5 hours, four times per day) for 9 �� 1 days(7 to 11 days). The cross-sectional area (CSA) of the tibialis anterior (TA) muscleand electrophysiological properties of the muscle and peripheral motor nerves selleck chem Paclitaxel weremonitored during the observation period. At the end of the observation period,percutaneous muscle biopsies were taken from both the loaded and unloaded TA muscleand were analyzed for gene/protein expression, post-translational modifications(PTMs) and regulation of muscle contraction at the single muscle cell level.The purpose of this study was to better understand the mechanisms underlying CIM, andto evaluate the effects of passive mechanical loading on muscle structure andfunction in sedated and mechanically ventilated ICU patients.

We hypothesized thatmechanical silencing is a dominant factor triggering the muscle wasting and weaknessassociated with CIM in ICU patients, and that the passive mechanical loadingalleviates the muscle wasting, the preferential myosin loss and the loss in specificforce (maximum force normalized to muscle fiber CSA). The results from this studyconfirm that the ICU intervention per se (immobilization, sedation andmechanical ventilation) plays a critical role in the preferential myosin loss, amajor diagnostic feature of CIMMaterials and methodsPatients and control subjectsA total of seven mechanically ventilated ICU patients (four females and threemales, aged 56 to 67 years) numbered M1 to M7 were included in this study. Theclinical history and medications used by each patient are summarized in TableTable1.1.

Patients anticipated to require mechanicalventilation for 10 consecutive days or longer were recruited. Patients hadtypically been exposed to mechanical ventilation and immobilization for 0 to 3days (1.7 �� 0.9 days) prior to initiating the intervention and monitoringdue to delays related to obtaining signed informed consents. Patients with aprevious history of neuromuscular disease were not included in the study. Therewas no evidence of severe sepsis (sepsis with organ dysfunction) in any of thepatients according to the 2001 SCCM/ESIMC/ACCP/ATS/SIS International SepsisDefinitions Conference. None of the patients received systemic administration ofneuromuscular blocking agents, and only one patient (M1) received administrationof inhaled corticosteroids (daily dose: 1 mg) due to asthma.

Propofol wasintravenously administered in all patients.Table 1Clinical history and medications used by each ICU patientWritten informed consent was obtained from patients’ close relatives prior tobeginning the study. This study was approved by the local Ethical Committee onHuman Brefeldin_A Research at Uppsala University Hospital, Uppsala, Sweden.Muscle biopsies were obtained from the TA muscle on both the unloaded and loadedsides using the percutaneous conchotome method on the final day of theobservation period.