Cerebral net uptake of lactate contributes to neurological injury after experimental cardiac arrest in rabbits.
Astrocytes
Cardiac arrest
Fluorocitrate
Lactate
Neuroprotection
Oxamate
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 Oct 2024
19 Oct 2024
Historique:
received:
04
06
2024
accepted:
27
09
2024
medline:
20
10
2024
pubmed:
20
10
2024
entrez:
19
10
2024
Statut:
epublish
Résumé
During focal ischemia, neurons can use lactate as an alternative source of energy through its oxidation into pyruvate by the lactate dehydrogenase (LDH). After cardiac arrest, the neurological consequences of this phenomenon are unknown. Experimental study. Experimental laboratory. Male New-Zealand rabbits. Animals were surgically instrumented and randomly divided into five groups receiving short infusion duration of either lactate or pyruvate or a pre-cardiac arrest infusion of oxamate (an inhibitor of the lactate dehydrogenase) or injection of fluorocitrate (an inhibitor of astrocytic tricarboxylic acid), or Saline (lactate, pyruvate, Oxa, FC and Control groups, respectively). After randomization, animals were submitted to 10 min of ventricular fibrillation and subsequent resuscitation. All animals were then either followed during 4 h, for the evaluation of the cerebral net uptake and concentrations of metabolites by microdialysis (n = 6 in each experimental group, n = 12 in control group), or during 48 h for the evaluation of their neurological outcome (n = 7 in each groups and n = 14 in control group). Cardiac arrest was associated with a dramatic increase in cerebral net uptake of lactate during 120 min after resuscitation, which was increased by lactate or pyruvate administration. This was associated with an increase in the mean neurological dysfunction score (66.7 ± 4.7, 79.0 ± 4.5 vs 57.7 ± 1.5 in Lactate, Pyruvate and Control group respectively) at 48 h after cardiac arrest. Oxamate and FC administration were associated with a lower lactate cerebral uptake after cardiac arrest and with an improvement of the neurological recovery (28.85 ± 9.4, 23.86 ± 6.2 vs 57.7 ± 1.5 in Oxa, FC and Control group respectively). After cardiac arrest, immediate isotonic lactate or pyruvate administration is deleterious. Pre-cardiac arrest LDH inhibition was potently neuroprotective in this setting.
Identifiants
pubmed: 39426990
doi: 10.1038/s41598-024-74660-6
pii: 10.1038/s41598-024-74660-6
doi:
Substances chimiques
Lactic Acid
33X04XA5AT
Pyruvic Acid
8558G7RUTR
Oxamic Acid
QU60N5OPLG
fluorocitrate
357-89-1
L-Lactate Dehydrogenase
EC 1.1.1.27
Citrates
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
24600Informations de copyright
© 2024. The Author(s).
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