Abstract 10881: Metabolomics of Cardiac Arrest in Ex-Vivo Canine Model of Long-Duration Ventricular Fibrillation (VF)
Long duration VF (LDVF) deteriorating into asystole is a typical and arguably one of the most adverse scenarios of cardiac arrest. Yet, metabolic determinants of asystole in the context of LDVF are largely unknown. We sought to determine key metabolic alterations associated with the incidence of asystole during 20-min of global ischemia and VF in blood-perfused dog hearts (n=9). Tissue samples were obtained from anterior left ventricular epicardium at 20 seconds and 2, 5, 10, and 20 min of ischemia. We used gas chromatography mass-spectrometry, high performance liquid chromatography, and biochemical assays to analyze 42 metabolites (high energy phosphates, adenine nucleotides, the substrates and intermediates of glycolysis and Krebs cycle, amino acids, and fatty acids). Mid-myocardial VF activation rate (VFR) was determined using plunge needle electrodes. Asystole was defined as spontaneous LDVF termination followed by complete electrical standstill or sporadic rhythm < 20 beats/min (Fig. A). Cluster analysis revealed dichotomy in the timing of asystole. Four out of 9 hearts experienced asystole at 8.8 ± 0.7 min of ischemia (EARLY ASYS), while the remaining 5 hearts maintained VF over 19.6 min of ischemia (LATE ASYS). Among all tested metabolites, only ADP, phosphocreatine (PCr), glucose, lactate and citrate were significantly different between EARLY ASYS and LATE ASYS (Figs. B-F). Specifically, EARLY ASYS hearts had lower PCr, higher ADP and higher tissue glucose at 20 sec of ischemia; higher glucose consumption (Δglucose) from 20 s to 2 min of ischemia; higher lactate at 2, 5 and 20 min of ischemia; and higher citrate at 2 and 10 min of ischemia. In all hearts VFR was inversely correlated with lactate level (R=0.86). We conclude that lactate accumulation due to enhanced glycolysis is the key metabolic determinant of electrical depression and asystole during LDVF. In turn, the rate of glycolysis may depend on the degree of energy imbalance occurring soon after LDVF onset.
- © 2011 by American Heart Association, Inc.