Experiment K-6-21. Effect of microgravity on 1) metabolic enzymes of type 1 and type 2 muscle fibers and on 2) metabolic enzymes, neutransmitter amino acids, and neurotransmitter associated enzymes in motor and somatosensory cerebral cortex. Part 1: Metabolic enzymes of individual muscle fibers; part 2: metabolic enzymes of hippocampus and spinal cord

The individual fibers of any individual muscle vary greatly in enzyme composition, a fact which is obscured when enzyme levels of a whole muscle are measured. The purpose of this study was therefore to assess the changes due to weightless on the enzyme patterns composed by the individual fibers within the flight muscles. In spite of the limitation in numbers of muscles examined, it is apparent that: (1) that the size of individual fibers (i.e., their dry weight) was reduced about a third, (2) that this loss in dry mass was accompanied by changes in the eight enzymes studied, and (3) that these changes were different for the two muscles, and different for the two enzyme groups. In the soleus muscle the absolute amounts of the three enzymes of oxidative metabolism decreased about in proportion to the dry weight loss, so that their concentration in the atrophic fibers was almost unchanged. In contrast, there was little loss among the four enzymes of glycogenolysis - glycolysis so that their concentrations were substantially increased in the atrophic fibers. In the TA muscle, these seven enzymes were affected in just the opposite direction. There appeared to be no absolute loss among the oxidative enzymes, whereas the glycogenolytic enzymes were reduced by nearly half, so that the concentrations of the first metabolic group were increased within the atrophic fibers and the concentrations of the second group were only marginally decreased. The behavior of hexokinase was exceptional in that it did not decrease in absolute terms in either type of muscle and probably increased as much as 50 percent in soleus. Thus, their was a large increase in concentration of this enzyme in the atrophied fibers of both muscles. Another clear-cut finding was the large increase in the range of activities of the glycolytic enzymes among individual fibers of TA muscles. This was due to the emergence of TA fibers with activities for enzymes of this group extending down to levels as low as those found in control soleus muscles. It would be interesting to know if this represents a transition stage, and whether with prolonged weightlessness most of the fibers would be transformed into a low glycogenolytic type

Cosmos 2044

The effects of microgravity and hind limb suspension on the enzyme patterns are assessed within a slow twitch muscle (soleus) and a fast twitch muscle (tibialis anterior). Studies were made on 95 soleus fibers and about 300 tibialis anterior (TA) fibers. Over 2200 individual enzyme measurements were made. Six key metabolic enzymes (hexokinase, pyruvate kinease, citrate kinase, beta-hydroxyacyl CoA dehydrogenase, glucose-6-P dehydrogenase, and aspartate aminotransferase) plus glutaminase and glutamate decarboxylase, as well as glutamate, aspartate, and GABA, were measured in 11 regions of the hippocampal formation of synchronous, flight, and tail suspension rats. Major differences were observed in the normal distribution of each enzyme and amine acid, but no substantive effects of either microgravity or tail suspension on these patterns were clearly demonstrated

Mechanisms of Impaired Exercise Capacity in Short Duration Experimental Hyperthyroidism

Abstract To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26±1 yr (mean±SE) before and after 2 wk of daily ingestion of 100 pg of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P < 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08±0.17 vs. 2.94±0.19 l/min; P < 0.001) despite increased heart rate and cardiac output at maximal exercise (P < 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P < 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P < 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P < 0.001) and glycolytic (P < 0.05) enzymes in skeletal muscle and a 15% decrease in type 11A muscle fiber cross-sectional area (P < 0.05). Lean body mass was reduced (P < 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P < 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced. (J. Clin

Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Association Between Biochemical And Physiological Properties In Single Motor Units

Motor units from the cat tibialis posterior muscle were examined for an association between physiological and biochemical properties. Functionally isolated motor units were categorized on the basis of their physiological properties. This was followed by quantitative microbiochemical analysis of single muscle fibers from each unit, identified in cross sections using the glycogenâ€depletion method. The activities of malate dehydrogenase and β;â€hydroxyacylâ€CoA dehydrogenase distinguished between fatigable (type FF) and fatigueâ€resistant (types FR and S) units. The activities of both lactate dehydrogenase and adenylokinase were higher in fastâ€than in slowâ€contracting units. Cluster analyses, based on both physiological and biochemical properties alone, produced groupings identical to types FF, FR, and S. The association between physiological and biochemical properties substantiates the idea that biochemically distinct groups of motor units correspond to physiologically identifiable groups. Copyright © 1988 John Wiley & Sons, Inc