Abstract 72: Muscle Metabolomic Changes in a Porcine Model of Hemorrhagic Shock and Resuscitation

Abstract

Introduction: Treatment of hemorrhage shock remains a clinical challenge despite decades of study. Investigation of metabolism during hemorrhagic shock and resuscitation may yield novel approaches for intervention strategies. Methods: Pigs underwent a standardized hemorrhagic shock protocol after general anesthesia and instrumentation. Animals were hemorrhaged via IVC cannula, then resuscitated to a goal of 80 mm Hg systolic blood pressure after 45 minutes. Animals were fully resuscitated after 8 hours and weaned and extubated at 24 hours after beginning experiment. Survivors were sacrificed at 48 hours post-hemorrhage. Muscle samples were obtained at baseline (prior to hemorrhage), shock45 (after 45 min of shock), and 8, 23, and 48 h post resuscitation (PR). Muscle samples were processed using a dual-phase extraction process and the water-soluble metabolites examined by 1H and 31P NMR. Results: The phosphocreatine:inorganic phosphate ratio decreases with shock and remains below baseline values at 48 h PR (A). Phosphoesters (glycolytic intermediates) increase during shock and return to levels below baseline at 48PR in successfully resuscitated pigs (B). Non-survivors exhibited higher levels of 1H NMR-visible lipids and of 31P NMR-visible ADP at baseline when compared to survivors (C). Conclusions: Hemorrhage shock induces metabolic changes observable with NMR spectroscopy. Survivors exhibited persistent metabolic changes not resolved at 48 hours. Response to hemorrhage and risk of mortality may be dependent on initial metabolic state.