High dose methylprednisolone counteracts the negative effects of rocuronium on diaphragm function

Abstract

We previously showed that rocuronium combined with 24 h of controlled mechanical ventilation (CMV) leads to an additional negative effect on diaphragm function in rats. Based on clinical observations we examined whether the combination of rocuronium with corticosteroids during CMV would result into a further deterioration of diaphragm function. Mechanically ventilated rats received intravenously a continuous infusion of saline (CMV) or rocuronium (ROC) or rocuronium combined with an intramuscular injection of 80 mg/kg of methylprednisolone (ROC-MP). After 24 h we determined diaphragm in vitro contractile properties, cross-sectional area (CSA) of the different fiber types, the MyHC/actin ratio, and proteolytic activity in diaphragm and gastrocnemius. ROC treatment resulted in a significant reduction of diaphragm force compared with CMV. Treatment with MP attenuated the ROC-induced diaphragmatic contractile dysfunction. CSA of the diaphragm type IIx/b fibers tended to decrease by 13% after ROC but not after MP. Diaphragm MuRF-1 mRNA expression increased significantly with 30% after ROC and ROC-MP compared to CMV, while MAFbx was similar in all groups. Diaphragm caspase-3 (+39%) and calpain activity (+99%) were increased after ROC compared to CMV. Treatment with MP abolished the increase in both activities. Proteolytic activity in the gastrocnemius was similar in all groups. The MyHC/actin ratio was similar in the diaphragm and the gastrocnemius in all groups. The combination of ROC with a high dose of MP attenuated diaphragm dysfunction caused by ROC probably through inhibition of the calpain and caspase-3 system. None of these treatments affected the gastrocnemius.