Skeletal muscle changes after endurance training at high altitude.

The effects of endurance training on the skeletal muscle of rats have been studied at sea level and simulated high altitude (4,000 m). Male Wistar rats were randomly assigned to one of four groups: exercise at sea level, exercise at simulated high altitude, sedentary at sea level, and sedentary at high altitude (n = 8 in each group). Training consisted of swimming for 1 h/day in water at 36 degrees C for 14 wk. Training and exposure to a high-altitude environment produced a decrease in body weight (P less than 0.001). There was a significant linear correlation between muscle mass and body weight in the animals of all groups (r = 0.89, P less than 0.001). High-altitude training enhanced the percentage of type IIa fibers in the extensor digitorum longus muscle (EDL, P less than 0.05) and deep portions of the plantaris muscle (dPLA, P less than 0.01). High-altitude training also increased the percentage of type IIab fibers in fast-twitch muscles. These muscles showed marked metabolic adaptations: training increased the activity levels of enzymes involved in the citric acid cycle (citrate synthase, CS) and the beta-oxidation of fatty acids (3 hydroxyacyl CoA dehydrogenase, HAD). This increase occurred mainly at high altitude (36 and 31% for HAD in EDL and PLA muscles; 24 and 31% for CS in EDL and PLA muscles). Training increased the activity of enzymes involved in glucose phosphorylation (hexokinase). High-altitude training decreased lactate dehydrogenase activity. Endurance training performed at high altitude and sea level increased the isozyme 1-to-total lactate dehydrogenase activity ratio to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)     

High altitude tissue adaptation in Andean coots: capillarity,fibre area,fibre type and enzymatic activities of skeletal muscle

Capillarity, fibre types, fibre area and enzyme activities of different skeletal muscles (pectoralis, extensor digitorum longus), tibialis anterior, plantaris and the myocardium were compared in Andean coot (Fulica americana peruviana) native to high altitude (Junín, Perú, 4200 m) and the same species nesting at sea level. Numbers of capillaries per square millimeter were higher in all high-altitude muscles when compared with sea-level muscles (P<0.0001). Moreover, values for capillaries per fibre and capillaries in contact with each fibre were higher in digitorum and tibialis high-altitude muscles. Muscle fibres were classified as Type I, Type IIA or Type IIB on the basis of their myofibrillar ATPase pH lability. Pectoralis muscle of high-altitude and sea-level coots presented only fibres of Type IIA. In contrast, all the leg muscles studied showed a mosaic pattern of the three fibre types. Fibre areas were determined using a Leitz Texture Analysis System. Significant differences in fibre area were observed (P<0.01) between high-altitude and sea-level muscles. Mean muscle fibre diameters were also lower in the high-altitude group than in the sea-level group. The enzyme activities studied were hexokinase, lactate dehydrogenase, citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase. The oxidative capacity, as reflected by citrate synthetase and hydroxyacyl-CoA-dehydrogenase activities, was greater for myocardial and pectoralis than for leg muscles. However, analysis of maximal enzyme activities showed that there were no significant differences between the glycolytic and oxidative enzyme activities of high-altitude and sea-level coots. These results suggest that in Andean coots genetically adapted to high altitude, changes in muscle capillarity and fibre size, in addition to high haemoglobin O₂ affinity and low haemoglobin concentration, are sufficient to allow adequate energy production without increases in enzymatic activities.Abbreviations BSA bovine serum albumin - C:F ratio Capillaries per fibre - CAF Capillaries in contact with each fibre - CD capillary density (mm^-2) - CS citrate synthetase - EDL muscularis digitorum longus - fra fraction reduction area - HA high altitude - HAD hydroxyacyl-CoA-dehydrogenase - HK hexokinase - LDH lactate dehydrogenase - P ₅₀ PO₂ at which hemoglobin is half saturated with O₂ - P _aO₂ arterial partial pressure of oxygen - PAS periodic acid-schiff - PEC muscularis pectoralis - PLA muscularis planaris - P _tO₂ mean tissue oxygen pressure - P _vO₂ mixed venous partial pressure of oxygen - SD standard deviation - SL sea level - TA muscularis tibialis anterior - TAS texture analysis system     

Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine. The European Study Group

ObjectiveTo assess intermittent treatment over 12 months in patients with symptomatic gastro-oesophageal reflux disease.DesignRandomised, multicentre, double blind, controlled study. Patients with heartburn and normal endoscopy results or mild erosive changes received omeprazole 10 mg or 20 mg daily or ranitidine 150 mg twice daily for 2 weeks. Patients remaining symptomatic had omeprazole 10 mg or ranitidine dose doubled for another 2 weeks while omeprazole 20 mg was continued for 2 weeks. Patients who were symptomatic or mildly symptomatic were followed up for 12 months. Recurrences of moderate or severe heartburn during follow up were treated with the dose which was successful for initial symptom control.SettingHospitals and primary care practices between 1994 and 1996.Subjects677 patients with gastro-oesophageal reflux disease.Results704 patients were randomised, 677 were eligible for analyses; 318 reached the end of the study with intermittent treatment without recourse to maintenance antisecretory drugs. The median number of days off active treatment during follow up was 142 for the entire study (281 for the 526 patients who reached a treatment related end point). Thus, about half the patients did not require treatment for at least 6 months, and this was similar in all three treatment groups. According to outcome, 378 (72%) patients were in the best outcome ranks (no relapse or one (or more) relapse but in remission until 12 months); 630 (93%) had three or fewer relapses in the intermittent treatment phase. Omeprazole 20 mg provided faster relief of heartburn. The results were similar in patients with erosive and non-erosive disease.ConclusionsIntermittent treatment is effective in managing symptoms of heartburn in half of patients with uncomplicated gastro-oesophageal reflux disease. It is simple and applicable in general practice, where most patients are seen.

Key messages

• Symptomatic gastro-oesophageal disease can be managed successfully in half of patients with intermittent treatment with antisecretory drugs
• Omeprazole 20 mg once daily gives more rapid relief of symptoms than either omeprazole 10 mg once daily or ranitidine 150 mg twice daily. However, the choice of antisecretory drug has little effect on the overall outcome
• Relapses are relatively infrequent and can be managed with short courses of repeat treatment
• Starting intermittent treatment with omeprazole 20 mg once daily is more cost effective than a dose titration approach with omeprazole 10 mg once daily or ranitidine 150 mg twice daily
• An intermittent treatment strategy is simple and applicable in general practice, where most of these patients are seen

     

Effects of hindlimb suspension and androgen treatment on testosterone receptors in rat skeletal muscles

This study tested the specific and combined effects of testosterone treatment and hindlimb suspension (HS) on the properties of steroid receptors in skeletal muscle. Male rats were either administered weekly high doses of testosterone heptylate (10 mg x kg(-1)) or olive oil placebo, and were either tail-suspended or acted as controls. After 3 weeks of treatment, three muscles were excised from each animal, soleus (SOL), extensor digitorum longus (EDL), and plantaris. The results showed that the testosterone treatment was unable to minimise the HS-induced atrophy of skeletal muscle. As expected, HS altered the fibre-type composition of SOL muscles (-33% of type I, +188% and +161% of type IIa and intermediate fibres respectively, P < 0.01). No overall effect of treatment was detected on the fibre-type composition of either slow or fast-twitch muscles. Binding capacity determined by a radiocompetition technique was increased by HS, especially in SOL and EDL muscles (P < 0.01), while HS or steroid treatment decreased the affinity of the steroid receptors. The combination of HS and testosterone administration resulted in a decrease in binding capacity and affinity of steroid receptors in skeletal muscles. Steroid receptors in fast-twitch muscles exhibited a higher affinity than those in slow-twitch muscles, and it is suggested that it is likely that testosterone treatment is more effective in fast-twitch than in slow-twitch muscles. It was concluded that the lack of preventive effect of testosterone treatment on HS-induced SOL muscle atrophy could be explained by both a decrease in steroid sensitivity and the removal of mechanical factors.     

Quantitative assessment of degenerative changes in soleus muscle after hindlimb suspension and recovery

The aim of this study was to quantify the degenerative and regenerative changes in rat soleus muscle resulting from 3-week hindlimb suspension at 45° tilt (HS group, n = 8) and 4-week normal cage recovery (HS-R group, n = 7). Degenerative changes were quantified by microscope examination of muscle cross sections, and the myosin heavy chain (MHC) composition of soleus muscles was studied by sodium dodecyl sulphate polyacrylamide gel electrophoresis. At the end of 3-week hindlimb suspension, histological signs of muscle degenerative changes were detected in soleus muscles. There was a significant variability in the percentage of fibres referred to as degenerating (%dg) in individual animals in the HS group [%dg = 8.41 (SEM 0.5)%, range 4.66%–14.08%]. Moreover, %dg varied significantly along the length of the soleus muscle. The percentage of fibres with internal nuclei was less than %dg in HS-soleus muscles [4.12 (SEM 0.3)%, range 1.24%–8.86%]. In 4-week recovery rats, the greater part of the fibres that were not referred to as normal, retained central nuclei [15.8 (SEM 2.2)%, range 6.2%–21.1%]. A significant increase in the slow isoform of MHC was recorded in the HS-R rats, compared to muscles from age-matched rats (P < 0.01). These results would suggest that a cycle of myofibre degeneration-regeneration occurred during HS and passive recovery, and that the increased accumulation of slow MHC observed in soleus muscles after recovery from HS could be related to the prevalence of newly formed fibres. Accepted: 14 October 1996     

Endurance training affects myosin heavy chain phenotype in regenerating fast-twitch muscle

Bigard, Xavier A., Chantal Janmot, Danièle Merino,Françoise Lienhard, Yannick C. Guezennec, and Anne D'Albis.Endurance training affects myosin heavy chain phenotype inregenerating fast-twitch muscle. J. Appl.Physiol. 81(6): 2658-2665, 1996.The aim of thisstudy was to analyze the effects of treadmill training (2 h/day, 5 days/wk, 30 m/min, 7% grade for 5 wk) on the expression of myosinheavy chain (MHC) isoforms during and after regeneration of afast-twitch white muscle [extensor digitorum longus (EDL)]. Male Wistar rats were randomly assigned to a sedentary(n = 10) or an endurance-trained (ET;n = 10) group. EDL muscle degeneration and regeneration were induced by two subcutaneous injections of a snaketoxin. Five days after induction of muscle injury, animals were trainedover a 5-wk period. It was verified that ~40 days after venomtreatment, central nuclei were present in the treated EDL muscles fromsedentary and ET rats. The changes in the expression of MHCs in EDLmuscles were detected by using a combination of biochemical andimmunocytochemical approaches. Compared with contralateral nondegenerated muscles, relative concentrations of types I, IIa, andIIx MHC isoforms in ET rats were greater in regenerated EDL muscles(146%, P < 0.05; 76%,P < 0.01; 87%,P < 0.01, respectively). Their elevation corresponded to a decreasein the relative concentration of type IIb MHC (36%,P < 0.01). Although type I accountedfor only 3.2% of total myosin in regenerated muscles from the ETgroup, the cytochemical analysis showed that the proportion of positive staining with the slow MHC antibody was markedly greater in regenerated muscles than in contralateral ones. Collectively, these results demonstrate that the regenerated EDL muscle is sensitive to endurance training and suggest that the training-induced shift in MHC isoforms observed in these muscles resulted from an additive effect of regeneration and repeated exercise.

     

Leptin receptor-deficient obese Zucker rats reduce their food intake in response to hypobaric hypoxia

Exposure to hypoxia induces anorexia in humans and rodents, but the role of leptin remains under discussion and that of orexigenic and anorexigenic hypothalamic neuropeptides remains unknown. The present study was designed to address this issue by using obese (Lepr(fa)/Lepr(fa)) Zucker rats, a rat model of genetic leptin receptor deficiency. Homozygous lean (Lepr(FA)/Lepr(FA)) and obese (Lepr(fa)/Lepr(fa)) rats were randomly assigned to two groups, either kept at ambient pressure or exposed to hypobaric hypoxia for 1, 2, or 4 days (barometric pressure, 505 hPa). Food intake and body weight were recorded throughout the experiment. The expression of leptin and vascular endothelial growth factor (VEGF) genes was studied in adipose tissue with real-time quantitative PCR and that of selected orexigenic and anorexigenic neuropeptides was measured in the hypothalamus. Lean and obese rats exhibited a similar hypophagia (38 and 67% of initial values at day 1, respectively, P < 0.01) and initial decrease in body weight during hypoxia exposure. Hypoxia led to increased plasma leptin levels only in obese rats. This resulted from increased leptin gene expression in adipose tissue in response to hypoxia, in association with enhanced VEGF gene expression. Increased hypothalamic neuropeptide Y levels in lean rats 2 days after hypoxia exposure contributed to accounting for the enhanced food consumption. No significant changes occurred in the expression of other hypothalamic neuropeptides involved in the control of food intake. This study demonstrates unequivocally that altitude-induced anorexia cannot be ascribed to anorectic signals triggered by enhanced leptin production or alterations of hypothalamic neuropeptides involved in anabolic or catabolic pathways.