Abstract 201: Specific Metabolic Pathways Involved in Outcome of Cardiopulmonary Resuscitation: A Pilot Plasma Metabolomic Study in a Rat Model of Cardiac Arrest and CPR

Abstract

Introduction. The mechanisms responsible for postresuscitation myocardial and cerebral dysfunction are not well understood. We hypothesized that untargeted plasma metabolomic analyses would be a feasible approach to identify perturbations in circulating metabolites and thus potential mechanisms accounting for outcome of cardiac arrest (CA). Methods. Six male rats, 440 ± 50 g, were used. Ventricular fibrillation was induced in 3 rats and was untreated for 6 mins. CPR, including mechanical chest compressions, ventilations and epinephrine, was then initiated and continued for additional 6 mins prior to defibrillation. Two hrs following resuscitation, animals were sacrificed and plasma collected. The other 3 rats were not subjected to cardiac arrest and served as controls. Plasma metabolome was examined by liquid chromatography-tandem mass spectrometry. Differences in chromatogram profiles were then analyzed using SIEVE v1.3 analysis software. Chromatographic peaks, with accurate masses, retention time and tandem mass fragmentation patterns were then identified using mass-spectral libraries of metabolites. Results. A total of 523 chromatographic peaks showed significant differences after CA. Changes in metabolites participating in purine/pyrimidine metabolism, glycolisis, TCA cycle, pentose phosphate pathways, cholesterols and derivatives, lipids, and fatty acid oxidation, were observed. Changes in long-chain acylcarnitine and corticosterone/cortisol levels were also found, suggesting oxidative damages and deregulation of hypothalamic-pituitary-adrenal axis, respectively. More importantly, numerous metabolites along the kynurenine pathway from tryptophan oxidation, typically related to neurological degeneration, were identified (Figure). Conclusions. In this pilot study, plasma metabolomics allowed for identification of specific metabolic pathways, i.e. tryptophan pathway, that ultimately may contribute to CA outcome.