Towards understanding myopathy
Prolonged hospitalisation in the intensive care unit (ICU) often results in muscle wasting and weakness with some ICU patients developing critical illness myopathy (CIM). CIM is a severe complication of muscle failure which leaves patients functionally disabled long after they have been discharged from the hospital. The precise mechanisms that lead to CIM are poorly understood. However, skeletal muscle atrophy and reduced myosin heavy chain (MyHC) are consistently observed in patients with muscle failure. MyHC loss could be caused by a disturbed balance between its production and degradation through the ubiquitin-proteasome system. Based on this, scientists on the EU-funded MURF AND HYPERTROPHY project wished to investigate the turnover of MyHC in critically ill patients. They analysed skeletal muscle biopsies from ICU patients and found that even five days were sufficient to destroy myofibre ultrastructure and reduce MyHC levels. Furthermore, an increase in serum amyloid A1 was found as an early marker of CIM. These results clearly indicated that pathogenesis of muscle failure is initiated very early during critical illness and leads to an overall increase of inflammation. Taken together, the work by the MURF AND HYPERTROPHY study provided solid evidence on the mechanism and kinetics of muscle atrophy following ICU admission. Further investigation is required to evaluate the clinical outcome of certain therapeutic interventions to CIM progression.
Keywords
Critical illness myopathy, muscle atrophy, myosin heavy chain, ubiquitin-proteasome system, biopsies, serum amyloid A1
