Muscle structural changes during typical mountaineering expeditions to the Himalayas were assessed by taking muscle biopsies from 14 mountaineers before and after their sojourn at high altitude (greater than 5000 m for over 8 weeks). M. vastus lateralis samples were analyzed morphometrically from electron micrographs. A significant reduction (-10%) of muscle cross-sectional area was found on CT scans of the thigh. Morphologically this loss in muscle mass appeared as a decrease in muscle fiber size mainly due to a loss of myofibrillar proteins. A loss of muscle oxidative capacity was also evident, as indicated by a decrease in the volume of muscle mitochondria (-25%). In contrast, the capillary network was mostly spared from catabolism. It is therefore concluded that oxygen availability to muscle mitochondria after prolonged high-altitude exposure in humans is improved due to an unchanged capillary network, supplying a reduced muscle oxidative capacity.

The oxidative capacity of cat skeletal muscles (soleus, gracilis, and gracilis chronically stimulated for 28 days) was derived from the total mitochondrial content in the muscle, the surface area of mitochondrial inner membranes, and respiratory activities of isolated mitochondria. Mitochondrial content was estimated by standard morphometry. The surface area of mitochondrial inner membranes per unit volume of mitochondria was estimated by a stereological method. The respiratory activities of isolated mitochondria were measured biochemically, using pyruvate/malate, glutamate/malate, succinate, or cytochrome c as substrate. Structurally and functionally, mitochondria from the three muscle types showed nearly identical characteristics. Oxidative activity was dependent on substrate; with succinate, 5.8 ml of 02 per min per ml of mitochondria was the rate most likely to represent physiological conditions. Oxidative activities of 3.1 mlmin'1ml-1 with pyruvate/malate and 14.5 ml min'1-ml-1 with cytochrome c as substrates were theoretical lower and upper bounds. The oxidative capacity ofeach of the three muscles was thus in direct proportion to the total volume of mitochondria in the muscle. The respiratory capacity of isolated mitochondria was very near to the maximal oxygen uptake rate of mitochondria that is commonly estimated in intact muscles of a wide variety of animals.In spite of the pivotal role of mitochondria in oxidative metabolism, their role in determining the oxygen flow through the respiratory system in mammals is still controversial. On the basis of evidence gained from human and animal training studies it is commonly held that mitochondrial oxidative capacity is vastly in excess of the capacity of the cardiovascular system to deliver oxygen (1). The currently most-accepted view is that the cardiovascular system limits maximal oxygen consumption (Vo2 max) during short-term heavy exercise (2) and that an increase in the quantity of mitochondria in muscle tissue with training is important mainly for an improved endurance capacity or fatigue resistance and for substrate selection (3,4).The results of comparative studies using allometric (5) and adaptive variation (6) of Vo2 ma. are in marked contrast to the studies that used exercise training to modify the maximal transport capacity of the respiratory system. The comparative approach demonstrated that among species with severalfold differences in weight-specific Vo2 ma there was a close correlation between Vo2 maxc and whole body mitochondrial content; consequently, the maximal in vivo oxygen consumption of mitochondria covered only a narrow range, 3-5 ml of

This study investigated mechanisms used by horses and steers to increase O2 uptake and delivery (VO2) from resting to maximal rates and identified the mechanisms that enable horses to achieve higher maximal rates of O2 consumption (VO2max) than steers. VO2 and circulatory variables were measured while Standardbred trotting horses and steers (450-kg body mass) stood quietly and ran on a treadmill at speeds up to those eliciting VO2max. As VO2 increased in both species, heart rate and circulating hemoglobin (Hb) concentration increased, thereby increasing O2 delivery by the circulation, while cardiac stroke volume remained unchanged. At VO2max arterial PCO2 increased from its resting value in horses but was unchanged in steers, and arterial PO2 decreased in both species. Although the horses hypoventilated and were hypoxemic at VO2max, no significant decrease in arterial Hb saturation occurred. VO2max of the horses was 2.6 times higher than that of the steers and was associated with a 100% larger cardiac output, 100% larger stroke volume, and 40% higher Hb concentration, whereas heart rates at VO2max were identical in the two species. The higher cardiac output of the horses at VO2max resulted from a 1.2-fold higher mean arterial pressure and 1.6-fold lower peripheral tissue resistance (associated with a larger skeletal muscle capillary bed). Both the magnitude of the difference in VO2max between horses and steers and the mechanisms used to achieve it are the same as observed in smaller pairs of mammalian species with large variation in aerobic capacity.

The aim of the present investigation was to determine, by quantitative electron microscopy, the effects of a 5-wk tail-suspension period on rat soleus muscle ultrastructure. A marked decline (-60%) in muscle mass occurred. The mean fiber cross-sectional area decreased to a greater extent (-75%) than the capillary-to-fiber ratio (-37%), leading to a higher capillary density (+148%) after hypokinesia. The total mitochondrial volume density remained unchanged, whereas the volume density of myofibrils was slightly but significantly reduced (-6%). A shift from subsarcolemmal to interfibrillar mitochondria occurred. Interfibrillar mitochondrial volume density was highest near the fiber border and decreased toward the fiber center. An increase in volume density of satellite cells suggested muscle regenerative events. Soleus atrophy with tail suspension greatly decreases the muscular volume but leaves the ultrastructural composition of muscle fibers relatively unaffected.

Muscle capillaries serve as the final pathway for oxygen and substrate exchange between blood and muscle cells. Intuitively one suspects that the size of the capillary bed should be matched to the metabolic needs of the cells it supplies, implying some optimization between structure and functional demands, and that oxygen should be a dominating factor. Is this concept of an optimal design merely an intellectually appealing idea or can it be supported by evidence?