• Resuscitation · Nov 2013

    Early kynurenine pathway activation following cardiac arrest in rats, pigs, and humans.

    • Giuseppe Ristagno, Michael Fries, Laura Brunelli, Francesca Fumagalli, Renzo Bagnati, Ilaria Russo, Lidia Staszewsky, Serge Masson, Giovanni Li Volti, Agata Zappalà, Matthias Derwall, Anne Brücken, Roberta Pastorelli, and Roberto Latini.
    • Department of Cardiovascular Research, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy. Electronic address: gristag@gmail.com.
    • Resuscitation. 2013 Nov 1; 84 (11): 1604-10.

    Aim Of The StudyKynurenine 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.MethodsPlasma 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.ResultsKP 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.ConclusionIn 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.Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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