PubMed Health⌕ Search

Biomedical subjects

A Elander

Publications and source records attributed to A Elander.

28 records · Page 2Linked to original sources

Leg exchange of amino acids during exercise in patients with arterial insufficiency.

Intermittent claudication is associated with adaptation in muscle metabolism. This study has evaluated the metabolism of amino acids at rest and during non-steady state exercise in patients with arterial insufficiency of at least six months duration in comparison with matched control individuals. The exchange of amino acids were measured during two periods of acute exercise; one initial exercise period with a standardized work load and exercise time and a second exercise period which continued until further exercise was impossible due to pain in the patients and exhaustion in the controls. The maximum blood flow was reduced by 40% in the patients but the maximum oxygen uptake per unit power developed was almost the same in patients and controls. The patients had significantly lower concentrations of glutamine, lysine and taurine at rest compared with the controls. The exchange of amino acids across the resting leg did not differ between the two groups. Exercise increased the efflux of amino acids in both patients and controls. The efflux of glutamine (896 +/- 205 vs. 48 +/- 359 nmol/100 ml/min/watt) was higher in the patients compared to the controls at the first exercise period with inverse changes in the opposite direction of asparagine (149 +/- 105 vs. 799 +/- 121 and 27 +/- 70 vs. 633 +/- 334 nmol/100 ml/min/watt at the first and second exercise, respectively. Alanine release did not differ between the groups. The complementary patterns of glutamine and asparagine during hypoxic exercise in the patients may reflect the fact that these amino acids share a common carrier system. The similarity in the efflux of non-metabolized amino acids, such as methionine, phenylalanine, tyrosine and 3-methylhistidine, indicated that muscle hypoxia in claudication patients did not promote net degradation of either globular or myofibrillar proteins, although exercise increased the efflux of 3-methylhistidine three- to fourfold in both patients and control individuals (from 1 +/- 0.4 to 4 +/- 1.8 and from 0 +/- 0.7 to 6 +/- 2.5 nmol/100 ml/min/watt, respectively). The exercise-induced alterations in leg exchange of amino acids were restored within 10-20 min following exercise regardless of hypoxia. The results demonstrate that patients with arterial insufficiency have altered intermediary metabolism of amino acids during exercise. However, muscle hypoxia in such patients does not seem to promote a negative protein balance or induce serious alterations in cell membrane integrity.

Aged↗

Substrate exchange in human limb muscle during exercise at reduced blood flow.

The substrate exchange of the calf muscles during leg exercise was compared in patients with chronically reduced blood flow and in matched controls. The arteriovenous differences of glucose, lactate, pyruvate, free fatty acids, glycerol, acetoacetate, beta-OH-butyrate, oxygen, and carbon dioxide were analyzed at rest, at the end of two exercise periods at various work loads, and after 10 min of recovery. Calf blood flow was measured with an electrocardiogram-triggered, computerized, strain gauge, venous occlusion plethysmograph. The results indicate that there was increased extraction of oxygen and ketone bodies in patients with reduced blood flow during exercise, whereas the glucose extraction tended to be lower than in controls. The leg respiratory quotient was lower in the patients even at the point of claudicating pain, suggesting oxidation of endogenous fat. The simultaneously elevated lactate release can be explained by local hypoxia in some muscle fiber populations. The findings are discussed in relation to the enzymatic adaptations known to occur in the calf muscle tissue of these patients.

3-Hydroxybutyric Acid↗

Influence of endurance training on glucose transport and uptake in rat skeletal muscle.

The paired tracer-dilution method applied to the rat hindlimb perfusion technique was used to investigate the effect of a 10-wk treadmill training program on glucose transport and net uptake in rat skeletal muscles. Glycolytic and oxidative marker enzyme activities were determined. The rats were allowed to rest for 2 days before the experiments were carried out, since long-term adaptive changes were to be studied. The endurance training program caused a 30% increase in the 3-hydroxyacyl-CoA dehydrogenase and citrate synthase activities, but no changes in glycolytic enzymes, confirming that endurance training provokes an increase in the oxidative capacity of the muscle. No significant differences were found in glucose transport rate or net glucose uptake between trained and sedentary rats, which indicates that no long-term adaptive changes in glucose utilization occur in response to endurance training.

Animals↗

Biochemical and morphometric properties of mitochondrial populations in human muscle fibres.

Two mitochondrial subpopulations were evaluated with biochemical and morphological techniques in human gastrocnemius muscle of 10 patients with peripheral arterial insufficiency and 12 control individuals. The subsarcolemmal mitochondria were released by gentle homogenization, with a recovery of 32-37%, and the intermyofibrillar by enzymic digestion and further mechanical disintegration, recovery 18-21%. The subsarcolemmal mitochondria were morphologically defined as those located within 2 micron from the sarcolemma membrane and the intermyofibrillar mitochondria as those located in the rest of the fibre. In the controls the intermyofibrillar mitochondria had a lower respiratory ratio than the subsarcolemmal, owing to a higher state II respiration. The subsarcolemmal space, which contained 25% of the mitochondria, had a mitochondrial volume density two- to three-fold that of the intermyofibrillar space in the controls. The patients, who had a 48-64% higher oxidative enzyme capacity in their muscle tissue, had higher respiratory rate and respiratory control index with similar ADP/O ratio in the subsarcolemmal fraction in comparison with the controls. The citrate synthase activity was higher in both mitochondrial fractions of the patients. The volume densities of mitochondria, total as well as for both subpopulations, were also higher in the patients, which was further reflected in higher yields of mitochondrial protein. The results demonstrate that both subpopulations of muscle mitochondria are able to adapt quantitatively and/or qualitatively. Furthermore, they show that the increased oxidative enzyme capacity of the patients is associated with an increased quantity of both mitochondrial populations and a qualitative improvement of the respiratory activity of the subsarcolemmal mitochondria.

3-Hydroxyacyl CoA Dehydrogenases↗

Metabolic adaptation to reduced muscle blood flow. I. Enzyme and metabolite alterations.

A rat model was developed in which the adaptive effects of exposing skeletal muscle tissue to a reduced blood flow during muscle contractions could be studied. The common iliac artery was ligated in one hindlimb, using the other as control. This procedure reduced the exercise blood flow to the individual muscles of the lower limb by 76-93%, evaluated with the microsphere technique. Muscle contractions were induced by electrical stimulation of the sciatic nerves in both legs. After intermittent stimulation for 6 days, a significant increase in citrate synthase and cytochrome c oxidase activities was found in the soleus (26%) and extensor digitorum longus (EDL, 20%) muscles of the ligated legs compared with the control legs. Resting metabolite concentrations were also measured, and a reduction of the ATP level (soleus 35%, EDL 14%) and an increased glycogen content (55-71%) were found. These results demonstrate that a reduced blood flow during muscle contractions provokes an adaptive increase of the oxidative enzyme capacity as well as altered resting levels of intracellular metabolites.

Adaptation, Physiological↗

Metabolic adaptation to reduced muscle blood flow. II. Mechanisms and beneficial effects.

Increased mitochondrial enzyme activities are induced in rat muscles after common iliac artery ligation, giving a 76-93% blood flow reduction, and 6 days of intermittent muscle stimulation. To elucidate the trigger for this enzyme induction, the acute alterations in the metabolite pattern during contractions were evaluated. More pronounced changes in intramuscular PO2, creatine phosphate, ATP/ADP, lactate/pyruvate, and glycogen were observed in the ligated leg. The benefit of this enzyme alteration was investigated with the hindlimb perfusion technique. Enzymatically adapted and control legs were perfused at reduced flow during contractions. Similar oxygen consumption and glucose uptake but a significantly lower lactate release were observed in the adapted legs. A lower lactate level, lactate/pyruvate, and a better maintained creatine phosphate/creatine were found in the adapted soleus muscle. The results demonstrate that the increase of mitochondrial enzymes is preceded by acute alterations in energy metabolites due to intermittent hypoxia during contractions at reduced flow and that this enzyme adaptation allows the muscle tissue to maintain a lower anaerobic metabolism and a better energy state during exercise.

Adaptation, Physiological↗

Peripheral vascular disease.

Human as well as experimental studies were performed to evaluate the effects of reduced blood flow on skeletal muscle metabolism. Claudicating patients had a lower oxygen tension and energy state in the gastrocnemius muscle in relation to the work performed during leg exercise, as compared to normal subjects. At a certain oxygen tension, however, the patients were able to maintain a lower [lactate]/[pyruvate] ratio in the muscle tissue, which was ascribed to their higher capacity for oxidative metabolism. Perfusing the contracting rat hindlimb at reduced blood flow showed more pronounced changes in the energy and redox-state in the gastrocnemius muscle than in the soleus muscle. This shows that a muscle composed of fast glycolytic fibers is more susceptible to a reduced flow during exercise than one composed of slow oxidative fibers and suggests that the claudicating pain is located in the former. Repeated exposure of rat muscles to reduced blood flow during exercise caused chronic changes in oxidative enzyme activities, in line with the adaptive changes found in claudicating patients.

Aged↗

Optimal conditions for assay of cytochrome-c-oxidase activity in human skeletal muscle tissue.

Conditions for the assay of cytochrome-c-oxidase in human skeletal muscle tissue were studied, including an evaluation of the optimal conditions during the in vitro assay as well as the optimal conditions for storage and treatment of the tissue before the assay. The activity of cytochrome-c-oxidase was assayed polarographically with a Clark oxygen electrode. Optimal oxygen consumption rates were obtained at a cytochrome-c-concentration above 0.2 mmol/l, in the presence of TMPD, 2.2 mmol/l and ascorbic acid, 4.4 mmol/l as reducing agents. Enzyme proportionality was obtained after correction of the oxygen consumption rates for a blank reaction according to one of three alternatives presented. Variations in the homogenizing technique and the degree of dilution of the homogenate (1:11-1:88) had only moderate effects on the enzyme activity. Optimal storage conditions were evaluated by comparing the enzyme activities measured in fresh muscles, frozen muscles and homogenates prepared from fresh muscles. During all storage conditions significantly higher activities were obtained when sucrose buffer (0.25 mol/l) was used as homogenizing medium as compared to phosphate buffer (0.1 mol/l). Freezing and thawing of the muscle tissue before the assay caused an average decrease in the enzyme activity of 50% (P less than 0.005) as compared to the activity obtained in fresh tissue. This untoward effect of the freezing and thawing was reduced when the enzyme activity was analysed in frozen homogenates prepared from fresh muscles. Thus, an average decrease in the enzyme activity of 15% (P less than 0.05) was found in frozen homogenates prepared in sucrose buffer as compared to the activity obtained in the fresh tissue. These findings emphasize the importance of evaluating the effects of the tissue treatment for comparative studies of maximum enzyme activities in vitro.

Electron Transport Complex IV↗

Energy metabolism in relation to oxygen partial pressure in human skeletal muscle during exercise.

1. The intramuscular oxygen partial pressure (pO2) in human gastrocnemius muscle was monitored during exercise and compared with metabolite concentrations reflecting the energy and the redox state in the tissue. Ten normal subjects and ten patients with peripheral vascular occlusive disease were investigated. 2. In normal subjects the pO2 at the end of exercise was related to the intensity of the exercise, expressed as effect (J/s) per contraction. 3. In both patients and normal subject the pO2 was related to the [ATP]/[ADP] ratio, the [lactate/[pyruvate] ratio and the phosphocreatine concentration in the muscle tissue at rest and during exercise. 4. At each pO2 value, a lower [lactate/[pyruvate] ratio was found in the muscle tissue of the patients compared with that of normal subjects. This was interpreted as a beneficial effect of the higher oxidative-enzyme capacity in the muscle of the patients. 5. The results show the importance of pO2 for the regulation of the energy and the redox state of the tissue. During exercise the changes induced in pO2 and thus the energy state will stimulate the respiratory rate. This might be an important link in triggering the oxidative-enzyme capacity in response to physical training as well as in peripheral vascular occlusive disease.

Energy Metabolism↗