- 29 - Skeletal Muscle Ultrastructural and Plasma Biochemical Signs of Endothelium Dysfunction Induced by a High-Altitude Expedition (Pumori, 7161m) José Magalhães (1) , António Ascensão (1) , Franklim Marques (2) , José M.C. Soares (1) , Maria J. Neuparth (1) , Rita Ferreira (1) , Francisco Amado (3) and José A. Duarte (1) (1) Department of Sport Biology, Faculty of Sport Sciences, University of Porto, Portugal, (2) Department of Clinical Analysis, Faculty of Pharmacy, University of Porto, Portugal and (3) Department of Chemistry, University of Aveiro, Portugal Abstract The aim of this study was to analyze whether or not a high-altitude expedition to a Himala- yan peak (Pumori, 7161m) induces skeletal muscle ultrastructural and plasma biochemical changes suggestive of microvascular dysfunction. To achieve this purpose 6 mountaineers spent 3 weeks at an altitude range between 5250–7161m after 1 week in an acclimatization trek (2800-5250m). Muscle biopsies from vastus lateralis and blood drawn from antecubi- tal vein were collected at sea level 1 day before and after the expedition to analyze qualita- tive and quantitative (capillary and fiber basement membrane thickness) ultrastructural muscle alterations as well as the plasma activity of tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1). In contrast with a regular skeletal mus- cle pattern observed before the expedition, the post-expedition muscle samples revealed profound structure alterations in the tissue organization. Severe and chronic high altitude exposure also induced significant capillary basement membrane thickness as well as a sig- nificant increase in plasma tPA, PAI-1 and PAI-1/tPA ratio. From the present data it could be concluded that sustained and severe hypobaric-hypoxia exposure constitutes an insult to skeletal muscle with deleterious microvasculature consequences even in acclimatized clim- bers. Key words: basement membrane, fibrinolysis, humans, hypobaric hypoxia, microvascular damage, morphology, oxidative stress. Basic Appl Myol 15 (1): 29-35, 2005 Chronic exposure to extreme high-altitude has been widely considered as a stressful stimuli even to acclima- tized dwellers [35]. In response to this hypobaric hy- poxic condition, several systemic and peripheral physio- logical adaptive responses are acutely and chronically triggered-out to counteract the body overall hypoxic status imposed by environmental oxygen scarceness [35]. Nevertheless, despite the contribution of these or- chestrated mechanisms to diminish the arterial hypoxe- mia and related tissue hypoxia during the course of an acclimatization process, cell oxygen levels at high- altitude seem to be far below the normal sea-level val- ues [37] and thus, even the acclimatized body remains hypoxic compromising tissue redox status homeostasis. In fact, several evidences from chronic high-altitude biological research report cellular disturbances in a va- riety of organs and tissues related, at least in part, to im- paired cellular oxygen tension [35]. Among others, and despite of it extensive plasticity, skeletal muscle may also suffer serious disturbances from a hypoxic envi- ronmental condition, such as the one experienced during high-altitude exposure, which lead to impaired homeo- stasis and disruption in a wide range of cellular func- tions [10]. Indeed, several studies described cumulative evidences of biochemical down-regulation and morpho- logical detrimental effects in skeletal muscle fibers after chronic hypoxia, like enzymes involved in oxidative metabolic pathways, decrease of muscle fibers cross sectional area, decrease mitochondrial volume density, and accumulation of degradation products such as lipo- fuscin-like substances [14]. However, concerning skele- tal muscle microvascular bed, despite the importance of the capillary supply to muscle metabolism and the effect of chronic hypoxia on muscle capillary to fiber structure are well established, there is still a lack of data regard- ing the influence of chronic high-altitude hypoxia on the