Studies on novel biomarkers of myocardial dysfunction caused by adrenaline through metabolomics

Epinephrine is important in resuscitation therapy and improves the return of spontaneous circulation after cardiac arrest, but its safety remains an important concern because high doses of epinephrine may worsen myocardial dysfunction, and the underlying pathophysiology remains unclear. In this study, we found that the addition of 1 mg/kg, 2 mg/kg, and 3 mg/kg exogenous adrenaline could induce myocardial dysfunction in rats, and 1 mg/kg adrenaline was the minimum and optimal dose for establishing a myocardial dysfunction model. Through a nontargeted metabolomics approach, we performed a myocardial dysfunction model under 1 mg/kg and identified several associated metabolic pathways, including pyruvate metabolism, regulation of lipolysis in adipocytes and biosynthesis of unsaturated fatty acids. The metabolites of lactate and fatty acids such as cis-9-palmitoleic acid, eicosapentaenoic acid and 2-methyl-3-hydroxybutyric acid were significantly enriched in the epinephrine-treated group compared to the control group ( P  < 0.05), while carnitines, including L-palmitoylcarnitine, acetylcarnitine and stearoylcarnitine, were significantly depleted in the serum of the epinephrine-treated rats ( P  < 0.05). A dose-dependent effect of adrenaline on myocardial dysfunction was observed, and further analysis of these metabolites may indicate their suitability as novel diagnostic biomarkers for myocardial dysfunction caused by adrenaline.