Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients
(2022) In Resuscitation 179. p.163-171- Abstract
Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death. Even if successfully resuscitated, mortality remains high due to ischemic and reperfusion injury (I/R). The oxygen deprivation leads to a metabolic derangement amplified upon reperfusion resulting in an uncontrolled generation of reactive oxygen species in the mitochondria triggering cell death mechanisms. The understanding of I/R injury in humans following OHCA remains sparse, with no existing treatment to attenuate the reperfusion injury. Aim: To describe metabolic derangement in patients following resuscitated OHCA. Methods: Plasma from consecutive resuscitated unconscious OHCA patients drawn at hospital admission were analyzed using... (More)
Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death. Even if successfully resuscitated, mortality remains high due to ischemic and reperfusion injury (I/R). The oxygen deprivation leads to a metabolic derangement amplified upon reperfusion resulting in an uncontrolled generation of reactive oxygen species in the mitochondria triggering cell death mechanisms. The understanding of I/R injury in humans following OHCA remains sparse, with no existing treatment to attenuate the reperfusion injury. Aim: To describe metabolic derangement in patients following resuscitated OHCA. Methods: Plasma from consecutive resuscitated unconscious OHCA patients drawn at hospital admission were analyzed using ultra-performance-liquid-mass-spectrometry. Sixty-one metabolites were prespecified for quantification and studied. Results: In total, 163 patients were included, of which 143 (88%) were men, and the median age was 62 years (53–68). All measured metabolites from the tricarboxylic acid (TCA) cycle were significantly higher in non-survivors vs. survivors (180-days survival). Hierarchical clustering identified four clusters (A-D) of patients with distinct metabolic profiles. Cluster A and B had higher levels of TCA metabolites, amino acids and acylcarnitine species compared to C and D. The mortality was significantly higher in cluster A and B (A:62% and B:59% vs. C:21 % and D:24%, p < 0.001). Cluster A and B had longer time to return of spontaneous circulation (A:33 min (21–43), B:27 min (24–35), C:18 min (13–28), and D:18 min (12–25), p < 0.001). Conclusion: Circulating levels of metabolites from the TCA cycle best described the variance between survivors and non-survivors. Four different metabolic phenotypes with significantly different mortality were identified.
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- author
- Paulin Beske, Rasmus ; Henriksen, Hanne H. ; Obling, Laust ; Kjærgaard, Jesper ; Bro-Jeppesen, John ; Nielsen, Niklas LU ; Johanson, Pär I. and Hassager, Christian
- organization
- publishing date
- 2022-10-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Lipid metabolites, Metabolomics, Out-of-hospital cardiac arrest, Tricarboxylic acid
- in
- Resuscitation
- volume
- 179
- pages
- 9 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:35753507
- scopus:85133399006
- ISSN
- 0300-9572
- DOI
- 10.1016/j.resuscitation.2022.06.010
- language
- English
- LU publication?
- yes
- id
- 9d475f92-3021-4d3e-a8b1-f2cecfdb8a80
- date added to LUP
- 2022-10-04 09:25:51
- date last changed
- 2024-06-27 17:27:00
@article{9d475f92-3021-4d3e-a8b1-f2cecfdb8a80,
abstract = {{<p>Background: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death. Even if successfully resuscitated, mortality remains high due to ischemic and reperfusion injury (I/R). The oxygen deprivation leads to a metabolic derangement amplified upon reperfusion resulting in an uncontrolled generation of reactive oxygen species in the mitochondria triggering cell death mechanisms. The understanding of I/R injury in humans following OHCA remains sparse, with no existing treatment to attenuate the reperfusion injury. Aim: To describe metabolic derangement in patients following resuscitated OHCA. Methods: Plasma from consecutive resuscitated unconscious OHCA patients drawn at hospital admission were analyzed using ultra-performance-liquid-mass-spectrometry. Sixty-one metabolites were prespecified for quantification and studied. Results: In total, 163 patients were included, of which 143 (88%) were men, and the median age was 62 years (53–68). All measured metabolites from the tricarboxylic acid (TCA) cycle were significantly higher in non-survivors vs. survivors (180-days survival). Hierarchical clustering identified four clusters (A-D) of patients with distinct metabolic profiles. Cluster A and B had higher levels of TCA metabolites, amino acids and acylcarnitine species compared to C and D. The mortality was significantly higher in cluster A and B (A:62% and B:59% vs. C:21 % and D:24%, p < 0.001). Cluster A and B had longer time to return of spontaneous circulation (A:33 min (21–43), B:27 min (24–35), C:18 min (13–28), and D:18 min (12–25), p < 0.001). Conclusion: Circulating levels of metabolites from the TCA cycle best described the variance between survivors and non-survivors. Four different metabolic phenotypes with significantly different mortality were identified.</p>}},
author = {{Paulin Beske, Rasmus and Henriksen, Hanne H. and Obling, Laust and Kjærgaard, Jesper and Bro-Jeppesen, John and Nielsen, Niklas and Johanson, Pär I. and Hassager, Christian}},
issn = {{0300-9572}},
keywords = {{Lipid metabolites; Metabolomics; Out-of-hospital cardiac arrest; Tricarboxylic acid}},
language = {{eng}},
month = {{10}},
pages = {{163--171}},
publisher = {{Elsevier}},
series = {{Resuscitation}},
title = {{Targeted plasma metabolomics in resuscitated comatose out-of-hospital cardiac arrest patients}},
url = {{http://dx.doi.org/10.1016/j.resuscitation.2022.06.010}},
doi = {{10.1016/j.resuscitation.2022.06.010}},
volume = {{179}},
year = {{2022}},
}