Early kynurenine pathway activation following cardiac arrest in rats, pigs, and humans.
AIM OF THE STUDY
Kynurenine pathway (KP) is a major route of the tryptophan (TRP) catabolism. In the present study, TRP and KP metabolites concentrations were measured in plasma from rats, pigs and humans after cardiac arrest (CA) in order to assess KP activation and its potential role in post-resuscitation outcome.


METHODS
Plasma was obtained from: (A) 24 rats, subjected to 6 min CA and 6 min of cardiopulmonary resuscitation (CPR); (B) 10 pigs, subjected to 10 min CA and 5 min CPR; and (C) 3 healthy human volunteers and 5 patients resuscitated from CA. KP metabolites were quantified by liquid chromatography multiple reaction monitoring mass spectrometry. Assessments were available at baseline, and 1-4h, and 3-5 days post-CA.


RESULTS
KP was activated after CA in rats, pigs, and humans. Decreases in TRP occurred during the post-resuscitation period and were accompanied by significant increases in its major metabolites, 3-hydroxyanthranilic acid (3-HAA) and kynurenic acid in each species, that persisted up to 3-5 days post-CA (p<0.01). In rats, changes in KP metabolites reflected changes in post-resuscitation myocardial function. In pigs, changes in TRP and increases in 3-HAA were significanlty related to the severity of cerebral histopathogical injuries. In humans, KP activation was observed, together with systemic inflammation. Post-CA increases in 3-HAA were greater in patients that did not survive.


CONCLUSION
In this fully translational investigation, the KP was activated early following resuscitation from CA in rats, pigs, and humans, and might have contributed to post-resuscitation outcome.
['Ristagno|Giuseppe|G|', 'Fries|Michael|M|', 'Brunelli|Laura|L|', 'Fumagalli|Francesca|F|', 'Bagnati|Renzo|R|', 'Russo|Ilaria|I|', 'Staszewsky|Lidia|L|', 'Masson|Serge|S|', 'Li Volti|Giovanni|G|', 'Zappalà|Agata|A|', 'Derwall|Matthias|M|', 'Brücken|Anne|A|', 'Pastorelli|Roberta|R|', 'Latini|Roberto|R|']
D000818:Animals D016887:Cardiopulmonary Resuscitation D002853:Chromatography, Liquid D006323:Heart Arrest D006439:Hemodynamics D006801:Humans D007737:Kynurenine D008297:Male D013058:Mass Spectrometry D017207:Rats, Sprague-Dawley D015996:Survival Rate D013552:Swine
Kynurenine pathway Cardiac arrest Tryptophan Outcome Brain injury Post cardiac arrest syndrome