Dexmedetomidine post-treatment exacerbates metabolic disturbances in septic cardiomyopathy via α2A-adrenoceptor.

Cardiomyopathy is a common complication and significantly increases the risk of death in septic patients. Our previous study demonstrated that post-treatment with dexmedetomidine (DEX) aggravates septic cardiomyopathy. However, the mechanisms for the side effect of DEX post-treatment on septic cardiomyopathy are not well-defined. Here we employed a cecal ligation and puncture (CLP) model and α 2A -adrenoceptor deficient (Adra2a -/- ) mice to observe the effects of DEX post-treatment on myocardial metabolic disturbances in sepsis. CLP mice displayed significant cardiac dysfunction, altered mitochondrial dynamics, reduced cardiac lipid and glucose uptake, impaired fatty acid and glucose oxidation, enhanced glycolysis and decreased ATP production in the myocardium, almost all of which were dramatically enhanced by DEX post-treatment in septic mice. In Adra2a -/- mice, DEX post-treatment did not affect cardiac dysfunction and metabolic disruptions in CLP-induced sepsis. Additionally, Adra2a -/- mice exhibited impaired cardiac function, damaged myocardial mitochondrial structures, and disturbed fatty acid metabolism and glucose oxidation. In sum, DEX post-treatment exacerbates metabolic disturbances in septic cardiomyopathy in a α 2A -adrenoceptor dependent manner. [Display omitted] • Dexmedetomidine (DEX) post-treatment deteriorates cardiac dysfunction in septic mice. • DEX post-treatment worsens myocardial mitochondrial injury induced by sepsis. • DEX exacerbates disorders of fatty acids and glucose metabolism in septic myocardium. • DEX activates α 2A -adrenoceptor to aggravate metabolic disturbances in septic heart. [ABSTRACT FROM AUTHOR]