title: Loss of capacity to recover from acidosis in repeat exercise is strongly associated with fatigue in primary biliary cirrhosis.
abstract: OBJECTIVE
  Upon exercise, primary biliary cirrhosis (PBC) is associated with significant acidosis in peripheral muscle with recovery rate from acidosis strongly associating with fatigue. PBC patients describe particular problems with repeat exercise describing subsequent exercise episodes being limited by perceived effects of the first. We modelled this effect by exploring kinetics of pH recovery during 3 linked exercise episodes using magnetic resonance spectroscopy (MRS).
  
  
  METHODS
  Muscle acid handling capacity was studied following 3 x 3 min exercise periods at 35% maximum voluntary capacity in matched fatigued PBC, non-fatigued PBC and healthy controls (n=8 per group).
  
  
  RESULTS
  Time to pH recovery following initial exercise was prolonged in PBC compared to controls (160 s [60-390] vs. 25 [0-180], p=0.005) with the longest recovery time seen in fatigued patients (median 210 s). All subjects shortened recovery time between exercise periods 1-2 (controls: mean -28%, non-fatigued PBC patients: -29% and fatigued PBC patients: -30%. Normals showed further recovery shortening between exercise periods 2-3 (-18%, p=ns vs. period 1-2 recovery) however this adaptive response was lost in non-fatigued PBC patients (+3%) and reversed in fatigued patients (+19%, p=0.01 vs. period 1-2).
  
  
  CONCLUSIONS
  PBC patients retain the physiological capacity to shorten pH recovery time following repeat exercise. Capacity to shorten recovery time after a 2nd exercise period is lost in low-fatigue PBC patients and replaced by recovery prolongation in fatigued patients. Improvement in post-exercise acid recovery through exercise therapy should be possible in PBC patients and could be a novel approach to peripheral fatigue treatment.
authors.affiliation: Newcastle Magnetic Resonance Centre, Newcastle University, UK.
authors.forename: Kieren G
authors.initials: KG
authors.lastname: Hollingsworth
authors.forename: Julia L
authors.initials: JL
authors.lastname: Newton
authors.forename: Lisa
authors.initials: L
authors.lastname: Robinson
authors.forename: Roy
authors.initials: R
authors.lastname: Taylor
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.forename: David E J
authors.initials: DE
authors.lastname: Jones
mesh_terms: D000138:Acidosis / Q000209:etiology* / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004734:Energy Metabolism; D015444:Exercise / Q000502:physiology*; D005081:Exercise Therapy; D005221:Fatigue / Q000209:etiology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008105:Liver Cirrhosis, Biliary / Q000150:complications* / Q000503:physiopathology* / Q000628:therapy; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D018763:Muscle Fatigue / Q000502:physiology; D018482:Muscle, Skeletal / Q000503:physiopathology