RT Journal Article
SR Electronic
T1 High dose methylprednisolone counteracts the negative effect of rocuronium on diaphragm function in a rat model of mechanical ventilation
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p5002
VO 38
IS Suppl 55
A1 Karen Maes
A1 Dries Testelmans
A1 Debby Thomas
A1 Marc Decramer
A1 Ghislaine Gayan-Ramirez
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p5002.abstract
AB Rationale: We previously showed that rocuronium (ROC) combined with 24h of controlled mechanical ventilation leads to an additional negative effect on diaphragm function in rats. Based on clinical observations we hypothesized that the combination of rocuronium with corticosteroids in our animal model of CMV would result into a further deterioration of diaphragm function.Methods: Mechanically ventilated (24h) rats received intravenously either a continuous infusion of saline (CMV) or ROC or ROC combined with an intramuscular injection of 80 mg/kg of methylprednisolone (ROC-MP).Results: ROC treatment resulted in a significant reduction of diaphragm force compared with CMV. Treatment with MP attenuated the ROC-induced contractile dysfunction of the diaphragm. Cross-sectional area of the diaphragm type IIx/b fibres tended to decrease with 13% after ROC compared with the other groups. Diaphragm MURF-1 mRNA expression was significantly increased with 30% after ROC and ROC-MP compared to CMV while MAFbx was similar in all groups. Diaphragm caspase-3 activity (+ 39%) and calpain activity (+99%) were increased after ROC compared to CMV. Treatment with MP abolished the increase in caspase-3 and calpain activity. Proteolytic activity in the gastrocnemius was similar in all groups. The ratio of MyHC to actin was similar in the diaphragm and the gastrocnemius in all groups.Conclusions: The additional negative effect of ROC on the diaphragm during CMV is abolished with administration of a high dose of MP. This effect is most likely due to an inhibition of the calpain and caspase-3 system.Funded by: FWO-Vlaanderen G.0197.07 and AstraPharmaceuticals