Abstract 14: Activation of the Kynurenine Pathway in Patients Resuscitated From Ventricular Fibrillation Out-of-hospital Cardiac Arrest
The kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism, mainly activated by inflammation. We hypothesized that the KP is activated after cardiac arrest (CA) and correlates with time to return of spontaneous circulation (ROSC), severity of shock and long term outcome.
Methods: Blood samples were obtained at intensive care unit (ICU) admission from 155 out-of-hospital CA patients enrolled in a prospective multicenter observational trial including 21 ICUs in Finland (FINNRESUSCI study). Time to ROSC, lowest systolic arterial pressure (SAP) and lowest bicarbonate (BIC) levels during the first 24 hrs were recorded. Poor outcome was defined as cerebral performance category (CPC) of 3-5 at 12 months. Plasma levels of TRP and its metabolites kynurenine (KYN), kynurenic acid (KYNA) and 3-hydroxyanthranilicic acid (3-HAA) were measured by liquid chromatography and mass spectrometry. The KYN to TRP ratio was calculated. Non-parametrc tests, univariate, multivariate and linear regression analysis were used to determine associations of KP and study endpoints.
Result: The levels of KP metabolites were significantly higher in patients with CPC 3-5 compared to CPC 1-2 (KYN, p<0.001, KYNA p=0.043, KYN/TRP p<0.001, 3-HAA p=0.047, respectively). Time to ROSC correlated with KYN (p=0.005), KYNA (0.023), 3-HAA (p=0.011) and KYN/TRP (p=0.015). Patients with higher levels of KYN, KYNA, and KYN/TRP, had lower 24 hr SAP and BIC. With logistic regression, KYNA (net reclassification index, NRI 0.66,p<0.0001) and 3-HAA (NRI 0.56, p=0.0006) were independent predictors of outcome (Table).
Conclusions: The KP may be an important pathophysiological pathway activated after CA and its metabolites KYNA and 3-HAA have important prognostic implications.
- © 2013 by American Heart Association, Inc.