Abstract 15237: Inhibition of the Kynurenine Pathway Improves Neurological Recovery in a Rat Model of Cardiac Arrest

Introduction: Kynurenine pathway (KP), the major route of the tryptophan (TRP) catabolism, is involved in the pathogenesis of numerous cerebral disorders. We have previously demonstrated that KP is activated following cardiac arrest (CA) and correlates with neurological injury both in animals and humans. We thus hypothesized that inhibition of the enzyme initiating the TRP catabolism into kynurenine (KYN), i.e. indoleamine-2,3-dioxygenase (IDO), could prevent KP activation and improve neurological recovery. Methods: Twenty-two rats received oral administration of 1-Methyl-Tryptophan (1-MT, 800mg/Kg of racemate) (n=10) or corresponding vehicle (n=12), 24h and 2h before CA. Ventricular fibrillation was induced and untreated for 8 min. CPR was then performed for additional 8 min prior to defibrillation. Blood samples were obtained for assay of plasma levels of: 1-MT, TRP, KYN, high-sensitive cardiac troponin T (hs-cTnT), and neuron specific enolase (NSE). Rats were observed up to 96h for assessment of neurol...