Gonadectomy and reduced physical activity: effects on skeletal muscle

OBJECTIVES: To examine the effects of testosterone (TST) loss on skeletal muscle contractile function and the potential interactive effects of TST loss and physical inactivity. DESIGN: Randomized control trial. ANIMALS: Forty-eight male rats (age, 6mo) were placed into control (Con) or gonadectomized (Orx) groups. INTERVENTION: Two weeks after Orx or sham surgery, half the Con and Orx rats were hind-limb unloaded (HLU) to reduce muscle activity for 2 weeks. Subsequently, in situ contractile function tests were performed on the soleus (SOL), plantaris (PLAN), peroneus longus (PER), and extensor digitorum longus (EDL). These 4 muscles and gastrocnemius (GAST) then were removed, weighed, sectioned, and stained with adenosine triphosphatase for fiber typing and fiber area measures. MAIN OUTCOME MEASURES: Peak tetanic tension (P(0)), time to peak twitch contraction (TPT), half relaxation time (RT(1/2)), muscle mass, fiber area, and specific tension (ratio of P(0)/muscle mass). RESULTS: Body weight and muscle mass were similar in the Con and Orx groups. The ratio of P(0) to muscle mass was significantly (p <.05) reduced with Orx in SOL (20%), PLAN (18%), PER (28%), and EDL (20%). TPT and RT(1/2) were significantly faster after Orx in PLAN, PER, and EDL. HLU significantly reduced muscle mass in SOL, PLAN, and GAST in Orx and intact groups. HLU also caused a significant decline in SOL and PLAN P(0). The loss in P(0) in the Orx-HLU rats was no greater than the decline in P(0) with HLU alone. CONCLUSIONS: Gonadectomy results in a loss of P(0) regardless of muscle fiber type or function, it is likely to speed up TPT and RT(1/2), and it does not exacerbate HLU-related atrophy and P(0) loss. Findings may have implications for men with reduced TST levels, as in aging, for instance.     

The effects of non-weight bearing on skeletal muscle in older rats: an interrupted bout versus an uninterrupted bout

Age-related changes in skeletal muscle, in combination with bed rest, may result in a poorer rehabilitation potential for an elderly patient. The purpose of this study was to determine the effects of non-weight bearing (hind limb unweighting [HU]) on the soleus and extensor digitorum longus (EDL) in older rats. Two non-weight bearing conditions were used: an uninterrupted bout of HU and an interrupted bout of HU. Twenty-one rats were randomly placed into 1 of 3 groups: control, interrupted HU (2 phases of 7 days of HU, separated by a 4-day weight-bearing phase) and an uninterrupted HU (18 uninterrupted days of HU). Following non-weight bearing, the soleus and EDL muscles were removed. Fiber type identification was performed by myofibrillar ATPase and cross-sectional area was determined. The findings suggest that any period of non-weight bearing leads to a decrease in muscle wet weight (19%-45%). Both type I and type II fibers of the soleus showed atrophy (decrease in cross-sectional area, 35%-44%) with an uninterrupted bout of non-weight bearing. Only the type II fibers of the soleus showed recovery with an interrupted bout of weight bearing. In the EDL, type II fibers were more affected by an uninterrupted bout of non-weight bearing (15% decrease in fiber size) compared to the type I fibers. EDL type II fibers showed more atrophy with interrupted bouts of non-weight bearing than with a single bout (a 40% compared to a 15% decrease). This study shows that initial weight bearing after an episode of non-weight bearing may be damaging to type II fibers of the EDL.     

Effects of inactivity on glycolytic capacity of single skeletal muscle fibers in adult and aged rats

The purpose of this study was to determine the effects of inactivity on lactate dehydrogenase (LDH) enzyme activity (expressed in nmol/g dry weight x hour) in single skeletal musclefibers from the soleus muscle in adult and aged rats. Fourteen 12-month-old andfifteen 30-month-old Fisher 344 Brown Norway F1 Hybrid rats were randomly assigned to control, 1 week of hindlimb unweighting (HU1), or 2 weeks of hindlimb unweighting (HU2). With age, a significant decrease in LDH enzyme activity occurred in type I skeletal muscle fibers (29.5%, P < 0.05). Following HU2, individual type I skeletal muscle fibers from the 12-month-old animals showed a 33.3% increase in LDH activity. In contrast, individual type I fibers from the aged animals showed a 50.0% increase after HU1. In conclusion, the baseline levels of LDH activity were significantly less in aged versus adult rats. The timing of the skeletal muscle adaptation to inactivity was different between young and old animals, such that the older animals responded to inactivity before the younger animals. These biochemical changes may have an impact on the fatigability of the muscle following inactivity. Thefindings indicate that treatment during bed rest for the older adult may be different than that for the younger adult.     

大鼠脊神经损伤后所支配骨骼肌及其运动终板的退变

目的：研究大鼠脊神经运动根损伤后所支配的骨骼肌组织形态学变化，为临床提供理论基础。方法：选用SPF级成年雄性SD大鼠32只．随机分为2组：一组单纯切断左侧的L4脊神经前根，另一组同时切断左侧的L4和L5脊神经前根；以各大鼠的左侧为实验侧，右侧为自身对照侧，分别于手术后6周和4个月时测定双侧趾长伸肌的肌湿重和肌细胞截面积，并观察骨骼肌运动终板的形态。结果：术后6周：单纯L4神经根切断组和L4，5神经根切断组的实验侧肢体功能较正常对照侧均有明显损伤（P〈0．01）．运动终板崩解变性。术后4个月：单纯L4神经根切断组的实验侧肢体功能接近正常（P〉0．05），再生运动终板结构接近正常；L4，5神经根切断组的实验侧肢体功能与对照侧相比．有极显著性差异（P〈0．01），运动终板完全消失。结论：单纯L4神经根切断近期可造成肢体功能损伤，但随时间推移，损害逐渐减轻，甚至消失；但若合并L5神经根损伤将造成肢体功能的永久性损害。     

Alterations in skeletal muscle related to impaired physical mobility: An empirical model

The objective of this investigation was to study impaired physical mobility and the resulting skeletal muscle atrophy. An animal model was used to study morphological adaptations of the soleus and plantaris muscles to decreased loading induced by hindlimb suspension of an adult rat for 7, 14, and 28 consecutive days. Alterations in weight, skeletal muscle growth, and changes in fiber type composition were studied in synergistic plantar flexors of the rat hindlimb. Body weight and the soleus muscle mass to body mass ratio demonstrated significant progressive atrophy over th 28-day experimental period with the most significant changes occurring in the first 7 days of hindlimb suspension. Hindlimb suspension produced atrophy of Type I and Type lla muscle fibers as demonstrated by significant decreases in fiber cross-sectional area (γm²). These latter changes account for the loss of contractile force production reported in the rat following hindlimb unloading. When compared to traditional models of hindlimb suspension and immobilization, the ISC model produces a less severe atrophy while maintaining animal mobility and health. We conclude that it is the preferred animal model to address nursing questions of impaired physical mobility. © 1993 John Wiley & Sons, Inc.     

Aging alters neuronal nitric oxide release from rat mesenteric arteries: role of presynaptic beta-adrenoceptors

This study examines the influence of aging on the neuronal nitric oxide (NO) and noradrenaline (NA) release elicited by electrical field stimulation (EFS; 200 mA, 0.3 ms, 1-16 Hz, 30 s) in endothelium-denuded mesenteric arteries from young and old rats, as well as the influence of the presynaptic beta-adrenoceptors in that release. EFS induced frequency-dependent contractions. N(G)-nitro-l-arginine methyl ester (l-NAME) only enhanced EFS-elicited contractions in arteries from young rats. Capsaicin did not alter the EFS-induced contractions in either age group. Clenbuterol did not modify the contraction elicited by EFS in arteries from young or old rats either. A subsequent addition of l-NAME also induced an increase in the EFS-induced response in arteries from both age groups. In old rats, the presence of propranolol did not alter the response induced by EFS, and the subsequent addition of clenbuterol or clenbuterol plus l-NAME did not affect this response. In precontracted segments, sodium nitroprusside or clenbuterol induced similar relaxation in both age groups. None of the drugs used altered the response to exogenous NA or basal tone. In arteries preincubated with [(3)H]NA, EFS induced (3)H release, which remained unmodified in the presence of clenbuterol or propranolol in young rats, whereas clenbuterol increased the (3)H overflow in old rats, and this effect was abolished by propranolol. These drugs did not alter the basal (3)H efflux and indicate that in rat mesenteric arteries EFS induces NA release in both age groups, and only NO release in young animals. Activation of presynaptic beta-adrenoceptors increased NA and probably NO release in aged rats.     

Strenuous exercise-induced alterations of muscle fiber cross-sectional area and fiber-type distribution in steroid myopathy rats

OBJECTIVE: To investigate the effect of exercise intensity on the muscle histopathology in steroid myopathy rats. DESIGN: Eight-week-old male Wistar rats (n=40) were divided into four groups: a control group (n=4), steroid-only group (n=12), moderate exercise + steroid group (n=12), and a high-intensity exercise + steroid group (n=12). Five weeks after triamcinolone injection, the soleus muscle (SOL) and extensor digitorum longus muscle (EDL) were removed and stained for adenosine triphosphatase (ATPase). The muscle fiber area and fiber type distribution of each fiber type were measured. RESULTS: In the high-intensity exercise group, the type I fibers in the SOL and the type IIb fibers in the EDL showed significant atrophy. In the fiber distribution of the SOL, type I fibers decreased in the steroid-only group and high-intensity exercise group as compared with the control, whereas there was a significant increase in the moderate exercise group vs. the steroid-only group. In the EDL, type I fibers were significantly greater in the moderate- and high-intensity exercise groups, whereas type IIb fibers significantly decreased in the moderate-exercise group as compared with the steroid-only group. CONCLUSIONS: In rats with steroid myopathy, high-intensity exercise caused changes such as muscle atrophy. The fiber type distribution of the SOL changed from type II fibers to type I fibers in the moderate exercise group. Intensive exercise, however, resulted in transformation from type I to type II in the fiber type distribution. For the EDL, no significant fiber type changes were observed with high-intensity exercise when compared with moderate exercise.     

慢性骨筋膜室综合征动物模型的建立及骨骼肌病理变化的实验研究

目的探讨慢性骨筋膜室综合征所致比目鱼肌(红肌)、伸趾长肌(白肌)的病理变化。方法90只日本白兔分成15组。他们的右小腿被小儿充气式血压计袖带间断性、重复性的压迫。结果在40mmHg压力1d和3d压迫组中,骨骼肌细胞呈现炎性水肿和细胞直径增加。在80和120mmHg压力3d压迫组及40mmHg压力7、14和28d压迫组中,可见少量的坏死和有中性核细胞浸润的骨骼肌细胞,表明了早期细胞坏死。然而,在80和120mmHg压力7、14和28d压迫组中,骨骼肌细胞表明了显著的变性改变。这种改变是在压力较高组以及比目鱼肌比伸趾长肌更显著。结论重复性压迫可引起严重的骨骼肌组织的变性,特别是红肌。     

尾吊影响大鼠比目鱼肌Dystrophin表达分布以及血清乳酸脱氢酶活性

背景:抗肌萎缩蛋白Dystrophin在肌肉运动性损伤时易发生改变。目的:观察模拟失重效应对大鼠比目鱼肌抗肌萎缩蛋白Dystrophin表达、分布及血清乳酸脱氢酶活性的影响。方法:采用大鼠后肢尾吊模拟失重效应模型,分别在尾吊1,4,7,10,14d分离SD大鼠比目鱼肌并提取血清进行检测。结果与结论:随着尾吊时间的延长,大鼠肌纤维横截面积减小;肌膜上Dystrophin呈现弥散性分布的趋势,甚至出现Dystrophin断裂现象;Dystrophin mRNA表达下降。同时尾吊7d,大鼠血清乳酸脱氢酶活性升高。提示失重引起的肌萎缩,伴随着Dystrophin mRNA的表达下降和蛋白分布弥散性变化,而乳酸脱氢酶活性变化提示失重性肌萎缩可能与肌损伤的发生有关。     

Clenbuterol Ingestion Causing Prolonged Tachycardia,Hypokalemia, and Hypophosphatemia with Confirmation by Quantitative Levels

Background: Clenbuterol is a long acting beta₂-adrenergic agonist used in the treatment of pulmonary disorders. Acute clenbuterol toxicity resembles that of other beta₂-adrenergic agonists. Most previously reported cases of clenbuterol toxicity describe patients who ate livestock illicitly treated with clenbuterol. Case Report: We report a case of human clenbuterol toxicity confirmed and correlated with qualitative and quanitative serum clenbuterol assays. This poisoned patient, a 28-year-old woman, developed sustained sinus tachycardia at 140/min, hypokalemia (2.4 mEq/L, 2.4 mmol/L), hypophosphatemia (0.9 mg/dL, 0.29 mmol/L), and hypomagnesemia (1.52 mg/dL, 0.76 mmol/L) after ingesting a reportedly small quantity of clenbuterol. The patient received repeated doses of metoprolol to treat her cardiovascular stimulation and potassium chloride to treat her hypokalemia. She remained symptomatic for more than 20 hours after the ingestion. Analysis by enzyme-linked immunosorbent assay and liquid chromatography/mass spectrometry revealed a serum clenbuterol concentration of 2.93 mcg/L 3 hours after the ingestion and an undetectable serum concentration 20 hours after ingestion. It is noteworthy that at a serum concentration below the limit of detection by liquid chromatography/mass spectrometry, the patient remained symptomatic. Acute clenbuterol toxicity is rarely reported following illicit use in humans, and this is the first such case to provide confirmatory toxicological analysis.     

Resistance exercise training attenuates wasting of the extensor digitorum longus muscle in mice bearing the colon-26 adenocarcinoma

Progressive wasting of skeletal muscle is a significant side effect of malignancy. Perturbations in protein metabolism contribute to this state of wasting. Resistance exercise increases protein synthesis and mass of healthy muscles and counteracts muscle wasting associated with several catabolic conditions. It is not known whether resistance exercise training can counteract cancer-induced muscle wasting. This study examined the effect of resistance exercise training on muscle mass and protein content in 9 mice bearing the colon-26 adenocarcinoma. The dorsiflexor (extensor digitorum longus [EDL] and tibialis anterior) and plantar flexor (soleus, plantaris, and gastrocnemius) muscles of 1 leg of the tumor-bearing and the control mice were stimulated to contract eccentrically and concentrically, respectively, using an electrical stimulation protocol consisting of 10 sets of 6 repetitions per session. The muscles were stimulated on alternate days for a total of 8 sessions. The weight and protein content of the stimulated EDL muscle in the tumor-bearing mice were significantly higher (62% and 25%, respectively) than those of the nonstimulated EDL. Training did not have significant effects on the weight or protein content of the other muscles of the tumor-bearing mice, nor did it have significant effects on the muscles of the controls. These findings demonstrated that resistance training attenuated cancer-induced muscle wasting and protein depletion in the EDL muscle. The lack of an effect of the same training protocol on the EDL muscle in the control mice suggests that the amount and intensity of exercise training that is adequate to attenuate muscle wasting may not be adequate to induce hypertrophy of healthy muscles.     

Effect of early low-intensity exercise on rat hind-limb muscles following acute ischemic stroke

This study examined the effects of daily low-intensity exercise following acute stroke on mass, Type I and II fiber cross-sectional area, and myofibrillar protein content of hind-limb muscles in a rat model. Adult male Sprague-Dawley rats were randomly assigned to 1 of 4 groups (n = 7-9 per group): stroke (occlusion of the right middle cerebral artery [RMCA]), control (sham RMCA procedure), exercise, and stroke-exercise. Beginning 48 hours post-stroke induction/sham operation, rats in the exercise group had 6 sessions of exercise in which they ran on a treadmill at grade 10 for 20 min/day at 10 m/min. At 8 days poststroke, all rats were anesthetized and soleus, plantaris, and gastrocnemius muscles were dissected from both the affected and unaffected sides. After 6 sessions of exercise following acute ischemic stroke, the stroke-exercise group showed the following significant (p < .05) increases compared to the stroke-only group: body weight and dietary intake, muscle weight of affected soleus and both affected and unaffected gastrocnemius muscle, Type I fiber cross-sectional area of affected soleus and both affected and unaffected gastrocnemius muscle, Type II fiber cross-sectional area of the unaffected soleus, both affected and unaffected plantaris and gastrocnemius muscle, Type II fiber distribution of affected gastrocnemius muscle, and myofibrillar protein content of both affected and unaffected soleus muscle. Daily low-intensity exercise following acute stroke attenuates hind-limb muscle atrophy in both affected and unaffected sides. The effects of exercise are more pronounced in the soleus and gastrocnemius as compared to the plantaris muscle.     

Deleterious effects of chronic clenbuterol treatment on endurance and sprint exercise performance in rats

The beta(2)-adrenergic agonist, clenbuterol, has powerful muscle anabolic and lipolytic effects and is used by athletes to improve exercise performance; however, its use in conjunction with different forms of exercise training has received limited attention. Since previous studies have reported that chronic use of other beta(2)-adrenergic agonists has deleterious effects on cardiac muscle structure and function, the aim of the present study was to determine whether chronic clenbuterol administration would reduce the exercise capabilities of rats subjected to long-term treadmill sprint running, endurance swimming or voluntary wheel running training. The effect of clenbuterol treatment on exercise performance in rats was evaluated in three separate studies. Different groups of male rats were assigned to an endurance swimming (2 h/day, 5/7 days, 18 weeks) group, a treadmill sprint running (8x1 min bouts, 1.05 m/s, 20 weeks) group, or a voluntary wheel running (16 weeks) group. In each study, rats were allocated into either a treated group that received clenbuterol (2 mg.kg(-1).day(-1)) in their drinking water or an untreated control group. In each of the three studies, treated rats exhibited a reduction in exercise performance compared with untreated rats. Treated rats ran approximately 57% less total distance than untreated rats in the voluntary running programme and were unable to complete the swimming and sprinting protocols performed by the untreated rats. In each of the studies, the treated rats exhibited cardiac hypertrophy, with absolute heart mass increased by approximately 19% and heart mass relative to body mass increased by approximately 20%. The hearts of sedentary rats treated with clenbuterol exhibited extensive collagen infiltration surrounding blood vessels and in the wall of the left ventricle. The results indicate strongly that chronic clenbuterol administration deleteriously affects exercise performance in rats, potentially due to alterations in cardiac muscle structure and function.     

Assessment of muscle mass using ultrasound with minimal versus maximal pressure compared with computed tomography in critically ill adult patients

BackgroundPreserved skeletal muscle mass identified using computed tomography (CT) predicts improved outcomes from critical illness; however, CT imaging have few limitations such that it involves a radiation dose and transferring patients out of the intensive care unit. This study aimed to assess in critically ill patients the relationship between muscle mass estimates obtained using minimally invasive ultrasound techniques with both minimal and maximal pressure compared with CT images at the third lumber vertebra level.MethodsAll patients were treated in a single Australian intensive care unit. Eligible patients had paired assessments, within a 72-h window, of muscle mass by ultrasound (quadriceps muscle layer thickness in centimetres, with maximal and minimal pressure) and CT axial cross-sectional area (cm²). Data are presented as mean (standard deviation), median (interquartile range), and frequencies [n (%)].ResultsThirty-five patients [mean (standard deviation) age = 55 (16) years, median (interquartile range) body mass index = 27 (25–32) kg/m², and 26 (74%) men] contributed 41 paired measurements. Quadriceps muscle thickness measured using the maximal pressure technique was a strong independent predictor of lumbar muscle cross-sectional area. Within a multivariate mixed linear regression model and adjusting for sex, age, and body mass index, for every 1 cm increase in quadriceps muscle layer thickness, the lumbar muscle cross-sectional area increased by 35 cm² (95% confidence interval = 11–59 cm²). Similar univariate associations were observed using minimal pressure; however, as per multivariate analysis, there was no strength in this relationship [8 cm² (95% confidence interval = –5 to 22 cm²)].ConclusionUltrasound assessment of the quadriceps muscle using maximal pressure reasonably predicts the skeletal muscle at the third lumbar vertebra level of critically ill patients. However, there is substantial uncertainty within these regression estimates, and this may reduce the current utility of this technique as a minimally invasive surrogate for CT assessment of skeletal muscle mass.     

Nonthermal ultrasound and exercise in skeletal muscle regeneration

OBJECTIVE: To determine whether continuous nonthermal therapeutic ultrasound (US) and low-intensity exercise (Ex) influence skeletal muscle regeneration after a standardized contusion injury in an animal model. DESIGN: Randomized controlled trial with blinded comparisons in a 2 x 2 factorial (US by Ex) design. SETTING: Animal care facility and exercise physiology biochemistry laboratory. ANIMALS: Twenty male Wistar rats (age, 8 mo) received a reproducible bilateral contusion injury to the gastrocnemius muscles. Ten gastrocnemius muscles from 5 noninjured, nontreated rats provided baseline control data. INTERVENTIONS: US (continuous duty cycle, 3 MHz; intensity, 0.1 W/cm2 ; transducer, 1cm2 ; duration, 5 min/d; duty cycle, 100%) and exercise (20 min/d of low-intensity treadmill walking at 14 m/min). Gastrocnemius muscles from injured rats received exercise treatment alone (Ex + NoUS), exercise and US treatment (Ex + US), US treatment alone (NoEx + US), and no treatment (NoEx + NoUS). MAIN OUTCOME MEASURES: Ninety-six-hour postinjury muscle mass, contractile protein concentration, fiber cross-sectional area, number of nuclei per fiber, and myonuclear density. RESULTS: Myonuclei per fiber were statistically greater in injured than in noninjured gastrocnemius muscle (P < .05). There were no statistical differences (P > .01) among the 4 injured treatment groups for any of the outcome measures chosen as biomarkers of skeletal muscle regeneration. CONCLUSIONS: There is no evidence that the specific continuous US and Ex protocols investigated enhanced skeletal muscle regeneration after contusion injury.     

Effect of injecting primary myoblasts versus putative muscle-derived stem cells on mass and force generation in mdx mice

It is well established that the injection of normal myoblasts or of muscle-derived stem cells (MDSCs) into the muscle of dystrophin-deficient mdx mice results in the incorporation of a number of donor myoblasts into the host muscle. However, the effect of the injected exogenous cells on mdx muscle mass and functional capacity has not been evaluated. This study evaluates the mass and functional capacity of the extensor digitorum longus (EDL) muscles of adult, male mdx mice that received intramuscular injections of primary myoblasts or of MDSCs (isolated by a preplating technique; Qu, Z., Balkir, L., van Deutekom, J.C., Robbins, P.D., Pruchnic, R., and Huard, J., J. Cell Biol. 1998;142:1257-1267) derived from normal mice. Evaluations were made 9 weeks after cell transplantation. Uninjected mdx EDL muscles have a mass 50% greater than that of age-matched C57BL/10J (normal) EDL muscles. Injections of either primary myoblasts or MDSCs have no effect on the mass of mdx EDL muscles. EDL muscles of mdx mice generate 43% more absolute twitch tension and 43% less specific tetanic tension then do EDL muscles of C57BL/10J mice. However, the absolute tetanic and specific twitch tension of mdx and C57BL/10J EDL muscles are similar. Injection of either primary myoblasts or MDSCs has no effect on the absolute or specific twitch and tetanic tensions of mdx muscle. Approximately 25% of the myofibers in mdx EDL muscles that received primary myoblasts react positively with antibody to dystrophin. There is no significant difference in the number of dystrophin-positive myofibers when MDSCs are injected. Regardless of the source of donor cells, dystrophin is limited to short distances (60-900 microm) along the length of the myofibers. This may, in part, explain the failure of cellular therapy to alter the contractile properties of murine dystrophic muscle.     

Age-related reductions in appendicular skeletal muscle mass: association with habitual aerobic exercise status

Appendicular skeletal muscle mass decreases with advancing age, and this is thought to be a key factor for reductions in functional independence in the elderly. We determined the potential modulatory influence of regular aerobic exercise on the age-related reductions in appendicular muscle mass. In the present cross-sectional study, we studied a total of 131 healthy men aged 20-79 years. For at least the previous 2 years subjects were either sedentary or endurance-trained. Appendicular skeletal muscle mass was measured using dual-energy X-ray absorptiometry. There were no significant group differences in height. Body mass and body surface area were lower in endurance-trained compared with sedentary men (P<0.05). In general, body fat increased with age in both groups, but was lower in endurance-trained compared with sedentary men at any age group (P<0.05). Lean body mass and maximal oxygen consumption decreased with age (P<0.05). Irrespective of expression (absolute, relative to body surface area, or relative to body mass), arm, leg, and total limb muscle mass generally decreased with age. Absolute appendicular muscle mass was not different between the two activity groups. When expressed relative to body mass or body surface area, appendicular muscle mass in the endurance-trained middle-aged and older men was significantly higher than their sedentary peers. The rate of decline in appendicular muscle mass with age was similar between the two activity groups. The results of the present cross-sectional study indicate that endurance-trained men had significantly higher appendicular skeletal muscle mass relative to body mass or body size compared with their sedentary peers. This may contribute, at least in part, to the lower incidence of functional disability observed in middle-aged and older men who exercise regularly.     

beta(2)-Adrenergic stimulation attenuates left ventricular remodeling, decreases apoptosis, and improves calcium homeostasis in a rodent model of ischemic cardiomyopathy

The benefit of the beta(2)-adrenergic agonist, clenbuterol, in left ventricular assist device patients with dilated cardiomyopathy has been reported, but its effect on ischemic heart failure (HF) is unknown. We investigated whether clenbuterol improves left ventricular remodeling, myocardial apoptosis and has synergy with a beta(1) antagonist, metoprolol, in a model of ischemic HF. Rats were randomized to: 1) HF only; 2) HF + clenbuterol; 3) HF + metoprolol; 4) HF + clenbuterol + metoprolol; and 5) rats with sham surgery. HF was induced by left anterior descending artery (LAD) artery ligation and confirmed by decreased left ventricular fractional shortening, decreased maximum left ventricular dP/dt (dP/dt(max)), and elevated left ventricular end-diastolic pressure (LVEDP) compared with sham rats (p < 0.01). After 9 weeks of oral therapy, echocardiographic, hemodynamic, and ex vivo end-diastolic pressure-volume relationship (EDPVR) measurements were obtained. Immunohistochemistry was performed for myocardial apoptosis and DNA damage markers. Levels of calcium-handling proteins were assessed by Western blot analysis. Clenbuterol-treated HF rats had increased weight gain and heart weights versus HF rats (p < 0.05). EDPVR curves revealed a leftward shift in clenbuterol rats versus metoprolol and HF rats (p < 0.05). The metoprolol-treated group had a lower LVEDP and higher dP/dt(max) versus the HF group (p < 0.05). Clenbuterol and metoprolol groups had decreased myocardial apoptosis and DNA damage markers and increased DNA repair markers versus HF rats (all p < 0.01). Protein levels of the ryanodine receptor and sarcoplasmic reticulum calcium-ATPase were improved in clenbuterol-, metoprolol-, and clenbuterol+metoprolol-treated groups versus HF rats. However, as a combination therapy, there were no synergistic effects of clenbuterol+metoprolol treatment. We conclude that clenbuterol ameliorates EDPVR, apoptosis, and calcium homeostasis but does not have synergy with metoprolol in our model of ischemic HF.