title: Sustained elevation of circulating growth and differentiation factor-15 and a dynamic imbalance in mediators of muscle homeostasis are associated with the development of acute muscle wasting following cardiac surgery.
abstract: OBJECTIVE
  Acute muscle wasting in the critically ill is common and causes significant morbidity. In a novel human model of acute muscle wasting following cardiac surgery, known or potential circulating modulators of muscle mass--insulin-like growth factor-1, myostatin, and growth and differentiation factor-15--were measured over a week. It was hypothesized that patients who developed acute muscle wasting would show distinct patterns of change in these mediators.
  
  
  METHODS
  A prospective longitudinal observational study of high-risk elective cardiac surgical patients identifying, by ultrasound, those developing muscle wasting.
  
  
  METHODS
  Tertiary cardiothoracic referral center: Royal Brompton Hospital, London, UK.
  
  
  METHODS
  Forty-two patients undergoing elective high-risk cardiothoracic surgery.
  
  
  METHODS
  Circulating insulin-like growth factor-1, myostatin, and growth and differentiation factor-15 were assayed preoperatively and over the first week postoperatively. The ability of growth and differentiation factor-15 to cause muscle wasting in vitro was determined in C2C12 myotubes.
  
  
  RESULTS
  Of the 42 patients, 23 (55%) developed quadriceps atrophy. There was an acute decrease in insulin-like growth factor-1 and unexpectedly myostatin, known mediators of muscle hypertrophy and atrophy, respectively. By contrast, plasma growth and differentiation factor-15 concentrations increased in all patients. This increase in growth and differentiation factor-15 was sustained at day 7 in those who developed muscle wasting (day 7 compared with baseline, p<0.01), but recovered in the nonwasting group (p>0.05). Insulin-like growth factor-1 did not recover in those who developed muscle wasting (day 7 compared with baseline, p<0.01) but did in the nonwasting group (p>0.05). Finally, we demonstrated that growth and differentiation factor-15 caused atrophy of myotubes in vitro.
  
  
  CONCLUSIONS
  These data support the hypothesis that acute muscle loss occurs as a result of an imbalance between drivers of muscle atrophy and hypertrophy. Growth and differentiation factor-15 is a potential novel factor associated with muscle atrophy, which may become a therapeutic target in patients with ICU acquired paresis and other forms of acute muscle wasting.
authors: Molecular Medicine, National Heart and Lung Institute, Imperial College, London, UK. susannah.bloch@doctors.org.uk
authors: Susannah A A
authors: SA
authors: Bloch
authors: Jen Y
authors: JY
authors: Lee
authors: S John
authors: SJ
authors: Wort
authors: Michael I
authors: MI
authors: Polkey
authors: Paul R
authors: PR
authors: Kemp
authors: Mark J D
authors: MJ
authors: Griffiths
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D005260:Female; D006706:Homeostasis; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D051741:Kruppel-Like Transcription Factors / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D018908:Muscle Weakness / Q000097:blood / Q000209:etiology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D055435:Myostatin / Q000097:blood; D009687:Nuclear Proteins / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D006113:United Kingdom
chemical_list: D015415:Biomarkers; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; C414172:KLF15 protein, human; D051741:Kruppel-Like Transcription Factors; D055435:Myostatin; D009687:Nuclear Proteins