Effect of digoxin on physical performance in healthy man

Summary. The effect of digoxin on the maximal oxygen uptake, the heart rate reaction during submaximal and maximal bicycle exercise and the isokinetic skeletal muscle strength in the thigh was investigated in nine well-trained healthy young men. A daily dose of digoxin of 0·50 mg for 2 weeks, giving a steady state serum digoxin concefltration of 1·0 ± 0·2 nmol/l, did not significantly change maximal oxygen uptake or isokinetic muscle strength. However, the heart rate at rest and during exercise, both at submaximal and maximal levels, decreased significantly during digoxin administration.     

Influence of physical exercise on polyamine synthesis in the rat skeletal muscle

BACKGROUND: Physical exercise and testosterone administration result in a series of adaptive anabolic phenomena in the skeletal muscle. The role of polyamines in these processes has been poorly explored. DESIGN: We measured the activities of polyamine-synthesising enzymes, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) and polyamine content in skeletal muscle of male rats exposed to endurance or resistance exercise, or a single testosterone treatment. Soleus muscle (consisting mainly of slow-twitching oxidative fibres-STO) and extensor digitorum longus (mainly fast-twitching glycolytic muscle fibres-FTG) were analysed for polyamine content by HPLC, and ODC and SAMDC activity. RESULTS: Both endurance and resistance exercise induced a threefold increase in endogenous testosterone production. Two hours after exercise, ODC was increased in STO fibres, returning to baseline after 24 h; in FTG fibres the increase was less prominent. An increase in SAMDC activity occurred in a more sustained manner, with its peak 8 h after exercise. Polyamines were subsequently accumulated in both skeletal muscle fibres, with a rise in putrescine concentration after 2 h, and a fall corresponding to conversion of putrescine to spermidine and spermine by SAMDC. Single dose of 17alpha-methyltestosterone resulted in a similar increase in polyamine-synthesising enzyme activities and polyamine concentrations in the skeletal muscle. CONCLUSION: Polyamine accumulation in the skeletal muscle after physical exercise is likely to occur secondary to testosterone production. Polyamines are apparently involved in the oxidative, but not in glycolytic processes related to muscle adaptation to exercise.     

Effect of physical activity on the day-to-day variation in serum digoxin concentration

Summary. Physical exercise has been found to increase digoxin binding in working skeletal muscle along with a concomitant decrease in serum digoxin concentration. In a recent study on healthy volunteers, moderate physical activity during maintenance digoxin treatment was shown to decrease the renal excretion of digoxin secondary to this redistribution of the drug, thereby affecting the body content of digoxin. In the present study the influence of changes in everyday physical activities, carried out during a 10-h period after ingestion of the daily maintenance digoxin dose, on the steady-state serum digoxin concentration (24 h after the last dose) was studied in 10 digoxin-treated outpatients (61–81 years of age). Compared to normal daily activity, complete bed rest for 10 h after ingestion of the maintenance dose did not affect the steady-state serum digoxin concentration. The lack of such an influence may be explained either by a low degree of everyday physical activity in the investigated patients or to a compensatory increase in the renal excretion of digoxin during the night preceding the serum digoxin measurement. Thus, standardization of physical activity 1–2 h before blood sampling is adequate when analysing the serum digoxin concentration in elderly outpatients.     

运动对大鼠骨骼肌废用性萎缩的恢复及血清雄激素水平的影响

目的探讨在肌肉萎缩和恢复中血清睾酮(ST)水平的变化及不同的锻炼方式对肌萎缩恢复的作用.方法将30只雄性SD大鼠随机分为5组①正常对照组;②外固定3周后即刻宰杀组;③外固定3周后自然恢复3周组;④外固定3周后跑台训练3周组;⑤外固定3周后游泳训练3周组.以放免法测定ST水平.结果固定3周后,即刻宰杀组大鼠ST水平为(0.58±0.24)nmol/L,较正常对照组(6.21±3.51)nmol/L显著下降,两组比较差别有非常显著性意义(P＜0.01);自然恢复组(1.93±0.77)nmol/L和运动组[跑台组(3.01±1.82)nmol/L,游泳组(3.71±2.84)nmol/L]的ST水平均显著高于固定即杀组(0.58±0.24)nmol/L,差别有显著或非常显著性意义(P＜0.05或P＜0.01),但自然恢复组和跑台组仍显著低于对照组水平,差别有显著或非常显著性意义(P＜0.05或P＜0.01),而游泳组已恢复到对照组水平,两组比较差别无显著性意义(P＞0.05);两个运动组之间比较差别无显著性意义(P＞0.05).结论外固定可造成骨骼肌废用性萎缩;解除固定后,萎缩的肌肉可以逐渐恢复,而运动对萎缩肌肉的恢复过程有促进作用,这可能与运动提高机体ST水平有关;游泳锻炼较跑台运动能更有效地提高ST水平.     

Beta-blockade and binding of digoxin to skeletal muscle

Summary. The effect of beta-blockade and a 1-h bicycle exercise test on the digoxin concentration in skeletal muscle (thigh) and serum was studied in 10 healthy men, who had ingested 0·5 mg digoxin daily for 2 weeks. Each subject performed two exercise tests at 100–140 W during maintenance digoxin treatment and 24 h after the latest dose. They rested in the supine position for 2·5 h before the exercise. Sixty minutes before the start of the exercise 0·25 mg/kg b.w. propranolol or saline (control) were injected (single-blind). At the end of the exercise the mean heart rate was 30% lower with beta-blockade (P < 0·001). During exercise the mean skeletal muscle digoxin concentration increased by 29% (P<0·01) in the control situation and by 12% (NS) with beta-blockade. The results indicate that propranolol partly inhibits the exercise-induced increase in skeletal muscle digoxin binding. This might be due to inhibition of a catecholamine-induced stimulation of Na⁺-K⁺ATPase during exercise.     

Effect of resistance exercise on insulin sensitivity of skeletal muscle

Insulin resistance (IR) is the common pathophysiological basis of many metabolic diseases. IR is characterized by decreased glucose uptake in skeletal muscle and adipose tissue, especially in skeletal muscle. Skeletal muscle is the main target tissue of glucose uptake under insulin stimulation. Glucose uptake by skeletal muscle is complex, and it is controlled by many pathways. The PI3K/AKt/GSK-1 signaling pathway is not only the main pathway for insulin signal transduction but also an important mechanism for regulating blood glucose. From the binding of insulin to its receptors on the surface of target cells to the transportation of glucose from extracellular fluid to skeletal muscle, a series of signal transduction processes is completed, any of which potentially affects the physiological effects of insulin and leads to IR. Resistance exercise (RT) can reduce skeletal muscle IR and effectively improve blood glucose control and glycosylated hemoglobin level in patients with type 2 diabetes mellitus (T2DM). However, the exact mechanism by which RT improves skeletal muscle IR remains unclear. Therefore, this paper discusses the above problems by tracking the progress of the literature to deepen the correlation between RT and skeletal muscle insulin sensitivity and provide further evidence for the application of exercise therapy in IR. In conclusion, RT mainly improves insulin sensitivity of skeletal muscle by increasing muscle mass, microvascular blood flow, and glucose transporter-4 expression in skeletal muscle, as well as by reducing lipid accumulation and inflammation in skeletal muscle. Thus, it is potentially useful in the prevention and treatment of T2DM.     

有氧运动对人全基因组表达的影响

目的:观察有氧运动对骨骼肌全基因组表达的影响.方法:选择6名某部队干休所中很少运动、年龄(66±9)岁的健康老年人集进行为期12周太极拳训练.运动前和运动12周后,所有受试都进行了体质评估.测试指标包括身高、体质量、肺活量、台阶指数、最大摄氧量.在训练前后分别对实验对象进行肌活验,提取总RNA,经处理后与Affymetdx U133A基因芯片进行杂交,分析数据.结果:有氧运动可明显改善老年人心肺功能,同时有一定降低体脂(减肥)功效.有氧运动使老年人骨骼肌全基因组表达发生明显改变,筛选出725条表达有差异的基因.本文对表达差异最显著的20条差异表达基因进行研究(3条基因表达上调,17条基因表达下调).根据基因功能分类对比,差异表达基因分别归属8种细胞组分和生物过程,经KEGG搜索找到4条基因的代谢途径.结论:有氧运动可使三羧酸循环相关酶基因表达上调,肌肉蛋白合成相关基因和神经鞘脂类相关基因表达下调,提示有氧运动有助于保护神经细胞的完整性,对抗衰老有积极作用,同时可加速体内脂类物质有氧代谢.     

运动对骨骼肌脂肪代谢与胰岛素敏感性的影响

随着分子生物学的发展,对胰岛素抵抗机制的认识也在逐渐深入,同时也促进了运动影响胰岛素抵抗的机制研究,文章主要就脂肪酸分解对于胰岛素敏感性的调节作用,运动对于肥胖个体胰岛素敏感性作用,以及运动诱导的肌肉细胞内脂肪酸分解的改变对于胰岛素敏感性的作用等进行探讨,以其为糖尿病和胰岛素抵抗患者的运动处方干预提供理论依据和参考。     

Effect of clarithromycin on steady-state digoxin concentrations

OBJECTIVE: To evaluate the magnitude and dose-relatedness of the effect of clarithromycin on the pharmacokinetics of digoxin, and to compare the effects of clarithromycin with those of P-glycoprotein inhibitors. METHODS: Eight Japanese inpatients with congestive heart failure participated in this study. Each patient received oral digoxin therapy for at least 7 days and were coadministered oral clarithromycin to prevent or treat pneumonia. To evaluate the effects of clarithromycin on the pharmacokinetics of digoxin, digoxin concentrations were compared before and after coadministration of clarithromycin. RESULTS: Digoxin concentrations were higher after coadministration of clarithromycin in all patients (before, 0.838 +/- 0.329 ng/mL; after, 1.36 +/- 0.619 ng/mL); (p < 0.005). A significant correlation was observed between the dose of clarithromycin and the percentage of increase in the digoxin concentration. CONCLUSIONS: Digoxin concentrations increased during concomitant administration of clarithromycin, and this effect was dose-dependent on clarithromycin. The percentage increase in digoxin concentrations after the usual oral dose of clarithromycin (400 mg/d) is approximately 70%. Therefore, digoxin concentrations must be monitored carefully after coadministration of clarithromycin, and the doses of digoxin may need readjustment in patients who are concomitantly receiving clarithromycin.     

Glucose uptake and binding of digoxin to skeletal muscle

Summary. Physical exercise induces increased uptake of both digoxin and glucose in exercising skeletal muscle. Glucose uptake could be a regulatory factor for the digoxin binding to skeletal muscle, since in dogs, insulin and glucose infusion have been reported to increase the uptake of digoxin in muscle. In the present study on eight healthy digitalized subjects (0·5 mg digoxin daily) the uptake of glucose in skeletal muscle was achieved by infusion of 6 mg/kg body weight/min glucose, 0·004 IE/kg body weight/min insulin and 300 μg/h somatostatin. Serum and skeletal muscle digoxin levels were analysed before and during the infusion. We found no changes in the digoxin levels in serum and skeletal muscle in spite of an increased uptake of glucose in the muscle. Thus, glucose uptake in skeletal muscle is probably not an important regulatory factor for the change in muscle digoxin binding induced by exercise.     

Effect of nifedipine on serum digoxin concentration and renal digoxin clearance

Nifedipine has been reported either to decrease or not to affect digoxin elimination. We studied the effect of oral nifedipine on steady-state digoxin concentrations and renal clearance in 20 healthy male subjects. After 2 wk of digitalization, all received digoxin, 0.375 mg a day, with placebo for 2 wk, then digoxin and nifedipine, 18.5 +/- 4 mg every 8 hr, for 2 wk, and then digoxin with placebo for 2 wk. Mean (+/- SD) digoxin concentrations of 0.74 +/- 0.20 and 0.75 +/- 0.25 ng/ml on placebo were not altered by nifedipine (0.77 +/- 0.23 ng/ml). Digoxin clearance was 2.2 +/- 0.6 and 2.7 +/- 0.8 ml/kg/min on placebo and 2.5 +/- 0.6 ml/kg/min on nifedipine. No change in pharmacologic effect of digoxin by nifedipine was observed, but mean blood pressure was lower and heart rates were accelerated. These data indicate that oral nifedipine does not alter digoxin concentrations or decrease renal clearance in healthy subjects.     

下坡运动对大鼠骨骼肌肌浆网功能的影响

目的：观测研究下坡(离心)运动对大鼠骨骼肌肌浆网Ca2+-ATP酶活性,Ca2+摄取与释放在量与时程上的影响。此外,测定离子载体的刺激作用,即测定在含与不含(Ca2+离子载体)A23187时Ca2+-ATP酶活性的比值,用以评定囊泡的完整性。方法：成年雄性SD大鼠随机分为对照与离心运动组, 离心运动的大鼠分别于运动后即刻, 4, 24, 48, 72 和144h后取样 (n=7). 离心运动方式采用90min持续跑台下坡运动(-16°;15m/min)。取大鼠红股肌制备组织匀浆, 测定肌浆网Ca2+-ATP酶活性,Ca2+摄取与释放。结果：与对照组[19.25±1.38 nmol ·min-1·(mg protein)-1]相比, 肌浆网Ca2+摄取分别于运动后即刻和4h下降了29% and 36% (P<0.05), 24h依然降低(P<0.05). 肌浆网Ca2+释放与对照组[31.06±2.36 nmol·min-1·(mg protein)-1] 相比,也分别于运动后即刻和4h下降了37% and 39% (P<0.05), 24h持续降低(P<0.05). 用含离子载体测定的肌浆网Ca2+-ATP酶活性运动后4h降低了31%(P<0.05), 并于运动后24h仍然降低 (P<0.05)。运动后, 含与不含A23187时测定的Ca2+-ATP酶活性的比值未见显著性改变, 表明该运动没有明显改变肌浆网膜的完整性。结论：一次性低强度，长时间下坡运动导致肌浆网功能长时间降低, 运动后恢复期两天尚未完全恢复, 亦可构成离心运动诱导的骨骼肌某些功能降低的基础。提示这些变化可能产生于离心收缩时肌节长度不匀一性所造成的张力应激。     

肌肉运动与骨骼肌细胞的凋亡

背景:不少医学研究表明,细胞凋亡能导致大量自由基增多、Ca~(2+)浓度升高、线粒体膜电位下降引起运动能力的下降.因此,研究细胞凋亡与运动训练的关系意义重要.目的:总结与探索关于肌肉运动与骨骼肌细胞凋亡的相关问题.方法:计算机检索中国期刊全文数据(网址http://dlib.cnki.net/kns50/index.aspx)及PubMed数据库(网址http://www.ncbi.nlm.nih.gov/pubmed/)1990-01/2009-06期间的相关文章,检索词为"肌肉运动,骨骼肌细胞凋亡,muscle exercise,apoptosis in the skeletal muscle".纳入与肌肉运动与骨骼肌细胞的凋亡研究现状与发展密切相关.①有关骨骼肌细胞凋亡的研究.②运动与骨骼肌细胞凋亡研究.③运动诱发骨骼肌细胞凋亡的基因调控研究.④骨骼肌细胞凋亡的分子机制研究.⑤同一领域选择近期发表或在权威杂志上发表的文章.排除重复性研究.结果与结论:运动后,正常肌肉中或是病理状态下的肌肉中骨骼肌细胞都会出现凋亡,凋亡的形态学表现与普通凋亡细胞相似,即核固缩、质膜发泡、细胞器紧缩,凋亡小体形成,其凋亡过程大致可分为3个阶段,即启始阶段、效应阶段和降解阶段.骨骼肌细胞凋亡的增加是导致运动性疲劳的重要原因.目前国内外对骨骼肌细胞凋亡的基因调控研究主要是从凋亡调控因子Bcl-2蛋白、肿瘤坏死因子α及死亡蛋白酶半胱氨酸天冬氨酸酶着手.bcl-2基因蛋白的抗凋亡作用主要是通过阻止线粒体通透性转换孔的开放,阻止线粒体释放促凋亡蛋白、防止线粒体膜脂质过氧化以及线粒体基质Ca2+释放实现的.肿瘤坏死因子家族在启动死亡因子及其受体途径中起重要作用,此途径的启动依赖于死亡配体与死亡受体相结合,激活半胱氨酸天冬氨酸酶,导致细胞凋亡.通过研究探索运动强度与骨骼肌细胞凋亡及坏死的界限关系,有利于在运动中认识运动性疲劳产生的机制及有效消除疲劳.     

Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man.

Although insulin stimulates protein synthesis and inhibits protein breakdown in skeletal muscle in vitro, the actual contribution of these actions to its anabolic effects in man remains unknown. Using the forearm perfusion method together with systemic infusion of L-[ring-2,6-3H]phenylalanine and L-[1-14C]leucine, we measured steady state amino acid exchange kinetics across muscle in seven normal males before and in response to a 2-h intraarterial infusion of insulin. Postabsorptively, the muscle disposal (Rd) of phenylalanine (43 +/- 5 nmol/min per 100 ml forearm) and leucine (113 +/- 13) was exceeded by the concomitant muscle production (Ra) of these amino acids (57 +/- 5 and 126 +/- 9 nmol/min per dl, respectively), resulting in their net release from the forearm (-14 +/- 4 and -13 +/- 5 nmol/min per dl, respectively). In response to forearm hyperinsulinemia (124 +/- 11 microU/ml), the net balance of phenylalanine and leucine became positive (9 +/- 3 and 61 +/- 8 nmol/min per dl, respectively (P less than 0.005 vs. basal). Despite the marked increase in net balance, the tissue Rd for both phenylalanine (42 +/- 2) and leucine (124 +/- 9) was unchanged from baseline, while Ra was markedly suppressed (to 33 +/- 5 and 63 +/- 9 nmol/min per dl, respectively, P less than 0.01). Since phenylalanine is not metabolized in muscle (i.e., its only fates are incorporation into or release from protein) these results strongly suggest that in normal man, physiologic elevations in insulin promote net muscle protein anabolism primarily by inhibiting protein breakdown, rather than by stimulating protein synthesis.     

Binding of digoxin to slow- and fast-twitch skeletal muscle fibres

Summary. We have found previously great interindividual variations in the binding of digoxin to skeletal muscle even after standardized rest. The present study was performed in order to find out if there is a difference in the binding of digoxin to slow-and fast-twitch fibres in man at rest and after moderate exercise. Seven healthy digitalized subjects (digoxin 0·50 mg/day) were investigated after 90 min of supine rest and after a 1 h moderate bicycle exercise. Muscle biopsy specimens were taken immediately before and 5 min after exercise and dissected under a microscope to single fibres. After histochemical typing of all fibres the digoxin content in slow-and fast-twitch fibres was measured separately. At rest, digoxin binding to slow-twitch fibres was 33% higher than to fast-twitch fibres (P<0·01). During exercise the digoxin binding increased by 28% in slow-twitch fibres but was unchanged in fast-twitch fibres. The difference in digoxin binding to the two fibre types may explain, at least partly, the interindividual variations in the binding of digoxin to skeletal muscle.     

Determination of free digoxin concentrations in serum for monitoring Fab treatment of digoxin overdose

A rapid method for assessing the free digoxin concentration in the serum of digoxin-overdosed patients receiving treatment with digoxin-specific Fab fragments has been developed. For this method, a protein-free ultrafiltrate is prepared from the patient's serum, and the digoxin in the ultrafiltrate (free digoxin) is measured by fluorescence polarization immunoassay. Both the inaccuracies associated with measurements of total digoxin by immunoassay in the presence of Fab and the long turnaround time associated with measurements of free digoxin by equilibrium dialysis were avoided. Good correlation was observed between measurements of free digoxin by this ultrafiltration technique and by equilibrium dialysis. The ultrafiltration method was used to evaluate the concentrations of free digoxin in a digoxin-overdosed patient treated with Fab at our hospital. In retrospect, the results suggest that her hospital stay could have been shortened by a timely appreciation of her increased concentration of free digoxin. Using the ultrafiltration method, one can determine free digoxin concentrations quickly, conveniently, and accurately in the clinical laboratory. This procedure therefore should be a valuable aid in monitoring the efficacy and adequacy of Fab treatment.     

Digoxin pharmacokinetics in patients with high serum digoxin concentrations

Digitalis intoxication is a frequent iatrogenic effect in patients on treatment with digoxin. In the present study we evaluated the pharmacokinetic behaviour of digoxin and the factors responsible for intoxication by this drug in monitored patients exhibiting clinical signs of overdosing with serum levels > 2 ng/ml. A control group of patients was used as a reference whose population pharmacokinetic parameters obtained by a maximum likelihood method were: V_d= 542–92 ± 274–53 (litre); Cl = 8–73 ± l–55 (litre/h) (mean ± SD). Statistically significant differences (P < 0–001) were found between the mean Cl values in both groups of patients. The difference between the dose–level ratios established in both populations studied also proved to be significant (P < 0–001). Calculation of the optimum dose for each patient showed that the doses recommended in intoxicated patients should be three times lower than those used in the control population. A good correlation was found between the concentrations observed 24 h after administration and the mean concentrations observed at steady state predicted for both population groups. Multiple regression analysis showed that the variables with the greatest predictive value for clearance in intoxicated patients were age and renal function. The modifications observed in the pharmacokinetic behaviour and in the response to digoxin in this type of patient suggest systematic monitoring using pharmacokinetic and clinical criteria jointly.     

Serial serum digoxin concentrations and quantitative electrocardiographic changes.

Four elderly female patients in sinus rhythm and with mild congestive cardiac failure were treated with digoxin and studied over a 6-month period. There were significant linear correlations between serum digoxin concentrations and several quantitative electrocardiographic (ECG) parameters. T-wave amplitude was the most important ECG variable. ECG changes reverted to baseline values when digoxin was discontinued. These findings suggest that quantitative ECG changes are potentially useful in clinical and research situations involving digitalis glycosides.     

抗阻运动对骨骼肌肥厚的影响

背景:抗阻运动能促进骨骼肌生长,导致骨骼肌肥厚。目的:对目前采用细胞生物学及分子生物学方法观察抗阻运动对骨骼肌影响的文献进行综述。方法:检索PubMed数据库中1999/2011-05收录的与抗阻运动后骨骼肌肥厚相关的文章,经筛选共纳入45篇文献,通过PubMed获得文献摘要及部分文献原文,如果没有全文通过Springer或Sciencedirect数据库或其他原文传递方式获得全文,分析抗阻运动对骨骼肌肥厚的研究进展。结果与结论:抗阻运动后循环同化激素包括生长激素、胰岛素样生长因子1和睾酮发生应答性变化,对骨骼肌肥厚产生影响。抗阻运动对骨骼肌细胞生物学影响的研究主要集中在雷帕霉素靶蛋白介导骨骼肌蛋白合成途径,前列腺素、肿瘤坏死因子α介导的炎性机制与增肌关系和张力感受器在信号改变后对增肌的影响3个方面。     

Influence of everyday physical activity on the serum digoxin concentration in digoxin-treated patients

Summary. Thirteen patients admitted to hospital because of known or suspected cardiac disease who had been treated with digoxin within, at least, the previous month were investigated. Blood samples for serum digoxin analysis by radioimmunoassay were taken before and after 40 min rest in supine in the ward and later in the outpatient clinic, all samples taken about 24 h after the last dose of digoxin. The serum digoxin concentration measured before rest in the outpatient clinic was significantly lower than those measured in the ward before and after rest. This is possibly related to physical activity prior to blood sampling since after 40 min rest in the outpatient clinic the serum digoxin concentration had increased and the concentration after rest was not significantly different from the concentrations measured in the ward. In analogy with a previous finding of a decrease in serum digoxin concentration during exercise in healthy subjects ingesting digoxin, the present results suggest that everyday physical activity affects the serum digoxin concentration. This must be taken into account when interpreting the results of serum digoxin measurements.