest in Mice.Anesthesiology · 2023Article
- Life-Threatening Cardiogenic Shock Related to Venlafaxine Poisoning-A Case Report with Metabolomic Approach.Metabolites · 2023Article
- Brain Kynurenine Pathway and Functional Outcome of Rats Resuscitated From Cardiac Arrest.Journal of the American Heart Association · 2021Article
- Crosstalk between Tryptophan Metabolism via Kynurenine Pathway and Carbohydrate Metabolism in the Context of Cardio-Metabolic Risk-Review.Journal of clinical medicine · 2021Review
- Pharmacological Approach for Neuroprotection After Cardiac Arrest-A Narrative Review of Current Therapies and Future Neuroprotective Cocktail.Frontiers in medicine · 2021Review
- Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease.Frontiers in immunology · 2021Review
- Ventilation With Argon Improves Survival With Good Neurological Recovery After Prolonged Untreated Cardiac Arrest in Pigs.Journal of the American Heart Association · 2020Article
- Plasma metabolomics supports the use of long-duration cardiac arrest rodent model to study human disease by demonstrating similar metabolic alterations.Scientific reports · 2020Article
- Activation of kynurenine pathway of tryptophan metabolism after infant cardiac surgery with cardiopulmonary bypass: a prospective cohort study.Metabolomics : Official journal of the Metabolomic Society · 2020Article
- Hepatic steatosis induced in C57BL/6 mice by a non-ß oxidizable fatty acid analogue is associated with reduced plasma kynurenine metabolites and a modified hepatic NADLipids in health and disease · 2020Article
- Trisomy 21 activates the kynurenine pathway via increased dosage of interferon receptors.Nature communications · 2019Article
- Metabolomic Fingerprinting of Infants Undergoing Cardiopulmonary Bypass: Changes in Metabolic Pathways and Association With Mortality and Cardiac Intensive Care Unit Length of Stay.Journal of the American Heart Association · 2018Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post-cardiac arrest shock, early death, and long-term outcome. METHODS AND
resultsPlasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12-month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3-hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3-hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3-hydroxyanthranilic acid had lower 24-hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3-hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12-month poor outcome and significantly improved risk reclassification.
conclusionsKP is activated early after cardiac arrest and is associated with severity of post-cardiac arrest shock, early death, and poor long-term outcome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.