Objective-To determine the relation of hamstring and quadriceps muscle strength and imbalance to hamstring injury using a prospective observational cohort study Method-A total of 102 senior male Australian Rules footballers aged 22.2 (3.6) years were tested at the start of a football season. Maximum voluntary concentric and eccentric torque of the hamstring and quadriceps muscles of both legs was assessed using a Kin-Com isokinetic dynamometer at angular velocities of 60 and 180 degrees/second. Twelve (11.8%) players sustained clinically diagnosed hamstring strains which caused them to miss one or more matches over the ensuing season. Results-There were no significant diVerences for any of the isokinetic variables comparing the injured and non-injured legs in players with unilateral hamstring strains (n = 9). Neither the injured nor the non-injured leg of injured players diVered from the mean of left and right legs in non-injured players for any isokinetic variable. The hamstring to opposite hamstring ratios also did not diVer between injured and non-injured players. A hamstring to opposite hamstring ratio of less than 0.90 and a hamstring to quadriceps ratio of less than 0.60 were not associated with an increased risk of hamstring injury. A significantly greater percentage of players who sustained a hamstring strain reported a history of hamstring strain compared with non-injured players (p = 0.02). However, this was not related to muscle weakness or imbalance. Conclusions-Isokinetic muscle strength testing was not able to directly discriminate Australian Rules football players at risk for a hamstring injury. (Br J Sports Med 1998;32:309-314)

To identify mechanisms of anabolic androgen action in muscle, we generated male and female genomic androgen receptor (AR) knockout (ARKO) mice, and characterized muscle mass, contractile function, and gene expression. Muscle mass is decreased in ARKO males, but normal in ARKO females. The levator ani muscle, which fails to develop in normal females, is also absent in ARKO males. Force production is decreased from fast-twitch ARKO male muscle, and slow-twitch muscle has increased fatigue resistance. Microarray analysis shows up-regulation of genes encoding slow-twitch muscle contractile proteins. Real-time PCR confirms that expression of genes encoding polyamine biosynthetic enzymes, ornithine decarboxylase (Odc1), and S-adenosylmethionine decarboxylase (Amd1), is reduced in ARKO muscle, suggesting androgens act through regulation of polyamine biosynthesis. Altered expression of regulators of myoblast progression from proliferation to terminal differentiation suggests androgens also promote muscle growth by maintaining myoblasts in the proliferate state and delaying differentiation (increased Cdkn1c and Igf2, decreased Itg1bp3). A similar pattern of gene expression is observed in orchidectomized male mice, during androgen withdrawal-dependent muscle atrophy. In conclusion, androgens are not required for peak muscle mass in females. In males, androgens act through the AR to regulate multiple gene pathways that control muscle mass, strength, and fatigue resistance.

The beta2-adrenoceptor agonist (beta2-agonist) fenoterol has potent anabolic effects on rat skeletal muscle. We conducted an extensive dose-response study to determine the most efficacious dose of fenoterol for increasing skeletal muscle mass in adult rats and used this dose in testing the hypothesis that fenoterol may have therapeutic potential for ameliorating age-related muscle wasting and weakness. We used adult (16-month-old) rats that had completed their growth and development, and old (28-month-old) rats that exhibited characteristic muscle wasting and weakness, and treated them daily with either fenoterol (1.4 mg kg(-1), i.p), or saline vehicle, for 4 weeks. Following treatment, functional characteristics of fast-twitch extensor digitorum longus (EDL) and predominantly slow-twitch soleus muscles of the hindlimb were assessed in vitro. Untreated old rats exhibited a loss of skeletal muscle mass and a decrease in force-producing capacity, in both fast and slow muscles, compared with adult rats (P < 0.05). However, there was no age-associated decrease in skeletal muscle beta-adrenoceptor density, nor was the muscle response to chronic beta-agonist stimulation reduced with age. Thus, muscle mass and force-producing capacity of EDL and soleus muscles from old rats treated with fenoterol was equivalent to, or greater than, untreated adult rats. The increase in mass and strength was attributed to a non-selective increase in the cross-sectional area of all muscle fibre types, in both the EDL and soleus. Fenoterol treatment caused a small increase in fatiguability due to a decrease in oxidative metabolism in both EDL and soleus muscles, with some cardiac hypertrophy. Further studies are needed to fully separate the desirable effects on skeletal muscle and the undesirable effects on the heart. Nevertheless, our results demonstrate that fenoterol is a powerful anabolic agent that can restore muscle mass and strength in old rats, and provide preliminary evidence of therapeutic potential for age-related muscle wasting and weakness.

. ␤2-Agonist fenoterol has greater effects on contractile function of rat skeletal muscles than clenbuterol. Am J Physiol Regul Integr Comp Physiol 283: R1386-R1394, 2002. First published September 5, 2002 10.1152/ajpregu.00324.2002-Potential treatments for skeletal muscle wasting and weakness ideally possess both anabolic and ergogenic properties. Although the ␤2-adrenoceptor agonist clenbuterol has well-characterized effects on skeletal muscle, less is known about the therapeutic potential of the related ␤2-adrenoceptor agonist fenoterol. We administered an equimolar dose of either clenbuterol or fenoterol to rats for 4 wk to compare their effects on skeletal muscle and tested the hypothesis that fenoterol would produce more powerful anabolic and ergogenic effects. Clenbuterol treatment increased fiber cross-sectional area (CSA) by 6% and maximal isometric force (Po) by 20% in extensor digitorum longus (EDL) muscles, whereas fiber CSA in soleus muscles decreased by 3% and Po was unchanged, compared with untreated controls. In the EDL muscles, fenoterol treatment increased fiber CSA by 20% and increased Po by 12% above values achieved after clenbuterol treatment. Soleus muscles of fenoterol-treated rats exhibited a 13% increase in fiber CSA and a 17% increase in Po above that of clenbuteroltreated rats. These data indicate that fenoterol has greater effects on the functional properties of rat skeletal muscles than clenbuterol.

Limited knowledge exists regarding the efficacy of insulin-like growth factor I (IGF-I) administration as a therapeutic intervention for muscular dystrophies, although findings from other muscle pathology models suggest clinical potential. The diaphragm muscles of mdx mice (a model for Duchenne muscular dystrophy) were examined after 8 weeks of IGF-I administration (1 mg/kg s.c.) to test the hypothesis that IGF-I would improve the functional properties of dystrophic skeletal muscles. Force per cross-sectional area was ϳ49% greater in the muscles of treated mdx mice (149.6 ؎ 9.6 kN/m 2 ) compared with untreated mice (100.1 ؎ 4.6 kN/m 2 , P < 0.05), and maintenance of force over repeated maximal contraction was enhanced ϳ30% in muscles of treated mice (P < 0.05). Diaphragm muscles from treated mice comprised fibers with ϳ36% elevated activity of the oxidative enzyme succinate dehydrogenase, and ϳ23% reduction in the proportion of fast IId/x muscle fibers with concomitant increase in the proportion of type IIa fibers compared with untreated mice (P < 0.05). The data demonstrate that IGF-I administration can enhance the fatigue resistance of respiratory muscles in an animal model of dystrophin deficiency, in conjunction with enhancing energenic enzyme activity. As respiratory function is a mortality predictor in Duchenne muscular dystrophy patients, further evaluation of IGF-I intervention is recommended. (Am J

. Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice. Am J Physiol Endocrinol Metab 291: E506 -E516, 2006. First published April 18, 2006 doi:10.1152/ajpendo.00058.2006.-Androgens promote anabolism in skeletal muscle; however, effects on subsequent muscle function are less well defined because of a lack of reliable experimental models. We established a rigorous model of androgen withdrawal and administration in male mice and assessed androgen regulation of muscle mass, structure, and function. Adult C57Bl/6J male mice were orchidectomized (Orx) or sham-operated (Sham) and received 10 wk of continuous testosterone (T) or control treatment (C) via intraperitoneal implants. Mass, fiber cross-sectional area (CSA), and in vitro contractile function were assessed for fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles. After 10 wk, OrxϩC mice had reduced body weight gain (P Ͻ 0.05), seminal vesicle mass (P Ͻ 0.01), and levator ani muscle mass (P Ͻ 0.001) compared with ShamϩC mice, and these effects were prevented with testosterone treatment. OrxϩT mice had greater EDL (P Ͻ 0.01) and SOL (P Ͻ 0.01) muscle mass compared with OrxϩC mice; however, median fiber CSA was not significantly altered in these muscles. EDL and SOL muscle force was greater in ShamϩT compared with OrxϩC mice (P Ͻ 0.05) in proportion to muscle mass. Unexpectedly, OrxϩT mice had increased fatigue resistance of SOL muscle compared with OrxϩC mice (P Ͻ 0.001). We used a rigorous model of androgen withdrawal and administration in male mice to demonstrate an essential role of androgens in the maintenance of muscle mass and force. In addition, we showed that testosterone treatment increases resistance to fatigue of slow-but not fast-twitch muscle. contractile function; force; androgen receptor RECENT WELL-CONTROLLED, double-blinded studies have demonstrated unequivocally that androgens regulate muscle mass in humans (29); however, the effect of androgens on subsequent muscle strength is less clear. Anecdotal evidence of muscle anabolism and enhanced physical performance in steroid-using athletes suggests that increased muscle bulk is explicitly linked to enhanced muscle function (66). To date, this premise remains unsubstantiated because of contradictory reports of the effect of androgens on muscle force-producing capacity in both human and animal studies.In humans, there is clear evidence that physiological testosterone administration increases lean body mass in conditions of low circulating androgens. Testosterone replacement therapy has been effectively used to counteract loss of lean body mass in hypogonadal men (4, 11, 32), older men with normal or low serum testosterone (21, 54), and human immunodeficiency virus (HIV)-infected men with low serum testosterone (2). Similarly, muscle anabolism has been achieved in eugonadal states following supraphysiological administration to young, healthy men (3, 25) and in HIV-infected men with normal ...

Intramuscular injection of naked plasmid DNA is a less cytotoxic alternative to viral vectors for delivering genetic material to skeletal muscle in vivo. However, the low efficiency of plasmid-based gene transfer limits its potential therapeutic efficacy and/or its use for many experimental applications. Current strategies to enhance transfection efficiency (i.e., electroporation) can cause significant muscle damage, confounding physiological assessments such as muscle contractility. Optimizing protocols to limit damage is critical for accurate physiological, biochemical, and molecular measurements. Following extensive testing, we developed an electroporation protocol that enhances transfection efficiency in skeletal muscles without causing muscle damage. Pretreating mouse tibialis anterior muscles with hyaluronidase and electroporation at 75 V/cm (using 50% vol/vol saline as a vehicle for plasmid DNA) resulted in 22 +/- 5% of the muscle fibers expressing a reporter gene. This protocol did not compromise contractile function of skeletal muscles assessed at both the intact (whole) muscle and the cellular (single fiber) level. Furthermore, ectopic expression of insulin-like growth factor I to levels that induced muscle fiber hypertrophy without causing tissue damage or compromising muscle function highlights the therapeutic potential of these methods for myopathies, muscle wasting disorders, and other pathophysiologic conditions.

Beta(2)-adrenoceptor agonists such as fenoterol are anabolic in skeletal muscle, and because they promote hypertrophy and improve force-producing capacity, they have potential application for enhancing muscle repair after injury. No previous studies have measured the beta(2)-adrenoceptor population in regenerating skeletal muscle or determined whether fenoterol can improve functional recovery in regenerating muscle after myotoxic injury. In the present study, the extensor digitorum longus (EDL) muscle of the right hindlimb of deeply anesthetized rats was injected with bupivacaine hydrochloride, which caused complete degeneration of all muscle fibers. The EDL muscle of the left hindlimb served as the uninjured control. Rats received either fenoterol (1.4 mg x kg(-1) x day(-1)) or an equal volume of saline for 2, 7, 14, or 21 days. Radioligand binding assays identified a approximately 3.5-fold increase in beta(2)-adrenoceptor density in regenerating muscle at 2 days postinjury. Isometric contractile properties of rat EDL muscles were measured in vitro. At 14 and 21 days postinjury, maximum force production (P(o)) of injured muscles from fenoterol-treated rats was 19 and 18% greater than from saline-treated rats, respectively, indicating more rapid restoration of function after injury. The increase in P(o) in fenoterol-treated rats was due to increases in muscle mass, fiber cross-sectional area, and protein content. These findings suggest a physiological role for beta(2)-adrenoceptor-mediated mechanisms in muscle regeneration and show clearly that fenoterol hastens recovery after injury, indicating its potential therapeutic application.