Monitoring the Health Status of Mice with Bleomycin-induced Lung Injury by Using Body Condition Scoring.

Well-defined, humane endpoints aid in monitoring animal health status during disease development. Body condition scoring (BCS) is a method for assessing health status in mouse studies where wasting and death are potential endpoints. Whether BCS is useful in monitoring animals with bleomycin-induced lung injury has not been reported. Body weight (BW) is a common humane endpoint for this model, but because the lungs increase in weight as BW decreases, the animal's true physical condition could be masked when using BW as the sole endpoint criterion. Therefore, our goal here was to assess the usefulness of BCS in monitoring health status in a mouse model of lung injury. Lung injury was caused by acute instil- lation of the fibrogenic antibiotic bleomycin into the lungs through the trachea. Male C57BL/6 mice received bleomycin (0.075 U) dissolved in saline or saline alone. Bleomycin instillation led to a doubling of lung weight and decreases in both BW and BCS, compared with saline instillation. The changes in BW and BCS were significantly correlated with lung weight. When the adjusted BW was used (corrected for the increase in lung weight), the correlation was unchanged, suggesting that the increase in lung weight did not significantly mask the decrease in BW. Bleomycin instillation caused decreases in both soleus and visceral epididymal fat masses. The change in BCS was significantly correlated with both soleus and VEF mass, suggesting that BCS is reflective of the systemic loss of muscle and fat mass. Our findings suggest that BW and BCS are significantly correlated to lung injury in the bleomycin model of lung fibrosis and that BCS is an appropriate alternative humane endpoint in this mouse model.

Reversal of right ventricular failure by chronic α1A-subtype adrenergic agonist therapy.

Right ventricular (RV) failure (RVF) is a serious disease with no effective treatment available. We recently reported a disease prevention study showing that chronic stimulation of α1A-adrenergic receptors (α1A-ARs), started at the time of RV injury, prevented the development of RVF. The present study used a clinically relevant disease reversal design to test if chronic α1A-AR stimulation, started after RVF was established, could reverse RVF. RVF was induced surgically by pulmonary artery constriction in mice. Two weeks after pulmonary artery constriction, in vivo RV fractional shortening as assessed by MRI was reduced by half relative to sham-operated controls (25 ± 2%, n = 27, vs. 52 ± 2%, n = 13, P < 10-11). Subsequent chronic treatment with the α1A-AR agonist A61603 for a further 2 wk resulted in a substantial recovery of RV fractional shortening (to 41 ± 2%, n = 17, P < 10-7 by a paired t-test) along with recovery of voluntary exercise capacity. Mechanistically, chronic A61603 treatment resulted in increased activation of the prosurvival kinase ERK, increased abundance of the antiapoptosis factor Bcl-2, and decreased myocyte necrosis evidenced by a decreased serum level of cardiac troponin. Moreover, A61603 treatment caused increased abundance of the antioxidant glutathione peroxidase-1, decreased level of reactive oxygen species, and decreased oxidative modification (carbonylation) of myofilament proteins. Consistent with these effects, A61603 treatment resulted in increased force development by cardiac myofilaments, which might have contributed to increased RV function. These findings suggest that the α1A-AR is a therapeutic target to reverse established RVF. NEW & NOTEWORTHY Currently, there are no effective therapies for right ventricular (RV) failure (RVF). This project evaluated a novel therapy for RVF. In a mouse model of RVF, chronic stimulation of α1A-adrenergic receptors with the agonist A61603 resulted in recovery of in vivo RV function, improved exercise capacity, reduced oxidative stress-related carbonylation of contractile proteins, and increased myofilament force generation. These results suggest that the α1A-adrenergic receptor is a therapeutic target to treat RVF.

α1A-Subtype adrenergic agonist therapy for the failing right ventricle.

Failure of the right ventricle (RV) is a serious disease with a poor prognosis and limited treatment options. Signaling by α1-adrenergic receptors (α1-ARs), in particular the α1A-subtype, mediate cardioprotective effects in multiple heart failure models. Recent studies have shown that chronic treatment with the α1A-subtype agonist A61603 improves function and survival in a model of left ventricular failure. The goal of the present study was to determine if chronic A61603 treatment is beneficial in a RV failure model. We used tracheal instillation of the fibrogenic antibiotic bleomycin in mice to induce pulmonary fibrosis, pulmonary hypertension, and RV failure within 2 wk. Some mice were chronically treated with a low dose of A61603 (10 ng·kg-1·day-1). In the bleomycin model of RV failure, chronic A61603 treatment was associated with improved RV fractional shortening and greater in vitro force development by RV muscle preparations. Cell injury markers were reduced with A61603 treatment (serum cardiac troponin I, RV fibrosis, and expression of matrix metalloproteinase-2). RV oxidative stress was reduced (using the probes dihydroethidium and 4-hydroxynonenal). Consistent with lowered RV oxidative stress, A61603 was associated with an increased level of the cellular antioxidant superoxide dismutase 1 and a lower level of the prooxidant NAD(P)H oxidase isoform NOX4. In summary, in the bleomycin model of RV failure, chronic A61603 treatment reduced RV oxidative stress, RV myocyte necrosis, and RV fibrosis and increased both RV function and in vitro force development. These findings suggest that in the context of pulmonary fibrosis, the α1A-subtype is a potential therapeutic target to treat the failing RV.NEW & NOTEWORTHY Right ventricular (RV) failure is a serious disease with a poor prognosis and no effective treatments. In the mouse bleomycin model of RV failure, we tested the efficacy of a treatment using the α1A-adrenergic receptor subtype agonist A61603. Chronic A61603 treatment improved RV contraction and reduced multiple indexes of RV injury, suggesting that the α1A-subtype is a therapeutic target to treat RV failure.

Oxidant production and SOD1 protein expression in single skeletal myofibers from Down syndrome mice.

Down syndrome (DS) is a genetic condition caused by the triplication of chromosome 21. Persons with DS exhibit pronounced muscle weakness, which also occurs in the Ts65Dn mouse model of DS. Oxidative stress is thought to be an underlying factor in the development of DS-related pathologies including muscle dysfunction. High-levels of oxidative stress have been attributed to triplication and elevated expression of superoxide dismutase 1 (SOD1); a gene located on chromosome 21. The elevated expression of SOD1 is postulated to increase production of hydrogen peroxide and cause oxidative injury and cell death. However, it is unknown whether SOD1 protein expression is associated with greater oxidant production in skeletal muscle from Ts65Dn mice. Thus, our objective was to assess levels of SOD1 expression and oxidant production in skeletal myofibers from the flexor digitorum brevis obtained from Ts65Dn and control mice. Measurements of oxidant production were obtained from myofibers loaded with 2',7'-dichlorodihydrofluorescein diacetate (DCFH2-DA) in the basal state and following 15min of stimulated unloaded contraction. Ts65Dn myofibers exhibited a significant decrease in basal DCF emissions (p < 0.05) that was associated with an approximate 3-fold increase in SOD1 (p < 0.05). DCF emissions were not affected by stimulating contraction of Ts65Dn or wild-type myofibers (p > 0.05). Myofibers from Ts65Dn mice tended to be smaller and myonuclear domain was lower (p < 0.05). In summary, myofibers from Ts65Dn mice exhibited decreased basal DCF emissions that were coupled with elevated protein expression of SOD1. Stimulated contraction in isolated myofibers did not affect DCF emissions in either group. These findings suggest the skeletal muscle dysfunction in the adult Ts65Dn mouse is not associated with skeletal muscle oxidative stress.

Hyperpolarized 13 C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model.

Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) 13 C dehydroascorbate (DHA) and 13 C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI). Compared with the contralateral sham-operated kidneys, the kidneys subjected to IRI showed a significant decrease in the HP 13 C vitamin C/(vitamin C + DHA) ratio, consistent with a decrease in redox capacity. The kidneys subjected to IRI also showed a significant decrease in the HP 13 C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP 13 C lactate/pyruvate ratio at day 7 compared with baseline, although the 13 C lactate/pyruvate ratio was not significantly different between the IRI and contralateral sham-operated kidneys at day 7. Arterial spin labeling magnetic resonance imaging (MRI) demonstrated significantly reduced perfusion in the IRI kidneys. Renal tissue analysis showed corresponding increased reactive oxygen species (ROS) and reduced PDH activity in the IRI kidneys. Our results show the feasibility of HP 13 C MRS for the non-invasive assessment of oxidative stress and mitochondrial PDH activity following renal IRI.

An intracellular matrix metalloproteinase-2 isoform induces tubular regulated necrosis: implications for acute kidney injury.

Acute kidney injury (AKI) causes severe morbidity, mortality, and chronic kidney disease (CKD). Mortality is particularly marked in the elderly and with preexisting CKD. Oxidative stress is a common theme in models of AKI induced by ischemia-reperfusion (I-R) injury. We recently characterized an intracellular isoform of matrix metalloproteinase-2 (MMP-2) induced by oxidative stress-mediated activation of an alternate promoter in the first intron of the MMP-2 gene. This generates an NH2-terminal truncated MMP-2 (NTT-MMP-2) isoform that is intracellular and associated with mitochondria. The NTT-MMP-2 isoform is expressed in kidneys of 14-mo-old mice and in a mouse model of coronary atherosclerosis and heart failure with CKD. We recently determined that NTT-MMP-2 is induced in human renal transplants with delayed graft function and correlated with tubular cell necrosis. To determine mechanism(s) of action, we generated proximal tubule cell-specific NTT-MMP-2 transgenic mice. Although morphologically normal at the light microscopic level at 4 mo, ultrastructural studies revealed foci of tubular epithelial cell necrosis, the mitochondrial permeability transition, and mitophagy. To determine whether NTT-MMP-2 expression enhances sensitivity to I-R injury, we performed unilateral I-R to induce mild tubular injury in wild-type mice. In contrast, expression of the NTT-MMP-2 isoform resulted in a dramatic increase in tubular cell necrosis, inflammation, and fibrosis. NTT-MMP-2 mice had enhanced expression of innate immunity genes and release of danger-associated molecular pattern molecules. We conclude that NTT-MMP-2 "primes" the kidney to enhanced susceptibility to I-R injury via induction of mitochondrial dysfunction. NTT-MMP-2 may be a novel AKI treatment target.

Adrenergic Receptors in Individual Ventricular Myocytes: The Beta-1 and Alpha-1B Are in All Cells, the Alpha-1A Is in a Subpopulation, and the Beta-2 and Beta-3 Are Mostly Absent.

RATIONALE: It is unknown whether every ventricular myocyte expresses all 5 of the cardiac adrenergic receptors (ARs), ß1, ß2, ß3, α1A, and α1B. The ß1 and ß2 are thought to be the dominant myocyte ARs. OBJECTIVE: Quantify the 5 cardiac ARs in individual ventricular myocytes. METHODS AND RESULTS: We studied ventricular myocytes from wild-type mice, mice with α1A and α1B knockin reporters, and ß1 and ß2 knockout mice. Using individual isolated cells, we measured knockin reporters, mRNAs, signaling (phosphorylation of extracellular signal-regulated kinase and phospholamban), and contraction. We found that the ß1 and α1B were present in all myocytes. The α1A was present in 60%, with high levels in 20%. The ß2 and ß3 were detected in only ≈5% of myocytes, mostly in different cells. In intact heart, 30% of total ß-ARs were ß2 and 20% were ß3, both mainly in nonmyocytes. CONCLUSION: The dominant ventricular myocyte ARs present in all cells are the ß1 and α1B. The ß2 and ß3 are mostly absent in myocytes but are abundant in nonmyocytes. The α1A is in just over half of cells, but only 20% have high levels. Four distinct myocyte AR phenotypes are defined: 30% of cells with ß1 and α1B only; 60% that also have the α1A; and 5% each that also have the ß2 or ß3. The results raise cautions in experimental design, such as receptor overexpression in myocytes that do not express the AR normally. The data suggest new paradigms in cardiac adrenergic signaling mechanisms.

The Alpha-1A Adrenergic Receptor in the Rabbit Heart.

The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 µg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 µg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse.

The α1A-adrenergic receptor subtype mediates increased contraction of failing right ventricular myocardium.

Dysfunction of the right ventricle (RV) is closely related to prognosis for patients with RV failure. Therefore, strategies to improve failing RV function are significant. In a mouse RV failure model, we previously reported that α1-adrenergic receptor (α1-AR) inotropic responses are increased. The present study determined the roles of both predominant cardiac α1-AR subtypes (α1A and α1B) in upregulated inotropy in failing RV. We used the mouse model of bleomycin-induced pulmonary fibrosis, pulmonary hypertension, and RV failure. We assessed the myocardial contractile response in vitro to stimulation of the α1A-subtype (using α1A-subtype-selective agonist A61603) and α1B-subtype [using α1A-subtype knockout mice and nonsubtype selective α1-AR agonist phenylephrine (PE)]. In wild-type nonfailing RV, a negative inotropic effect of α1-AR stimulation with PE (force decreased ≈50%) was switched to a positive inotropic effect (PIE) with bleomycin-induced RV injury. Upregulated inotropy in failing RV occurred with α1A-subtype stimulation (force increased ≈200%), but not with α1B-subtype stimulation (force decreased ≈50%). Upregulated inotropy mediated by the α1A-subtype involved increased activator Ca(2+) transients and increased phosphorylation of myosin regulatory light chain (a mediator of increased myofilament Ca(2+) sensitivity). In failing RV, the PIE elicited by the α1A-subtype was appreciably less when the α1A-subtype was stimulated in combination with the α1B-subtype, suggesting functional antagonism between α1A- and α1B-subtypes. In conclusion, upregulation of α1-AR inotropy in failing RV myocardium requires the α1A-subtype and is opposed by the α1B-subtype. The α1A subtype might be a therapeutic target to improve the function of the failing RV.

Constitutive phosphorylation of cardiac myosin regulatory light chain in vivo.

In beating hearts, phosphorylation of myosin regulatory light chain (RLC) at a single site to 0.45 mol of phosphate/mol by cardiac myosin light chain kinase (cMLCK) increases Ca(2+) sensitivity of myofilament contraction necessary for normal cardiac performance. Reduction of RLC phosphorylation in conditional cMLCK knock-out mice caused cardiac dilation and loss of cardiac performance by 1 week, as shown by increased left ventricular internal diameter at end-diastole and decreased fractional shortening. Decreased RLC phosphorylation by conventional or conditional cMLCK gene ablation did not affect troponin-I or myosin-binding protein-C phosphorylation in vivo. The extent of RLC phosphorylation was not changed by prolonged infusion of dobutamine or treatment with a ß-adrenergic antagonist, suggesting that RLC is constitutively phosphorylated to maintain cardiac performance. Biochemical studies with myofilaments showed that RLC phosphorylation up to 90% was a random process. RLC is slowly dephosphorylated in both noncontracting hearts and isolated cardiac myocytes from adult mice. Electrically paced ventricular trabeculae restored RLC phosphorylation, which was increased to 0.91 mol of phosphate/mol of RLC with inhibition of myosin light chain phosphatase (MLCP). The two RLCs in each myosin appear to be readily available for phosphorylation by a soluble cMLCK, but MLCP activity limits the amount of constitutive RLC phosphorylation. MLCP with its regulatory subunit MYPT2 bound tightly to myofilaments was constitutively phosphorylated in beating hearts at a site that inhibits MLCP activity. Thus, the constitutive RLC phosphorylation is limited physiologically by low cMLCK activity in balance with low MLCP activity.

Aging-related changes in the iron status of skeletal muscle.

The rise in non-heme iron (NHI) concentration observed in skeletal muscle of aging rodents is thought to contribute to the development of sarcopenia. The source of the NHI has not been identified, nor have the physiological ramifications of elevated iron status in aged muscle been directly examined. Therefore, we assessed plantaris NHI and heme iron (HI) levels in addition to expression of proteins involved in iron uptake (transferrin receptor-1; TfR1), storage (ferritin), export (ferroportin; FPN), and regulation (iron regulatory protein-1 (IRP1) and -2 (IRP2)) of male F344xBN F1 rats (n=10/group) of various ages (8, 18, 28, 32, and 36 months) to further understand iron regulation in aging muscle. In a separate experiment, iron chelator (pyridoxal isonicotinoyl hydrazone; PIH) or vehicle was administered to male F344xBN F1 rats (n=8/group) beginning at 30 months of age to assess the impact on plantaris muscle mass and function at ~36 months of age. Principle findings revealed the increased NHI concentration in old age was consistent with concentrating effects of muscle atrophy and reduction in HI levels, with no change in the total iron content of the muscle. The greatest increase in muscle iron content occurred during the period of animal growth and was associated with downregulation of TfR1 and IRP2 expression. Ferritin upregulation did not occur until senescence and the protein remained undetectable during the period of muscle iron content elevation. Lastly, administration of PIH did not significantly (p>0.05) impact NHI or measures of muscle atrophy or contractile function. In summary, this study confirms that the elevated NHI concentration in old age is largely due to the loss in muscle mass. The increased muscle iron content during aging does not appear to associate with cytosolic ferritin storage, but the functional consequences of elevated iron status in old age remains to be determined.

Functional and biochemical characterization of soleus muscle in Down syndrome mice: insight into the muscle dysfunction seen in the human condition.

Persons with Down syndrome (DS) exhibit low muscle strength that significantly impairs their physical functioning. The Ts65Dn mouse model of DS also exhibits muscle weakness in vivo and may be a useful model to examine DS-associated muscle dysfunction. Therefore, the purpose of this experiment was to directly assess skeletal muscle function in the Ts65Dn mouse and to reveal potential mechanisms of DS-associated muscle weakness. Soleus muscles were harvested from anesthetized male Ts65Dn and wild-type (WT) colony controls. In vitro muscle contractile experiments revealed normal force generation of nonfatigued Ts65Dn soleus, but a 12% reduction in force was observed during recovery from fatiguing contractions compared with WT muscle (P < 0.05). Indicators of oxidative stress and mitochondrial oxidative capacity were assessed to reveal potential mechanisms of DS-associated muscle weakness. Protein expression of copper-zinc superoxide dismutase (SOD1), a triplicated gene in persons with DS and Ts65Dn mice, was increased 25% (P < 0.05) in Ts65Dn soleus. Nontriplicated antioxidant protein expression was similar between groups. Lipid peroxidation was unaltered in Ts65Dn animals, but protein oxidation was 20% greater compared with controls (P < 0.05). Cytochrome-c oxidase expression was 22% lower in Ts65Dn muscle (P < 0.05), while expression of citrate synthase was similar between groups. Microarray analysis revealed alteration of numerous pathways in Ts65Dn muscle, including proteolysis, glucose and fat metabolism, neuromuscular transmission, and ATP biosynthesis. In summary, despite biochemical and gene expression differences in soleus muscle of Ts65Dn animals, the functional properties of skeletal muscle likely contribute a minor part to the in vivo muscle weakness.

The effect of progressive resistance training on leg strength, aerobic capacity and functional tasks of daily living in persons with Down syndrome.

PURPOSE: The purpose of this study was to examine the effect of progressive resistance training on leg strength, aerobic capacity and physical function in persons with Down syndrome (DS). METHOD: Thirty persons with DS (age 28 SD 8 years) were assigned to an intervention or control group. The intervention group performed resistance training 2 days per week for 10 weeks. Participants performed tests to measure isometric and isokinetic knee extensor and flexor peak torque, peak aerobic capacity and timed performance on chair rise, walking and stair ascent and descent. RESULT: Persons with DS receiving the intervention significantly increased their isokinetic knee extensor and flexor peak torque [Absolute change (post minus pre-value) was 17.0 SD 29.6 and 12.6 SD 18.9 N m, respectively] and isometric knee extensor peak torque at angles of 45° (2.9 SD 23.2 N m), 60° (3.0 SD 22.9 N m) and 75° (14.2 SD 30.0 N m). These changes were significantly greater than in the control group. In addition, the time to ascend (-0.3 SD 0.8 s) and descend (-0.6 SD 0.9 s) stairs significantly decreased in the intervention group compared to the control group. CONCLUSION: These findings show that progressive resistance training is an effective intervention for persons with DS to improve leg strength and stair-climbing ability.

The use of instability to train the core musculature.

Training of the trunk or core muscles for enhanced health, rehabilitation, and athletic performance has received renewed emphasis. Instability resistance exercises have become a popular means of training the core and improving balance. Whether instability resistance training is as, more, or less effective than traditional ground-based resistance training is not fully resolved. The purpose of this review is to address the effectiveness of instability resistance training for athletic, nonathletic, and rehabilitation conditioning. The anatomical core is defined as the axial skeleton and all soft tissues with a proximal attachment on the axial skeleton. Spinal stability is an interaction of passive and active muscle and neural subsystems. Training programs must prepare athletes for a wide variety of postures and external forces, and should include exercises with a destabilizing component. While unstable devices have been shown to be effective in decreasing the incidence of low back pain and increasing the sensory efficiency of soft tissues, they are not recommended as the primary exercises for hypertrophy, absolute strength, or power, especially in trained athletes. For athletes, ground-based free-weight exercises with moderate levels of instability should form the foundation of exercises to train the core musculature. Instability resistance exercises can play an important role in periodization and rehabilitation, and as alternative exercises for the recreationally active individual with less interest or access to ground-based free-weight exercises. Based on the relatively high proportion of type I fibers, the core musculature might respond well to multiple sets with high repetitions (e.g., >15 per set); however, a particular sport may necessitate fewer repetitions.

Canadian Society for Exercise Physiology position stand: The use of instability to train the core in athletic and nonathletic conditioning.

The use of instability devices and exercises to train the core musculature is an essential feature of many training centres and programs. It was the intent of this position stand to provide recommendations regarding the role of instability in resistance training programs designed to train the core musculature. The core is defined as the axial skeleton and all soft tissues with a proximal attachment originating on the axial skeleton, regardless of whether the soft tissue terminates on the axial or appendicular skeleton. Core stability can be achieved with a combination of muscle activation and intra-abdominal pressure. Abdominal bracing has been shown to be more effective than abdominal hollowing in optimizing spinal stability. When similar exercises are performed, core and limb muscle activation are reported to be higher under unstable conditions than under stable conditions. However, core muscle activation that is similar to or higher than that achieved in unstable conditions can also be achieved with ground-based free-weight exercises, such as Olympic lifts, squats, and dead lifts. Since the addition of unstable bases to resistance exercises can decrease force, power, velocity, and range of motion, they are not recommended as the primary training mode for athletic conditioning. However, the high muscle activation with the use of lower loads associated with instability resistance training suggests they can play an important role within a periodized training schedule, in rehabilitation programs, and for nonathletic individuals who prefer not to use ground-based free weights to achieve musculoskeletal health benefits.

Physical fitness predicts functional tasks in individuals with Down syndrome.

UNLABELLED: Individuals with Down syndrome (DS) exhibit reduced strength and aerobic capacity, which may limit their ability to perform functional tasks of daily living. PURPOSE: This study was conducted to examine the relationship between timed performance on functional tasks of daily living and age, knee isometric strength, and peak aerobic capacity in a group of individuals with DS. METHODS: This was a cross-sectional study involving 35 individuals (27 +/- 7.5 yr) with DS. Participants completed an isometric test of knee extensor and flexor strength, an individualized exercise test to measure peak aerobic capacity, and three timed functional tasks of daily living, which included chair rise, gait speed, and stair ascent and descent. Multiple regression analyses were performed to examine the relationship between timed task performance and age, knee isometric strength, and peak aerobic capacity. RESULTS: The multiple regression models explained 11-29% of the variance in timed task performance. Knee extensor strength was the most influential variable in predicting timed task performance (squared semipartial correlation coefficient [sr2] = 0.11-0.20), followed by aerobic capacity (sr2 = 0.10-0.14). Age was not a significant predictor of timed task performance. CONCLUSION: These findings suggest that physical fitness (defined here as aerobic capacity and knee extensor strength) limits the ability of adults with DS to perform functional tasks of daily living. Randomized controlled trials should be performed to test the probable causal relationship between exercises designed to improve physical fitness and functional tasks of daily living.

Age, weight, and the front abdominal power test as predictors of isokinetic trunk strength and work in young men and women.

First we tested the reliability of two new field tests of core stability (plank to fatigue test [PFT] and front abdominal power test [FAPT]), as well as established measures of core stability (isokinetic trunk extension and flexion strength [TES and TFS] and work [TEW and TFW]) over 3 days in 8 young men and women (24.0 +/- 3.1 years). The TES, TFS, TFW, and FAPT were highly reliable, TEW was moderately reliable, and PFT were unreliable for use during a single testing session. Next, we determined if age, weight, and the data from the reliable field test (FAPT) were predictive of TES, TEW, TFS, and TFW in 50 young men and women (19.0 +/- 1.2 years). The FAPT was the only significant predictor of TES and TEW in young women, explaining 16 and 15% of the variance in trunk performance, respectively. Weight was the only significant predictor of TFS and TFW in young women, explaining 28 and 14% of the variance in trunk performance, respectively. In young men, weight was the only significant predictor of TES, TEW, TFS, and TFW, and explained 27, 35, 42, and 33%, respectively, of the variance in trunk performance. In conclusion, the ability of weight and the FAPT to predict TES, TEW, TFS, and TFW was more frequent in young men than women. Additionally, because the FAPT requires few pieces of equipment, is fast to administer, and predicts isokinetic TES and TEW in young women, it can be used to provide a field-based estimate of isokinetic TES and TEW in women without history of back or lower-extremity injury.

Development and reliability of two core stability field tests.

Because of the recognized link between core stability and back and lower extremity injury in sport, additional field tests that assess the strength and power component of core stability are needed to identify athletes at risk of such injury. To that end, we developed and tested the reliability of the front and side abdominal power tests (FAPT and SAPT), which were adapted from plyometric medicine ball exercises. The FAPT and SAPT were performed by explosively contracting the core musculature using the arms as a lever to project a medicine ball. Twenty-four untrained young women (aged 20.9 +/- 1.1 year) completed three trials each of the FAPT and SAPT on separate nonconsecutive days. The average distance the medicine ball was projected on each day was recorded; power was inferred from this measure. There was an approximately 3% increase in the mean distance between the testing sessions for the FAPT and SAPT; this was not significant and indicates there was no learning effect in the measurement protocol. Heteroscedasticity was present in the SAPT data but not the FAPT data. For the FAPT, the intraclass correlation coefficient was 0.95, standard error of measurement was 24 cm, and random error using the limits of agreement method was 67.5 cm. For the SAPT, the intraclass correlation coefficient was 0.93, mean coefficient of variation was 9.8%, and the limits of agreement ratio was 36.8%. The FAPT and SAPT displayed excellent test-retest reliability, as well as acceptable measurement error. These findings suggest the FAPT and SAPT are reliable tests and may be used to assess the power component of core stability in young women.

Kinesthetic motor imagery and spinal excitability: the effect of contraction intensity and spatial localization.

OBJECTIVE: Data on whether motor imagery (MI) modulates spinal excitability are equivocal. The purpose of this study was to determine if imagined muscle contractions of the left plantar flexor (PF) alter spinal excitability, and if so, to determine whether this alteration is intensity dependent and/or localized to the target muscles. Our research questions required two experiments. METHODS: In experiment 1, 16 healthy volunteers performed imagined muscle contractions using a kinesthetic approach with their left PF at 25% and 100% of imagined effort (IE). The soleus H-reflex was evoked during three conditions, which were separated by about 15s: rest (preceding MI), during MI, and recovery (following the cessation of MI). In experiment 2, a subset of subjects from experiment 1 performed MI with their left PF at 100% of IE, while either the soleus or flexor carpi radialis (FCR) H-reflex was measured. RESULTS: In experiment 1, we observed a facilitation of soleus H-wave amplitude during MI compared to the rest and recovery conditions (p<0.05). Furthermore, the soleus H-wave amplitude was greater during 100% than 25% of IE (p<0.05). In experiment 2, soleus and FCR H-wave amplitude increased during imagined muscle contractions of the left PF (p<0.05). These changes were independent of voluntary muscle activity. CONCLUSIONS: These findings suggest MI can increase spinal excitability by the intensity of imagined effort, but this effect is not fully localized to the task specific muscle. SIGNIFICANCE: These data provide evidence that MI can increase spinal excitability in healthy subjects, which suggests future studies are warranted to examine the clinical relevance of this effect. These studies are needed to help establish a therapeutic theory by which to advance motor function rehabilitation using MI.