Early administration of cisatracurium attenuates sepsis-induced diaphragm dysfunction in rats

Sepsis can often induce diaphragm dysfunction, which is associated with localized elaboration of cytokines within the diaphragm. The administration of cisatracurium has been shown to decrease the inflammatory response and to facilitate mechanical ventilation. In this study, we explored whether cisatracurium could attenuate sepsis-induced diaphragm dysfunction in rats. Animals were divided into three groups: (1) the control group: rats underwent a sham surgical procedure with cecal exposure, but the cecum was neither ligated nor punctured; (2) the CLP group: rats underwent cecal ligation and puncture (CLP) and received a continuous infusion of NaCl 0.9 %; and (3) the Cis + CLP group: rats underwent CLP and received a continuous infusion of cisatracurium. After the surgical procedure, all animals underwent controlled mechanical ventilation for 18 h. Plasma concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-mobility group box 1 (HMGB1) were measured using an enzyme-linked immunosorbent assay. Upon completion of the experimental protocol, diaphragm contractility and HMGB1 protein expression were analyzed. Impaired diaphragm contractile function, including both force-related properties and force-frequency responses, was pronounced after CLP in comparison with that observed in the control rats. Furthermore, CLP elevated serum levels of IL-6, TNF-α, and HMGB1, and induced HMGB1 protein expression in the diaphragm. In contrast, cisatracurium counteracted the sepsis-induced inflammation reaction in the diaphragm and serum and maintained diaphragm function. These data suggest that early infusion of cisatracurium attenuates sepsis-induced diaphragm dysfunction; this may be attributable to its anti-inflammatory action.