A potential role for free radical-mediated skeletal muscle soreness in thepathophysiology of acute mountain sickness

Background: it has been suggested that free radicals may be implicated in t he pathophysiology of acute mountain sickness (AMS) due to their ability to initiate and propagate cell membrane damage (3). Therefore, the present st udy was designed to: a) investigate the effects of an expedition to high al titude on metabolic ind ices of free radical-mediated oxidative stress and assess subsequent implications for skeletal/cardiac muscle damage; and b) d etermine 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 a t BC. The trek to BC lasted 20 +/- 5 d. Results: A mild increase in the Lak e 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 t o high altitude pulmonary and cerebral edema. The serum concentration of li pid hydroperoxides (LH) increased markedly at rest and after maximal exerci se 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 ca rdiac troponin I (cTnI) remained stable. The resting pain threshold decreas ed and exercise-induced muscle soreness subsequently increased at BC (p < 0 .05 vs. SL1/SL2). An association was observed between resting LH and myoglo bin at BC (r = 0.45, p < 0.05) and the increase in LH was related to the in crease in exercise-induced muscle soreness at BC (r = 0.96, p<0.05). Furthe r 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) restin g pain threshold at BC (r = -0.58, p < 0.05). Furthermore, subjects with AM S on day 1 at BC were characterized by a greater decrease in the resting pa in threshold and greater increase in resting LH, CPK and myoglobin compared with subjects without AMS (p < 0.05). Headache, fatigue, insomnia and gene ral 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 sorenes s may have contributed to the pathophysiology of AMS, the latter through it s indirect effects on other non-specific constitutional symptoms such as fa tigue and insomnia causing a deterioration in physical performance.