Pathophysiological significance of peroxidative stress, neuronal damage, and membrane permeability in acute mountain sickness.
Free radical-mediated changes in vascular permeability and subsequent inflammatory response may be a contributory pathogenetic cofactor responsible for the development of neurological sequelae associated with acute mountain sickness (AMS). To investigate this, 49 subjects were examined at sea level and serially after rapid ascent to 4,559 m. Although the venous concentration of total creatine phosphokinase activity was measured in all subjects, a complementary examination of lipid peroxidation (F(2)-isoprostanes), inflammatory (TNF-alpha, IL-1beta, IL-2, IL-6, IL-8, C-reactive protein), and cerebrovascular tissue damage (neuron-specific enolase) biomarkers was confined to a subcohort of 24 subjects. A selective increase (P < 0.05) in total creatine phosphokinase was observed in subjects diagnosed with AMS at high altitude (n = 25) compared with apparently healthy controls (n = 24). However, despite a marked increase in IL-6 and C-reactive protein attributable primarily to subjects developing high-altitude pulmonary edema, subcohort analyses demonstrated no selective differences in F(2)-isoprostanes, neuron-specific enolase, or remaining proinflammatory cytokines due to AMS (n = 14). The present findings are the first to demonstrate that free radical-mediated neuronal damage of sufficient degree to be detected in the peripheral circulation does not occur and is, therefore, unlikely to be an important, initiating event that is critical for the development of AMS. The pathophysiological significance of increased sarcolemmal membrane permeability and inflammatory response, either as a cause or epiphenomenon of AMS and/or high-altitude pulmonary edema, remains to be elucidated.
Department of Physiology, University of Glamorgan, Pontypridd, South Wales, UK. dbailey1@glam.ac.uk
Damian M
DM
Bailey
Gian-Reto
GR
Kleger
Manfred
M
Holzgraefe
Peter E
PE
Ballmer
Peter
P
Bärtsch
D000208:Acute Disease; D000532:Altitude Sickness / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D001158:Arteries; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002463:Cell Membrane Permeability; D015331:Cohort Studies; D003402:Creatine Kinase / Q000097:blood; D005740:Gases / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D015227:Lipid Peroxidation; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D018384:Oxidative Stress; D012508:Sarcolemma / Q000378:metabolism*
D015415:Biomarkers; D005740:Gases; D018836:Inflammation Mediators; D015850:Interleukin-6; D002097:C-Reactive Protein; D003402:Creatine Kinase