12,13-diHOME Is Increased During Targeted Temperature Management And Correlates With Survival After Cardiac Arrest Resuscitation

CONTEXT: Trials of targeted temperature management (TTM) after cardiac arrest (CA) have had conflicting results. Brown adipose tissue (BAT) is a thermogenic organ activated by cold temperature to regulate body temperature, systemic metabolism and the immune system. Approximately 10-30% of adult patients have BAT and this heterogeneity may explain variable treatment to TTM. OBJECTIVE: This study sought to measure differences in outcome, metabolic and immune activation between patients treated with TTM following CA with varying BAT activity, measured through BAT-associated lipid 12,13-diHOME concentrations in circulation. DESIGN: BAT biomarker 12,13-diHOME was quantified using liquid chromatography-mass spectrometry (LC-MS) on plasma from 74 patients at various time points starting at 6 hours and up until 7 days after return of spontaneous circulation (ROSC). Additionally, circulating glucose, C-peptide and fatty acids were measured by glucometer, ELISA and LC-MS, respectively. Peripheral blood mononuclear cells were analyzed by flow cytometry. RESULTS: 12,13-diHOME was increased in patients treated with TTM at 33°C and positively correlated with favorable outcomes. 12,13-diHOME levels peaked in the first 12 to 48 hours and decreased below the first post-ROSC level by 7 days. Glucose homeostasis was not associated with 12,13-diHOME levels. In a subset of patients, we could detect a specific phospholipid signature in patients with higher 12,13-diHOME. Patients with higher 12,13-diHOME also had increased mature neutrophils and lower immature neutrophils. CONCLUSIONS: Circulating 12,13-diHOME levels are increased in some patients undergoing targeted temperature management after cardiac arrest, which may be indicative of increased BAT activity. 12,13-diHOME is associated with survival, alterations of phospholipid metabolism, and a profile of less activated immune system. BAT may mediate the effects of temperature management on outcome after cardiac arrest.