Increase In Oxidative Capacity Research Articles

Mitochondrial oxidative capacity and coupling: effects of aging and exercise training

Aging is associated with decreased content and function of mitochondria. Exercise, particularly endurance exercise, stimulates mitochondrial biogenesis, providing an attractive aging countermeasure. The influence of aging and exercise on mitochondrial coupling (i.e., efficiency) is less well studied. We studied the effects of 8 weeks of endurance (ET), resistance (RT), and combined (CT) training on oxidative capacity and coupling in 33 young (Y, 25±1y) and 27 older (O, 70±2y) adults. Mitochondria were isolated from muscle biopsies before and after intervention. State 3 respiration was measured with substrates for complex I, I+II, and II by high-resolution respirometry. Mitochondrial coupling was assessed from respiratory control ratios (RCR) and ADP:O ratios. Before training, respiration was lower in O than Y when expressed per g tissue or mg mito protein. RCR was similar in Y and O, but ADP:O was lower in O. ET and RT groups showed similar, modest increases in oxidative capacity, but the most robust increases were observed in CT in both age groups. Mitochondrial coupling was unaffected by training. These data indicate that 1) aging is associated with reduced mitochondrial capacity at the organelle level, 2) both Y and O exhibit the most profound increase in mitochondrial capacity with combined endurance and resistance training, and 3) age-related declines in mitochondrial coupling are not reversed by exercise.

Myo1c Regulates Glucose Uptake in Mouse Skeletal Muscle

Contraction and insulin promote glucose uptake in skeletal muscle through GLUT4 translocation to cell surface membranes. Although the signaling mechanisms leading to GLUT4 translocation have been extensively studied in muscle, the cellular transport machinery is poorly understood. Myo1c is an actin-based motor protein implicated in GLUT4 translocation in adipocytes; however, the expression profile and role of Myo1c in skeletal muscle have not been investigated. Myo1c protein abundance was higher in more oxidative skeletal muscles and heart. Voluntary wheel exercise (4 weeks, 8.2 ± 0.8 km/day), which increased the oxidative profile of the triceps muscle, significantly increased Myo1c protein levels by ∼2-fold versus sedentary controls. In contrast, high fat feeding (9 weeks, 60% fat) significantly reduced Myo1c by 17% in tibialis anterior muscle. To study Myo1c regulation of glucose uptake, we expressed wild-type Myo1c or Myo1c mutated at the ATPase catalytic site (K111A-Myo1c) in mouse tibialis anterior muscles in vivo and assessed glucose uptake in vivo in the basal state, in response to 15 min of in situ contraction, and 15 min following maximal insulin injection (16.6 units/kg of body weight). Expression of wild-type Myo1c or K111A-Myo1c had no effect on basal glucose uptake. However, expression of wild-type Myo1c significantly increased contraction- and insulin-stimulated glucose uptake, whereas expression of K111A-Myo1c decreased both contraction-stimulated and insulin-stimulated glucose uptake. Neither wild-type nor K111A-Myo1c expression altered GLUT4 expression, and neither affected contraction- or insulin-stimulated signaling proteins. Myo1c is a novel mediator of both insulin-stimulated and contraction-stimulated glucose uptake in skeletal muscle.

Short-term endurance training does not alter the oxidative capacity of human subcutaneous adipose tissue

Endurance training results in adaptations that enhance regulation of energy storage and expenditure at rest and during exercise. While processes involved in skeletal muscle oxidative remodelling are well described, it is unknown whether oxidative capacity of human subcutaneous white adipose tissue (WAT) is modified by endurance training. Since human WAT retains rudimentary characteristics required for upregulation of oxidative function, we hypothesised that 10 days of intense endurance training would promote changes in WAT that favour an increase in oxidative capacity. Eleven untrained males (age 22 +/- 1 years, body mass 81 +/- 5 kg, peak oxygen uptake (VO(2peak)) 3.7 +/- 0.2 l/min) undertook a 10-day endurance training protocol. Subcutaneous adipose tissue biopsies were taken from the abdomen prior to and 1 day after completion of training and analysed for fatty acid oxidative capacity, citrate synthase activity, and mitochondrial content via electron microscopy and gene expression analyses. There was a reduction in whole-body rates of carbohydrate oxidation, and concomitant increases in fat oxidation rate measured during 20-min of submaximal cycling (70% of pre-training VO(2peak)) and an increase in basal GLUT4 protein in skeletal muscle. Despite these training-induced adaptations, there were no changes in WAT of ex-vivo fat oxidation rate, maximal citrate synthase activity, mitochondrial volume or in selected genes involved in adipose tissue oxidative capacity. We conclude that 10 days training in previously untrained subjects results in adaptations in skeletal muscle but does not increase the oxidative capacity of WAT.

Hyaluronan: is it a biomarker for adipose development within bovine muscle?

Based on an association with extracellular matrix remodelling, mitosis, proliferation and adipogenic differentiation, the glycosaminoglycan hyaluronan (HA) was assessed as a marker for intramuscular fat (IMF) development (marbling) in bovine loin muscle (longissimus dorsi, LD). Loin samples collected from the quartering site of feedlot-finished Wagyu–Angus and Jersey–Limousin steers were assayed for percentage IMF (IMF%) and HA after assignment of AUS-MEAT marbling scores. There was a moderate phenotypic correlation (r2 = 0.69) between IMF% and marbling score but little variance was explained by HA concentration. Breed was not a significant factor in marbling score or IMF% but did influence the HA concentration of the LD, with Wagyu–Angus steers having 2-fold more HA than Jersey–Limousin steers at the same marbling score. The non-linear decline in fat-adjusted HA levels as marbling score increased suggests that HA concentration was associated with lean growth potential of the muscle rather than adipogenesis. Using a different experimental approach, differences in distribution and amount of HA could not be discerned in histological sections of LD from age-matched Wagyu–Hereford heifers allocated to a low (score 1) or medium (score 3) marbling score group. These findings were consistent with the absence of differences between the two groups for other indicators of fatness (IMF% and P8 fat depth), maturity and myofibre characteristics despite an increase in oxidative capacity of the muscle with age. The data support the conclusion that the concentration of HA in the LD alone was not predictive of development of intramuscular fat.

Enhancement of Muscle Mitochondrial Oxidative Capacity and Alterations in Insulin Action Are Lipid Species Dependent

OBJECTIVEMedium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-chain fatty acids (LCFAs); however, relatively little is known regarding their effect on insulin action. Here, we examined the tissue-specific effects of MCFAs on lipid metabolism and insulin action.RESEARCH DESIGN AND METHODSC57BL6/J mice and Wistar rats were fed either a low-fat control diet or high-fat diets rich in MCFAs or LCFAs for 4–5 weeks, and markers of mitochondrial oxidative capacity, lipid levels, and insulin action were measured.RESULTSMice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%, P < 0.01) but remained at low-fat diet control levels in the MCFA-fed animals. The LCFA diet increased (20–50%, P < 0.05) markers of mitochondrial metabolism in muscle compared with low-fat diet–fed controls; however; the increase in oxidative capacity was substantially greater in MCFA-fed animals (50–140% versus low-fat–fed controls, P < 0.01). The MCFA diet induced a greater accumulation of liver triglycerides than the LCFA diet, likely due to an upregulation of several lipogenic enzymes. In rats, isocaloric feeding of MCFA or LCFA high-fat diets induced hepatic insulin resistance to a similar degree; however, insulin action was preserved at the level of low-fat diet–fed controls in muscle and adipose from MCFA-fed animals.CONCLUSIONSMCFAs reduce adiposity and preserve insulin action in muscle and adipose, despite inducing steatosis and insulin resistance in the liver. Dietary supplementation with MCFAs may therefore be beneficial for preventing obesity and peripheral insulin resistance.

Temporal and spatial patterns of gene expression in skeletal muscles in response to swim training in adult zebrafish (Danio rerio)

In adult zebrafish, 4 weeks of exercise training is known to induce an increase in mitochondrial enzymes such as citrate synthase (CS) when determined in mixed (red and white) muscle. However, this remodeling is not accompanied by changes in PGC-1alpha mRNA, a potent inducer of mitochondrial biogenesis in mammals. To further understand this response, we examined absolute and relative changes in red muscle area by histochemistry after 4 weeks of swim training. We also examined fiber-type specific responses in the expression of metabolic genes and putative regulators in red and white muscle of adult zebrafish at 1 and 8 weeks of training and in recovery from a single bout of exercise. Total red muscle area was unaltered after 4 weeks of training. The mRNA expression of CS was unaffected in red muscle, while it was increased in white muscle after 1 week of training and remained elevated at 8 weeks of training, suggesting an increase in oxidative capacity of this fiber type. In contrast, PGC-1alpha mRNA was elevated in both muscles only after 1 week of training. In both muscles, an acute bout of exercise rapidly (within 0-2 h post-exercise) induced PGC-1alpha mRNA and a delayed (24 h) increase in CS mRNA post-exercise. These results suggest complex temporal and spatial adaptive molecular responses to exercise in the skeletal muscles of zebrafish.

Increased susceptibility to oxidative damage in post-diabetic human myotubes

Obesity is an important risk factor for the development of type 2 diabetes, but not all obese individuals develop this complication. The clinical signs of type 2 diabetes can often be reversed with weight loss; however, it is unknown whether the skeletal muscle oxidative stress associated with type 2 diabetes remains after weight loss. We hypothesised that chronic exposure to high glucose and insulin would re-elicit impaired metabolism in primary myotubes from patients with a history of type 2 diabetes. Obese participants with or without type 2 diabetes completed a standardised weight loss protocol, following which all participants were euglycaemic and had similar indices of insulin sensitivity. Satellite cells were isolated from muscle biopsies and differentiated under low or high glucose and insulin conditions (HGI). Cells from participants with no history of type 2 diabetes showed robust increases in mitochondrial content, citrate synthase and cytochrome c oxidase activities when exposed to HGI. This increase in oxidative capacity was absent in cells from patients with a history of type 2 diabetes. High glucose and insulin caused increased oxidative damage in cells from the latter, despite higher superoxide dismutase expression. Cells from patients with a history of type 2 diabetes were unable to decrease mitochondrial membrane potential in response to HGI, potentially due to lower levels of uncoupling protein-3. This is the first report to note that primary myotubes from patients with a history of type 2 diabetes are unable to adapt to a hyperglycaemic-hyperinsulinaemic challenge. We have demonstrated that impaired mitochondrial biogenesis and an inability to manage oxidative stress define a muscle phenotype at risk of obesity-associated type 2 diabetes.

MitoNEET dimerization uncouples mitochondria and reduces oxidative stress

MitoNEET is a novel mitochondrial membrane protein that contains a 2Fe‐2S center and may be involved in regulating redox reactions. The goal of these studies was to determine if mitoNEET dimerization uncouples mitochondrial respiration and thereby reduces oxidative stress (ROS). A cell line, Swiss 3T3 cells, that does not express mitoNEET was transfected with mitoNEET cDNA and clonal lines established. In the absence of oxidative stress mitoNEET is a monomer, mitochondrial ROSs were low, and oxidative capacity was low. In the presence of exogenous oxidative stress such as hydrogen peroxide and peroxynitrate, mitoNEET dimerized, mitochondrial ROSs were high, and oxidative capacity was increased. Endogenously induced oxidative stress was generated by incubating the cells in high glucose (20 mM) or high fatty acids (0.5 mM). The cells responded similarly to endogenous oxidative stress as they did with exogenous oxidative stress. In contrast, cells that were not expressing mitoNEET underwent apoptosis when identical levels of oxidative stress were employed. Time course studies demonstrated that mitoNEET dimerized as ROS levels increased. This correlated with an increase in oxidative capacity and mitochondrial uncoupling. MitoNEET returned to a monomer as ROS levels decreased. These data suggest that the dimerization of mitoNEET plays a role in limiting mitochondrial ROS levels and cell apoptosis.

B011 Stimulus specific changes of energy metabolism in hypertrophied heart

Cardiac energy metabolism is a determinant of the response to hypertrophic stimuli. We investigated how energy metabolism responds to physiological or pathological stimuli leading to comparable levels of hypertrophy. We compared the cardiac energetic status in models of hypertrophy induced by physiological stimuli like pregnancy (18-19 days of gestation) or exercise training (8-weeks treadmill) and by hypertension (spontaneously hypertensive rats, SHR) in 15 weeks-old female rats, all leading to a 10 % cardiac hypertrophy. Late stage of compensated hypertrophy was also studied in 25 weeks-old SHR (35 % of hypertrophy) Markers of cardiac remodelling did not follow a unique pattern of expression: in trained rats, only atrial natriuretic factor was increased and in gravid rats, calcineurin activation was reduced while β-MHC expression was enhanced. All these markers were clearly up-regulated in 25 weeks-old SHR. Respiration of permeabilized cardiac fibers revealed a 17 % increase in oxidative capacity in trained rats only. Citrate synthase, complex I or cytochrome oxidase activity, and expression of the master regulator of mitochondrial biogenesis, PGC-1α, were not changed suggesting that compensated hypertrophy does not involve mitochondrial biogenesis alterations. Mitochondrial fatty acid utilization tended to increase in trained rats and decreased by 14 % in early SHR. No change in PPARα expression but significant decrease in MCAD and CPTI expression were observed in pregnancy, while these 3 markers of β-oxidation were up-regulated after training. Taken together these results show that there is not an univocal pattern of cardiac adaptations in response to physiological or pathological hypertrophic stimuli but that rather the pattern, intensity and nature of the stimuli play an important role in determining adaptation of energy metabolism to increased workload.

Stimulus specific changes of energy metabolism in hypertrophied heart

Cardiac energy metabolism is a determinant of the response to hypertrophic stimuli. To investigate how it responds to physiological or pathological stimuli, we compared the energetic status in models of hypertrophy induced by physiological stimuli (pregnancy or treadmill running) and by pathological stimulus (spontaneously hypertensive rats, SHR) in 15 week-old female rats, leading to a 10% cardiac hypertrophy. Late stage of compensated hypertrophy was also studied in 25 week-old SHR (35% of hypertrophy). Markers of cardiac remodelling did not follow a unique pattern of expression: in trained rats, only ANF was increased; in gravid rats, calcineurin activation and BNP expression were reduced while β-MHC expression was enhanced; all markers were clearly up-regulated in 25 week-old SHR. Respiration of permeabilized fibers revealed a 17% increase in oxidative capacity in trained rats only. Mitochondrial enzyme activities, expression of the master regulator PGC-1α and mitochondrial transcription factor A, and content of mitochondrial DNA were not consistently changed, suggesting that compensated hypertrophy does not involve alterations of mitochondrial biogenesis. Mitochondrial fatty acid utilization tended to increase in trained rats and decreased by 14% in 15 week-old SHR. Expression of markers of lipid oxidation, PPARα and its down-stream targets MCAD and CPTI, was up-regulated after training and tended to decrease in gravid and 15 week-old SHR rats. Taken together these results show that there is no univocal pattern of cardiac adaptation in response to physiological or pathological hypertrophic stimuli, suggesting that other factors could play a role in determining adaptation of energy metabolism to increased workload.

Highlights From The Literature

Highlights From The Literature

Metabolic responses of muscle to exercise

AbstractMuscle is a tissue with a great plasticity due to the fact that it is composed of fibres having different contractile and metabolic properties. In horses, muscle metabolic responses to exercise are studied by taking biopsies from the gluteus medius muscle. Histochemical stains are used to identify slow contracting type I fibres and fast contracting type IIA and type IIB fibres and to evaluate fibre areas, capillary supply, oxidative capacity, glycogen and lipid content in a muscle. Biochemical analyses of substrates, metabolites and enzyme activities are performed either on a whole piece of muscle, on pools of fibres or on single fibres of identified type.All fibres contain glycogen whereas lipid is mainly found in type I and type IIA fibres that have smaller cross–sectional areas and a higher oxidative capacity than type IIB fibres. Large variations can be seen in metabolic profile between and within fibre types. The most common muscular adaptation to training is an increase in oxidative capacity, capillary density and an increase in the type IIA/IIB ratio. The order of recruitment of fibres during most types of exercise is from type I to type IIA and type IIB.The higher the intensity of exercise, the faster is the breakdown of glycogen. After racing (1640-2640m), and after high intense treadmill exercise, concentrations of lactate and inosine monophosphate (IMP) are increased in the muscle and concentrations of glycogen, adenosine triphosphate (ATP) and creatine phosphate (CP) decreased. Extremely low ATP and high IMP concentrations especially in some type II fibres are observed after racing.After exercise of low intensity and long duration glycogen and triglyceride stores in muscle are utilised, amino acid metabolism is enhanced and protein degradation may occur. After submaximal treadmill exercise to fatigue and after endurance rides glycogen is degraded and depletion occurs mainly in type I and type IIA fibres.Fibre type composition, substrate sources and differences in metabolic properties among fibres and the extent to which fibres are recruited are all factors that influence the metabolic responses of muscle to exercise. Biochemical analyses on whole muscle must be interpreted with caution since large variations in metabolic response to exercise occur among different fibres.

Cold-induced hyperthyroidism produces oxidative damage in rat tissues and increases susceptibility to oxidants

In this work, we investigated whether cold exposure-induced hyperthyroidism increases oxidative damage and susceptibility to oxidants of rat liver, heart and skeletal muscle. All tissues exhibited gradual increases in hydroperoxide and protein-bound carbonyl levels. Glutathione peroxidase activity increased in all tissues after 2 days and further increased in the muscle after 10 days of cold exposure. Liver glutathione reductase activity increased after 10 days of cold exposure, while heart and muscle activities were not modified. Vitamin E levels were not affected by cold, while coenzyme Q9 and coenzyme Q10 levels decreased in heart and muscle after 2-day cold exposure and were not further modified after 10 days. Liver coenzyme Q9 levels increased after 2 days whereas coenzyme Q10 levels increased after 10 days in the cold. The whole antioxidant capacity was lowered, while parameters positively correlated with susceptibility to oxidants were increased by cold. Lipid fatty acid composition was modified in all tissues. In particular, fatty acid unsaturation degree increased in heart and muscle. Cytochrome oxidase activity increased, suggesting an increased content of hemoproteins, which are able to generate OH radical. This view was supported by the observation that the tissue susceptibility to H 2O 2 treatment, which is strongly correlated to iron–ligand content, increased after cold exposure. In this frame, it is apparent that the increase in oxidative capacity, necessary for homeotherm survival in low temperature environments, has potential harmful effects, because it results in increased susceptibility to oxidative challenge.

Acyl-coenzyme A binding protein expression is fibre-type specific in rat skeletal muscle but not affected by moderate endurance training.

The metabolic active form of free fatty acids, long-chain acyl-coenzyme A (lc-acyl-CoA), binds to its 10-kDa binding protein with high affinity. In the present study, we investigated the content of lc-acyl-CoA binding protein (ACBP) in different skeletal muscle fibre types. Soleus had the highest expression of ACBP (0.33+/-0.02 microg mg protein(-1)) and the content was as high as in heart muscle. The content in mixed gastrocnemius (0.27+/-0.02 microg mg protein(-1)), extensor digitorum longus (0.21+/-0.01 microg mg protein(-1)) and white gastrocnemius (0.16+/-0.01 microg mg protein(-1)) were lower than in soleus and differed from each other ( P<0.05). The ACBP content correlated positively with the fraction of myosin heavy chain I in the skeletal muscles (Spearman rank correlation rho=0.90; P<0.0001), and negatively with the myosin heavy chain IIB fraction ( rho=-0.92; P<0.0001). The content of ACBP also correlated with 3-hydroxy-acyl-CoA dehydrogenase (HAD) and citrate synthase (CS). Five weeks of endurance training increased HAD and CS activities in soleus and mixed gastrocnemius but did not affect the ACBP content. These findings demonstrate that ACBP expression is fibre-type specific in skeletal muscles and correlates with beta-oxidative potential. Training-induced increase in oxidative capacity was not paralleled by an increase in ACBP content.

Effects of body size on biochemical characteristics of trabecular cardiac muscle and plasma of rainbow trout ( Oncorhynchus mykiss)

The objective of this study was to characterize biochemical indices of oxidative metabolism in trabecular cardiac muscle of female rainbow trout over a 200-fold size range. We also examined scaling effects on plasma concentrations of protein, albumin, and non-esterified fatty acids (NEFA). Animals were sampled from four size categories (<20 g, 100–200 g, 300–400 g and >2 kg). Ventricle mass relative to body mass was size-dependent, with the smallest trout having smaller hearts. Total protein in cardiac tissue was 20% higher in animals weighing over 300 g compared to fish less than 200 g. Plasma albumin and protein were increased 50–70% in trout over 100 g compared to fish smaller than 20 g. NEFA in plasma were similar for all animals. Activities of carnitine palmitoyltransferase and cytochrome oxidase were elevated 53% and 38%, respectively, in trabecular cardiac muscle of the largest trout compared to the smallest animals. Citrate synthase activity was independent of heart size, suggesting that the increase in oxidative capacity was not due to an increase in mitochondrial density. The increased capacity to bind and transport fatty acids in blood and the higher oxidative capacity of cardiac muscle may reflect a metabolic adaptation for increased oxidation of fatty acids and ventricular performance in larger female trout. These findings are not consistent with the scaling paradigm of oxidative metabolism and may reflect changes in ventricular architecture with ontogeny.

Increase in oxidative capacity of pigeon pectoralis muscle before and after fledging

Using the pectoralis muscle of the pigeon (Columba livia), we previously showed that at fledging, both fast-twitch oxidative-glycolytic (FOG) and fast-twitch glycolytic (FG) fiber types retain a myosin isoform characteristic of the neonatal period, despite the birds being at adult body mass. Our aim here was to test the hypothesis that muscle fibers of the pigeon pectoralis increase their aerobic capacity both before and after fledging. Pigeons aged from 1 week after hatching through to adulthood were used. Adopting a microdensitometric technique from studies on mammalian muscle, the activity of succinate dehydrogenase (SDH) within individual fibers was quantified as optical density and used as an index of aerobic capacity. We demonstrate a strong linear correlation (r2 = 0.936) between optical density of FOG fibers and time exposed to the SDH incubation medium. Optical density of FG fibers, however, could not be discerned from background staining. SDH activity in FOG fibers increased logarithmically (r2 = 0.969) with the age of the birds, increasing 2.5-fold from 1 week through to adult. Thus, aerobic capacity did increase both before and after fledging. In addition, within FOG fibers, aerobic capacity and myosin content appear to have different timetables of development.

Exercise training enhances adrenergic constriction and dilation in the rat spinotrapezius muscle.

Treadmill training increases functional vasodilation in the rat spinotrapezius muscle, although there is no acute increase in blood flow and no increase in oxidative capacity. To assess concurrent changes in vascular reactivity, we measured arterial diameters in the spinotrapezius muscle of sedentary (Sed) and treadmill-trained (Tr; 9-10 wk; terminal intensity 30 m/min, 1.5 degrees incline, for 90 min) rats during iontophoretic application of norepinephrine, epinephrine (Epi), and H+ (HCl) and during superfusion with adenosine. Terminal-feed arteries and first-order arterioles in Tr rats constricted more than those in Sed rats at the higher current doses of norepinephrine and Epi. In contrast, at low-current doses of Epi, first- and second-order arterioles dilated in Tr but not in Sed rats. The vascular responses to HCl were highly variable, but second-order arterioles of Tr rats constricted more than those of Sed rats at intermediate-current doses. There were no significant differences between Sed and Tr rats in the vascular responses to adenosine. Both adrenergic vasodilation and vasoconstriction were enhanced in the spinotrapezius muscle of Tr rats, and enhanced adrenergic vasodilation may contribute to increased functional vasodilation. These observations further demonstrate vascular adaptations in "nontrained" skeletal muscle tissues.

Increase in oxidative capacity of pigeon pectoralis muscle before and after fledging

Increase in oxidative capacity of pigeon pectoralis muscle before and after fledging

Femoral artery ligation stimulates capillary growth and limits training-induced increases in oxidative capacity in rats.

The purpose of this study was to assess the interaction of arterial insufficiency and exercise training on soleus and plantaris muscle capillarity and oxidative capacity in adult rats. Arterial insufficiency was created by ligation (LIG) of the right femoral artery, and exercise training (TR) was performed on a rodent treadmill. The left hindlimb served as a normally (NORM) perfused control. Capillary:fiber ratio number of capillary contacts per fiber, and citrate synthase activity (CS) were evaluated in the plantaris (Plant) and soleus (Sol) muscles. In sedentary rats, CS was similar between LIG and NORM (Plant: 24.4 vs. 24.3 mumol.min-1.g-1; Sol: 16.6 vs. 16.9 mumol.min-1.g-1), but capillaries per fiber and capillary contacts per fiber were significantly elevated in the plantaris muscle of LIG (2.46 vs. 2.10 caps/fiber, 5.78 vs. 5.03 capillary contacts). CS was elevated in both limbs of TR but was lower in LIG than in NORM (Plant: 28.5 vs. 32.4 mumol.min-1.g-1; Sol: 21.1 vs. 24.9 mumol.min-1.g-1). Treadmill training did not significantly affect capillarity in NORM. However, muscles in the ligated limb of TR tended to have greater capillarity than comparable muscles in either NORM of TR of LIG in SED. These results demonstrate capillary proliferation in the plantaris but not soleus muscle of rat hindlimbs with femoral artery ligation. Capillarity and CS adaptations were not obligatorily related in LIG, and femoral artery ligation and exercise training appeared to have interactive effects on skeletal muscle capillarity.

SKELETAL MUSCLE RESPONSES OF TWO ???COMPLETE??? PARAPLEGICS TO LEG CYCLE TRAINING 232

The purpose of this research was to identify changes in skeletal muscle in“complete” paraplegics following leg cycle training. One male (47 yr, 1 yr post-injury) and one female (24 yr, 4.2 yr post-injury) with complete loss of sensory and voluntary motor control below the T2 and T11 levels (ASIA class A), respectively, participated in the study. After 2 learning sessions on an energy-storage ergometer (Psycle®), subjects could pedal voluntarily. Each subject performed continuous leg cycle exercise 30 to 95 min, 3 dy/wk. Muscle biopsies were obtained from the vastus lateralis prior to and following 12 weeks of training. Leg cycling power improved 202% from 4.3 to 13 W for the male and 5.6 to 8.8 W for the female. Percentage type I and type II muscle fibers decreased from 26% to 19% and increased from 74% to 81%, respectively, in the male and increased from 5% to 8% and decreased from 95% to 92%, respectively, in the female. Type I and II fiber cross sectional areas decreased 45% from 4533 to 2518 μm2 and decreased 29% from 5119 to 3652 μm2, respectively, for the male and increased 78% from 2286 to 4078 μm2 and increased 111% from 1136 to 2400 μm2, respectively, for the female. However, type IIa fiber cross sectional area increased 57% in the male and 15% in the female. Cytochrome c oxidase activity increased 8% from 18.2 to 19.6 μmol·min-1 g protein-1 in the male and 30% from 15.2 to 19.7 μmol·min-1·g protein-1 in the female. These findings suggest that leg skeletal muscles of “complete” paraplegics may undergo selective hypertrophy and an increase in oxidative capacity in response to low power leg cycle training.