title: A potential role for free radical-mediated skeletal muscle soreness in the pathophysiology of acute mountain sickness.
abstract: BACKGROUND
  It has been suggested that free radicals may be implicated in the pathophysiology of acute mountain sickness (AMS) due to their ability to initiate and propagate cell membrane damage (3). Therefore, the present study was designed to: a) investigate the effects of an expedition to high altitude on metabolic indices of free radical-mediated oxidative stress and assess subsequent implications for skeletal/cardiac muscle damage; and b) determine whether these parameters were different in subjects who developed AMS after gradual ascent to 5100 m (base camp, BC) compared with those who remained healthy.
  
  
  METHODS
  There were 19 male volunteers who were examined at rest and after a standardized maximal exercise test at sea level before and after an expedition (SL1/SL2) and during the first morning of arrival at BC. The trek to BC lasted 20+/-5 d.
  
  
  RESULTS
  A mild increase in the Lake Louise AMS score was observed by the end of day 1 at BC (p < 0.05 vs. SL1/SL2). Four subjects developed AMS, which in one subject later progressed to high altitude pulmonary and cerebral edema. The serum concentration of lipid hydroperoxides (LH) increased markedly at rest and after maximal exercise at BC (p < 0.05 vs. SL1/SL2) whereas no changes were observed for plasma malondialdehyde (MDA). Resting serum total phosphocreatine kinase activity (CPK) and myoglobin also increased at BC (p < 0.05 vs. SL1/SL2) whereas cardiac troponin I (cTnI) remained stable. The resting pain threshold decreased and exercise-induced muscle soreness subsequently increased at BC (p < 0.05 vs. SL1/SL2). An association was observed between resting LH and myoglobin at BC (r = 0.45, p < 0.05) and the increase in LH was related to the increase in exercise-induced muscle soreness at BC (r = 0.96, p < 0.05). Further correlations were identified between the AMS score on day 1 at BC and: a) resting/exercise LH (r = 0.63, p < 0.05/r = 0.51, p < 0.05); and b) resting pain threshold at BC (r = -0.58, p < 0.05). Furthermore, subjects with AMS on day 1 at BC were characterized by a greater decrease in the resting pain threshold and greater increase in resting LH, CPK and myoglobin compared with subjects without AMS (p < 0.05). Headache, fatigue, insomnia and general apathy were the most frequently reported symptoms of AMS.
  
  
  CONCLUSIONS
  Localized free radical-mediated vascular damage of the blood-brain barrier in addition to systemic tissue damage causing overt skeletal muscle soreness may have contributed to the pathophysiology of AMS, the latter through its indirect effects on other non-specific constitutional symptoms such as fatigue and insomnia causing a deterioration in physical performance.
authors.affiliation: Hypoxia Research Unit, University of Glamorgan, Pontypridd, S. Wales, UK. dbailey1@glam.ac.uk
authors.forename: D M
authors.initials: DM
authors.lastname: Bailey
authors.forename: B
authors.initials: B
authors.lastname: Davies
authors.forename: I S
authors.initials: IS
authors.lastname: Young
authors.forename: D A
authors.initials: DA
authors.lastname: Hullin
authors.forename: P S
authors.initials: PS
authors.lastname: Seddon
mesh_terms: D000208:Acute Disease; D000328:Adult; D000532:Altitude Sickness / Q000150:complications / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D016022:Case-Control Studies; D003402:Creatine Kinase / Q000097:blood; D018450:Disease Progression; D005080:Exercise Test; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology*; D009211:Myoglobin / Q000097:blood; D010146:Pain / Q000150:complications / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology*; D010147:Pain Measurement; D012720:Severity of Illness Index; D019210:Troponin I / Q000097:blood
chemical_list: D005609:Free Radicals; D009211:Myoglobin; D019210:Troponin I; D008315:Malondialdehyde; D003402:Creatine Kinase