title: Investigation of muscle bioenergetics in the Marfan syndrome indicates reduced metabolic efficiency.
abstract: BACKGROUND
  The Marfan syndrome is an inherited multisystem disorder caused by mutations in fibrillin 1, with cardiovascular involvement being the most important feature of the phenoptype. Affected individuals have impaired flow-mediated dilatation (FMD) of large arteries of a similar severity to patients with chronic heart failure (CHF).
  
  
  OBJECTIVE
  Skeletal muscle bioenergetics were studied in patients with the Marfan syndrome in order to evaluate the impact of impaired flow-mediated dilatation on skeletal muscle metabolism. Skeletal muscle metabolism is abnormal in CHF and the aetiology is unclear.
  
  
  METHODS
  Thirteen patients and 12 controls were studied by phosphorus Magnetic Resonance spectroscopy of the calf muscle using an incremental exercise protocol and by Magnetic Resonance imaging.
  
  
  RESULTS
  Metabolic variables measured at rest were normal in Marfan patients. For a similar total work output measured at end of the standardized incremental exercise, the total rate of energy consumption (EC) was significantly increased in patients (21.2 +/- 2.3 mM ATP/min/W vs 13.6 +/- 1.4 mM ATP/min/W in controls). Similarly, both PCr and pH time-dependent changes were significantly different between groups. The absolute contributions of aerobic and glycolytic pathways to energy production were significantly higher in patients whereas they were similar when expressed relative to EC.
  
  
  CONCLUSIONS
  The higher EC measured in patients with Marfan syndrome was supported by both oxidative and anaerobic metabolic pathways, thereby suggesting a decrease in muscle efficiency and/or muscle mass, as previously described in other diseases affecting skeletal muscle function such as heart failure and peripheral vascular disease.
authors.affiliation: MRC Biochemical and Clinical Magnetic Resonance Unit, John Radcliffe Hospital, Oxford, United Kingdom. jenifer.crilley@cddah.nhs.uk
authors.forename: Jenifer G
authors.initials: JG
authors.lastname: Crilley
authors.forename: David
authors.initials: D
authors.lastname: Bendahan
authors.forename: Ernest A
authors.initials: EA
authors.lastname: Boehm
authors.forename: Peter
authors.initials: P
authors.lastname: Styles
authors.forename: Bheeshma
authors.initials: B
authors.lastname: Rajagopalan
authors.forename: Paul
authors.initials: P
authors.lastname: Wordsworth
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007866:Leg; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008382:Marfan Syndrome / Q000378:metabolism* / Q000503:physiopathology; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D012146:Rest
chemical_list: D010725:Phosphocreatine; D010758:Phosphorus