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Am J Physiol Heart Circ Physiol 297: H364-H374, 2009. First published May 8, 2009; doi:10.1152/ajpheart.00272.2009
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Region-specific adaptations in determinants of rat skeletal muscle oxygenation to chronic hypoxia

R. C. I. Wüst,1,2 R. T. Jaspers,2 A. F. van Heijst,3 M. T. E. Hopman,4 L. J. C. Hoofd,4 W. J. van der Laarse,5 and H. Degens1

1Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester; 2Research Institute MOVE, Faculty of Human Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam; 3Department of Pediatrics and 4Department of Physiology, Radboud University Nijmegen Medical Centre, Nijmegen; and 5Department of Physiology, Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands

Submitted 19 March 2009 ; accepted in final form 28 April 2009

Chronic exposure to hypoxia is associated with muscle atrophy (i.e., a reduction in muscle fiber cross-sectional area), reduced oxidative capacity, and capillary growth. It is controversial whether these changes are muscle and fiber type specific. We hypothesized that different regions of the same muscle would also respond differently to chronic hypoxia. To investigate this, we compared the deep (oxidative) and superficial (glycolytic) region of the plantaris muscle of eight male rats exposed to 4 wk of hypobaric hypoxia (410 mmHg, PO2: 11.5 kPa) with those of nine normoxic rats. Hematocrit was higher in chronic hypoxic than control rats (59% vs. 50%, P < 0.001). Using histochemistry, we observed 10% fiber atrophy (P < 0.05) in both regions of the muscle but no shift in the fiber type composition and myoglobin concentration of the fibers. In hypoxic rats, succinate dehydrogenase (SDH) activity was elevated in fibers of each type in the superficial region (25%, P < 0.05) but not in the deep region, whereas in the deep region but not the superficial region the number of capillaries supplying a fiber was elevated (14%, P < 0.05). Model calculations showed that the region-specific alterations in fiber size, SDH activity, and capillary supply to a fiber prevented the occurrence of anoxic areas in the deep region but not in the superficial region. Inclusion of reported acclimatization-induced increases in mean capillary oxygen pressure attenuated the development of anoxic tissue areas in the superficial region of the muscle. We conclude that the determinants of tissue oxygenation show region-specific adaptations, resulting in a marked differential effect on tissue PO2.

tissue oxygenation; capillarization; oxidative capacity



Address for reprint requests and other correspondence: R. Wüst, Institute of Membrane and Systems Biology, Faculty of Biological Sciences, Univ. of Leeds, Worsley Bldg., Leeds LS2 9JT, UK (e-mail: r.wust{at}leeds.ac.uk)







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