Evaluating the use of intra-articular injections as a treatment for painful hip osteoarthritis: a randomized, double-blind, multicenter, parallel-group study comparing a single 6-mL injection of hylan G-F 20 with saline.

OBJECTIVE: Hip osteoarthritis (OA) is difficult to treat. Steroid injections reduce pain with short duration. With widespread adoption of office-based, image-guided injections, hyaluronic acid is a potentially relevant therapy. In the largest clinical trial to-date, we compared safety/efficacy of a single, 6-mL image-guided injection of hylan G-F 20 to saline in painful hip OA. METHOD: 357 patients were enrolled in a multicenter, double-blind, randomized saline placebo- controlled trial. Subjects were ≥35 years of age, with painful (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]-A1:5.0-8.0; numeric rating scale [NRS]: 0-10) mild-to-moderate hip OA (Kellgren-Lawrence grade II/III) and minimal contralateral hip pain (WOMAC-A1 < 4). Outcome measures included "pain on walking" (WOMAC-A1 and -A), Patient Global Self-Assessment (PTGA), WOMAC-A1 responder rate (+≥2 points on NRS), and adverse events (AEs) over 26 weeks. RESULTS: 357 patients (hylan G-F 20 single:182; saline:175) were enrolled. Both groups demonstrated significant pain improvement from baseline over 26 weeks (P < 0.0001); saline-induced pain reduction was a remarkable 35%. WOMAC-A and PTGA scores also significantly improved (P < 0.0001). No statistically significant difference was observed between groups in WOMAC-A1 scores (hylan G-F 20 single:-2.19 ± 0.16; saline:-2.26 ± 0.17) or WOMAC-A1 responders (41-52%). Treatment-related AE rates at target hip were similar (hylan G-F 20 single:23 patients [12.8%]; saline:12 [7.0%]). Posthoc analysis found, despite protocol requirements, many patients had psychological (31%) or potential neuropathic pain (27.5%) conditions. CONCLUSION: A single 6-mL hylan G-F 20 injection or saline for painful hip OA resulted in similar, statistically significant/clinically relevant pain and function improvements up to 6 months following injection; no differences between hylan G-F 20 and saline placebo were observed.

The HealtheSteps™ lifestyle prescription program to improve physical activity and modifiable risk factors for chronic disease: a pragmatic randomized controlled trial.

BACKGROUND: Our objective was to determine the influence of the HealtheSteps™ lifestyle prescription program on physical activity and modifiable risk factors for chronic disease in individuals at risk. METHODS: One hundred eighteen participants were recruited from 5 sites in Southwestern Ontario, Canada and randomized to either the intervention (HealtheSteps™ program, n = 59) or a wait-list control group (n = 59). The study comprised three phases: an Active Phase (0 to 6 months) consisted of bi-monthly in-person lifestyle coaching with access to a suite of eHealth technology supports (Heathesteps app, telephone coaching and a private HealtheSteps™ social network) followed by a Minimally-Supported Phase I (6 to 12 months), in which in-person coaching was removed, but participants still had access to the full suite of eHealth technology supports. In the final stage, Minimally-Supported Phase II (12 to 18 months), access to the eHealth technology supports was restricted to the HealtheSteps™ app. Assessments were conducted at baseline, 6, 12 and 18 months. The study primary outcome was the 6-month change in average number of steps per day. Secondary outcomes included: self-reported physical activity and sedentary time; self-reported eating habits; weight and body composition measures; blood pressure and health-related quality of life. Data from all participants were analyzed using an intent-to-treat approach. We applied mixed effects models for repeated measurements and adjusted for age, sex, and site in the statistical analyses. RESULTS: Participants in HealtheSteps™ increased step counts (between-group [95% confidence interval]: 3132 [1969 to 4294], p < 0.001), decreased their sitting time (- 0.08 [- 0.16 to - 0.006], p = 0.03), and improved their overall healthful eating (- 1.5 [- 2.42 to - 0.58], p = 0.002) to a greater extent compared to control at 6 months. Furthermore, exploratory results showed that these individuals maintained these outcomes 12 months later, after a minimally-supported phase; and retained improvements in sedentary time and improved healthful eating after 18 months. No differences in self-reported physical activity, health-related quality of life, weight, waist circumference or blood pressure were observed between groups at 6 months. CONCLUSIONS: Our findings suggest that HealtheSteps™ is effective at increasing physical activity (i.e., step counts per day), decreasing weekday sitting time, and improving healthful eating in adults at increased risk for chronic disease after 6 months; however, we did not see change in other risk factors. Nonetheless, the maintenance of these behaviours with minimal support after 12 and even 18 months indicates the promise of HealtheSteps™ for long-term sustainability. TRIAL REGISTRATION: The trial was registered on April 6, 2015 with ClinicalTrials.gov (identifier: NCT02413385 ).

Scoping review report: obesity in older adults.

Obesity is associated with an increased risk for early death, heart disease and stroke, disability and several other comorbidities. Although there is concern about the potential burden on health-care services with the aging demographic and the increasing trend of obesity prevalence in older adults, evidence on which to base management strategies is conflicting for various reasons. The analytic framework for this review is based on a scoping review methodology, and was conducted to examine what is known about the diagnosis, treatment and management of obesity in older adults. A total of 492 relevant research articles were identified using PubMed, Scirus, EBSCO, Clinicaltrials.gov, Cochrane Reviews and Google Scholar. The findings of this review indicate that the current WHO (World Health Organization)-recommended body mass index, waist circumference and waist-to-hip ratio obesity thresholds for the general adult population may not be appropriate for older adults. Alternatively, weight change or physical fitness may be more useful measures of mortality and health risk in obese older adults. Furthermore, although obesity in older adults is associated with several disorders that increase functional disability, epidemiological evidence suggests that obesity is protective against mortality in seniors. Consequently, the trend toward increasing prevalence of obesity in older adults will lead to an increase in unhealthy life years and health-care costs. The findings from this review also suggest that treatment strategies for obese older adults should focus on maintaining body weight and improving physical fitness and function rather than weight loss, and that a combination of aerobic and resistance exercise appears to be the most effective strategy. In conclusion, this review demonstrates the need for more research to clarify the definition of obesity in older adults, to establish criteria for evaluating when to treat older adults for obesity, and to develop effective treatment strategies focused on functional outcomes in obese older adults.

CHARMM: the biomolecular simulation program.

CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems, the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983.

It Is the Time to Think About a Treat-to-Target Strategy for Knee Osteoarthritis.

Osteoarthritis (OA) is a rheumatic disease that affects the well-being of the patient, compromises physical and mental function, and affects other quality of life aspects. In the literature, several evidence-based guidelines and recommendations for the management of knee osteoarthritis (KOA) are available. These recommendations list the different therapeutic options rather than addressing a hierarchy between the treatments and defining the real target. Therefore, a question arises: are patients and physicians satisfied with the current management of KOA? Actually, the answer may be negative, thus suggesting a change in our therapeutic strategies. In this article, we address this challenge by suggesting that it is time to develop a "treat to target strategy" for KOA.

The energetics of off-rotamer protein side-chain conformations.

Non-rotameric ("off-rotamer") conformations are commonly observed for the side-chains of protein crystal structures. This study examines whether such conformations are real or artifactual by comparing the energetics of on and off-rotamer side-chain conformations calculated with the CHARMM energy function. Energy-based predictions of side-chain orientation are carried out by rigid-geometry mapping in the presence of the fixed protein environment for 1709 non-polar side-chains in 24 proteins for which high-resolution (2.0 A or better) structures are available. For on-rotamer conformations, 97.6 % are correctly predicted; i.e. they correspond to the absolute minima of their local side-chain energy maps (generally to within 10 degrees or less). By contrast, for the observed off-rotamer side-chain conformations, 63.8 % are predicted correctly. This difference is statistically significant (P<0.001) and suggests that while most of the observed off-rotamer conformations are real, many of the erroneously predicted ones are likely to be artifacts of the X-ray refinements. Probabilities for off-rotamer conformations of the non-polar side-chains are calculated to be 5.0-6.1 % by adaptive umbrella-sampled molecular dynamics trajectories of individual amino acid residues in vacuum and in the presence of an average protein or aqueous dielectric environment. These results correspond closely to the 5.7 % off-rotamer fraction predicted by the rigid-geometry mapping studies. Since these values are about one-half of the 10.2 % off-rotamer fraction observed in the X-ray structures, they support the conclusion that many of the latter are artifacts. In both the rigid-geometry mapping and the molecular dynamics studies, the discrepancies between the predicted and observed fractions of off-rotamer conformations are largest for leucine residues (approximately 6 % versus 16.6 %). The simulations for the isolated amino acid residues indicate that the real off-rotamer frequency of 5-6 % is consistent with the internal side-chain and local side-chain-backbone energetics and does not originate from shifts due to the protein. The present results suggest that energy-based rotation maps can be used to find side-chain positional artifacts that appear in crystal structures based on refinements in the 2 A resolution range.

The discrepancy between recommendations and clinical practice for viscosupplementation in osteoarthritis: mind the gap!

Recently AAOS, ACR and OARSI revised their recommendations for the management of knee osteoarthritis (OA) and for hand, knee and hip joints. During ISIAT (International Symposium on Intra-Articular Treatments) 2013 round table on recommendations about the use of intra-articular Hyaluronic Acid (IAHA) in OA, several considerations were elaborated by the ISIAT Technical Expert Panel (TEP) regarding discrepancy between recommendations and clinical practice. The ISIAT TEP gathered the following eight suggestions regarding the drawing of recommendations on the use of IAHA in OA and its comparison with other treatments. It is necessary to merge data coming from both RCTs and registers. Only studies with a strong level of evidence should be taken into account. A common threshold of efficacy should be assessed for comparing treatments. Evaluation of hard outcomes is essential. The effect size of placebo as comparator should be attentively considered in RCTs. Particular attention should be given to different phenotypes of OA that may possibly respond differently to each treatment. Compliance and long-term side effects of different therapeutic approaches should be evaluated. Pharmacoeconomic evaluation should be performed on the long term.

Multiple dysfunctions in developmental and activational stages of T lymphocytes, B lymphocytes and monocytes in ARC and AIDS patients.

Peripheral blood leukocytes from ARC and AIDS patients were examined before and after phytohemagglutinin (PHA) stimulation by dual color flow cytometry and monoclonal antibodies which identify developmental and activational stages of T lymphocytes, B cells and monocytes. There was a persistent elevation in the total number of circulating Ia+ lymphocytes with progressive selection for B1+ Ia+ lymphocytes and T suppressor cells and a concurrent reduction in the antigen-presenting monocytes. Following PHA stimulation there was a marked decrease in all subsets of Ia+ lymphocytes and monocytes. These results indicate (a) multicellular dysfunctions in the immunosurveillance mechanisms in AIDS, and (b) that many functional subsets of circulating lymphocytes and monocytes were already activated and therefore poorly responsive to additional antigenic or mitogenic stimuli.

A self-paced step test to predict aerobic fitness in older adults in the primary care clinic.

OBJECTIVES: To study the potential usefulness of a submaximal self-paced step test as a prediction of maximal aerobic capacity (VO2max) in older adults in the primary care setting. DESIGN: Data were collected during a prospective randomized study of an exercise program. SETTING: Four university family medical clinics in London, Ontario, Canada. PARTICIPANTS: A random sample of 240 healthy older (> or =65) men (n = 118) and women (n = 122) from four family medical clinics underwent self-paced step testing in the clinic with a family physician (n = 16), and step testing and a maximal exercise treadmill test with measurement of respired gases in an exercise laboratory. Testing was done in random order (clinic/laboratory) separated by 2 weeks and then repeated at 52 weeks, following introduction of an exercise program. Relationships between outcome variables were examined by Pearson correlation coefficients while prediction of VO2max was examined using multivariate regression analysis. Cross-validation with 30 age-matched hypertensive and 40 age-matched post-hip arthroplasty patients was used to test the accuracy of the predictive models. MEASUREMENTS: Measured VO2max, predicted VO2max, step test time, step test heart rate, body mass index (BMI), and O2 pulse. RESULTS: Two hundred women (n = 108) and men (n = 92) completed both the initial and 52-week assessments. Stepping time, heart rate, age, BMI, and O2 pulse were strongly associated with VO2max for both a normal and a fast step pace and were chosen to develop the predictive model. Normal step-pace correlation with VO2max (ml/kg/min) was no different (female 0.93: male 0.91) from fast pace (0.95:0.90) with no difference between clinic and laboratory measurement at baseline or 52 weeks. Cross-validation showed no significant difference from the main group using the predictive model. CONCLUSIONS: The self-paced step test is a safe and simple clinical instrument that strongly and reliably predicts VO2max, is sensitive to change, and is generalizable in the family practice setting among community-dwelling older adults differing in fitness and health status.

Determination of prefracture physical function in community-dwelling people who fracture their hip.

BACKGROUND: Prefracture physical function must be accurately determined to set appropriate and attainable goals for rehabilitation following hip fracture. This is especially important for people who were living independently prior to their fracture. This study determines reliability and internal consistency of a prefracture physical function questionnaire (PFPFQ) completed by both patients and knowledgeable informants (KIs). METHODS: A 20-item PFPFQ, including ambulation, transfers, balance, and self-care domains, was developed using focus groups. Community-dwelling patients with a hip fracture (N = 40, 77.9 +/- 8 years) completed the PFPFQ on two occasions during postoperative acute care. Forty KIs were identified by the patients and also completed the PFPFQ on two occasions via telephone interview. Day-to-day reliability of the patients and KIs [intraclass correlation coefficients (ICC)], and internal consistency [Kuder-Richardson coefficient (KR)] of the PFPFQ were determined. RESULTS: Intrarater reliability was high with ICCs (95% confidence interval) of 0.94 (0.89, 0.96) for patients and 0.96 (0.93, 0.98) for KIs. Interrater reliability on occasion 1 had an ICC of 0.81 (0.69, 0.88). Internal consistency of the patient responses on the first occasion was high (KR coefficient = 0.896). CONCLUSIONS: The PFPFQ is a reliable and internally consistent instrument for determining prefracture physical function in community-dwelling people who fracture their hip. In situations where patients with a hip fracture are unable to provide this necessary information, KIs can provide reliable estimates of prefracture function to assist in setting appropriate rehabilitation goals.

Estimation of arterial PCO2 in the elderly.

Arterial PCO2 (PaCO2), determined directly in the radial artery, was compared with indirect estimates of PCO2 in six elderly men (mean age 73.8 yr). Estimates of PaCO2 included arterialized venous PCO2 (PavCO2); end-tidal PCO2; mean alveolar PCO2, calculated by using a reconstruction of the alveolar oscillation in PCO2 and accounting for the presence of dead space (time-weighted mean for PCO2 throughout the respiratory cycle); and values calculated by using the empirical formula developed by Jones et al. (N. L. Jones, D. G. Robertson, and J. W. Kane. J. Appl. Physiol. 47: 954-960, 1979), which incorporates end-tidal PCO2 and tidal volume (PaCO2 derived from end-tidal PCO2 and VT). Measurements were made at rest and during cycle ergometry at 25 and 50 W while the subjects breathed various gas mixtures (euoxic-eucapnic, hypoxic-eucapnic, hyperoxic-eucapnic, and hyperoxic-hypercapnic). The mean differences between the estimates and the actual PaCO2 at rest and in 25- and 50-W exercise were as follows: PavCO2, 0.3 +/- 0.7 (SD), -0.1 +/- 0.7, and 1.8 +/- 1.2 Torr; end-tidal PCO2, 2.9 +/- 1.7, 4.0 +/- 3.1, and 3.7 +/- 3.2 Torr; time-weighted mean of alveolar PCO2, 2.6 +/- 1.9, 3.3 +/- 3.1, and 3.6 +/- 3.8 Torr; and PaCO2 derived from end-tidal PCO2 and VT, 2.4 +/- 1.3, 1.3 +/- 3.0, and 0.6 +/- 2.9 Torr. It is concluded that mean PavCO2 agreed most closely with mean PaCO2 both at rest and in exercise. All methods of deriving PaCO2 using measurements from the respired gases overestimated arterial values at rest. Of the noninvasive techniques, mean estimates calculated using the regression equation developed by Jones et al. corresponded most closely with PaCO2 in exercise.

Cardiovascular responses to facial cooling are age and fitness dependent.

PURPOSE: Aging of the cardiovascular system may be altered by differences in physical fitness. We investigated the cardiovascular responses to brief periods of facial cooling (5 degrees C) in 20 healthy men differing in age and aerobic fitness (VO2max). METHODS: Facial cooling was administered at rest in the supine position during 60-s quiet breathing to 6 fit young (FY; VO2max = 75.8 +/- 18 mL x kg(-1) x min(-1); 29 +/- 7 yr), 6 sedentary young (SY; VO2max = 36.0 +/- 2.2 mL x kg(-1) x min(-1); 27 +/- 3 yr), 6 fit old (FO; VO2max = 56.1 +/- 4.0 mL x kg(-1) x min(-1); 54 +/- 5 yr), and 6 sedentary old (SO; VO2max = 29.6 +/- 5.0 mL x kg(-1) x min(-1); 62 +/- 2 yr) volunteers. The following were measured before and after facial cooling: heart rate (HR), mean arterial blood pressure (MAP), pressure-rate product (PRP), and M-mode echocardiographically determined left ventricular internal dimensions, peak circumferential shortening (peak V(CF)), and ejection fraction (EF). RESULTS: Facial cooling produced a statistically significant bradycardia in all groups except for the SO whereas MAP was increased in the young groups but unchanged in the older groups. Pressure-rate product was significantly reduced in the FY, unchanged in the SY and FO, and significantly increased in the SO group. None of the groups showed a change in left ventricular dimensions, whereas only the SO group showed an increase in peak V(CF) (P < 0.05). CONCLUSIONS: These data suggest that endurance training and fitness level do not significantly alter cardiovascular responses to facial cooling in young men or physically fit older men. However, in older subjects, a sedentary lifestyle appears to be associated with an absent facial cooling reflex bradycardia, an increased PRP, and contractility (peak V(CF)).

Verapamil improves left ventricular filling and exercise performance in hypertensive and normotensive elderly individuals.

OBJECTIVE: To study the effect of verapamil slow release (SR) upon left ventricular diastolic function and exercise capacity in newly diagnosed older hypertensive subjects compared with normotensive elderly and young controls. DESIGN: Cross-sectional prospective trial. INTERVENTIONS: Doppler echocardiography at rest and graded maximal exercise testing (with breath-by-breath gas analysis) before and 4 h after administration of oral verapamil SR 240 mg, and before and after 12 weeks of daily medication. MAIN RESULTS: Verapamil administration normalized resting blood pressure in the older hypertensive group, but did not alter blood pressure in older normotensive or young groups. Resting heart rate was not altered in any of the groups. Both the older hypertensive and normotensive groups showed improvement in measures of diastolic filling after verapamil ingestion. Specifically, the older hypertensive group showed significantly faster isovolumic relaxation time (IVRT). In the older normotensive group IVRT was not changed, but the E:A ratio (the ratio of early to late peak transmitral flow velocity) was increased after verapamil. No differences were observed between the effects of verapamil after acute ingestion (4 h) or with chronic use (12 weeks) in any of the variables measured. In the younger group diastolic filling was not altered after verapamil ingestion. In both the elderly normotensive and hypertensive groups maximum oxygen consumption was significantly improved following verapamil ingestion. Again, no differences were observed between 4 h and 12 weeks. In the younger subjects exercise performance was not changed after verapamil ingestion. CONCLUSIONS: Verapamil SR improved left ventricular diastolic function and exercise performance in hypertensive and normotensive elderly individuals. Verapamil normalized blood pressure in the hypertensive subjects, but did not alter blood pressure in the normotensive elderly or younger subjects.

Exercise for older patients with chronic disease.

Coronary artery disease, hypertension, congestive heart failure, type 2 diabetes mellitus, osteoarthritis, osteoporosis, and cognitive disorders become more prevalent as people age. Besides delaying the onset of many of these conditions, regular exercise may improve function and delay disability and morbidity in those who have them. Further, exercise may work synergistically with medication to combat the effects of some chronic diseases. Special adaptations for older patients include lower-intensity exercise (eg, fewer repetitions), low-impact exercise (cycling, exercise while sitting), and modified equipment (smaller weights, special shoes, loose clothing). Unresolved issues include development of optimal strategies for motivating older patients to begin and maintain exercise programs.

Exercises for patients with knee osteoarthritis.

Rest is an important part of the treatment for osteoarthritis, but it must be balanced by regular exercise. Exercise is essential for two reasons: It keeps your joints from becoming stiffer, and it strengthens the muscles surrounding the joints. Strong muscles provide needed support, making movement easier and reducing pain.

In-line skating injuries: patterns and protective equipment use.

The incidence of in-line skating injuries has increased with the rapid growth in the sport's popularity, but few studies have examined patterns of injuries.

Central versus peripheral cardiovascular risk in metabolic syndrome.

Individuals with metabolic syndrome (MetS; i.e., three of five of the following risk factors (RFs): elevated blood pressure, waist circumference, triglycerides, blood glucose, or reduced HDL) are thought to be prone to serious cardiovascular disease and there is debate as to whether the disease begins in the peripheral vasculature or centrally. This study investigates hemodynamics, cardiac function/morphology, and mechanical properties of the central (heart, carotid artery) or peripheral [total peripheral resistance (TPR), forearm vascular bed] vasculature in individuals without (1-2 RFs: n = 28), or with (≥3 RFs: n = 46) MetS. After adjustments for statin and blood pressure medication use, those with MetS had lower mitral valve E/A ratios (<3 RFs: 1.24 ± 0.07; ≥3 RFs: 1.01 ± 0.04; P = 0.025), and higher TPR index (<3 RFs: 48 ± 2 mmHg/L/min/m(2); ≥3 RFs: 53 ± 2 mmHg/L/min/m(2); P = 0.04). There were no differences in heart size, carotid artery measurements, cardiovagal baroreflex, pulse-wave velocity, stroke volume index, or cardiac output index due to MetS after adjustments for statin and blood pressure medication use. The use of statins was associated with increased inertia in the brachial vascular bed, increased HbA1c and decreased LDL cholesterol. The independent use of anti-hypertensive medication was associated with decreased predicted [Formula: see text] triglycerides, diastolic blood pressure, interventricular septum thickness, calculated left ventricle mass, left ventricle posterior wall thickness, and left ventricle pre-ejection period, but increased carotid stiffness, HDL cholesterol, and heart rate. These data imply that both a central cardiac effect and a peripheral effect of vascular resistance are expressed in MetS. These data also indicate that variance in between-group responses due to pharmacological treatments are important factors to consider in studying cardiovascular changes in these individuals.

Non-alpha-adrenergic effects on systemic vascular conductance during lower-body negative pressure, static exercise and muscle metaboreflex activation.

AIM: This study tested the hypothesis that non-α-adrenergic mechanisms contribute to systemic vascular conductance (SVC) in a reflex-specific manner during the sympathoexcitatory manoeuvres. METHODS: Twelve healthy subjects underwent lower-body negative pressure (LBNP, -40 mmHg) as well as static handgrip exercise (HG, 20% of maximal force) followed by post-exercise forearm circulatory occlusion (PECO, 5 min each) with and without α-adrenergic blockade induced by phentolamine (PHE). Aortic blood flow, finger blood pressure and superficial femoral artery blood flow were measured to calculate cardiac output, SVC and leg vascular conductance (LVC) during the last minute of each intervention. RESULTS: Mean arterial pressure (MAP) decreased more during LBNP with PHE compared with saline (-7 ± 7 vs. -2 ± 5%, P = 0.016). PHE did not alter the MAP response to HG (+20 ± 12 and +24 ± 16%, respectively, for PHE and saline) but decreased the change in MAP during PECO (+12 ± 7 vs. +21 ± 14%, P = 0.005). The decrease in SVC and LVC with LBNP did not differ between saline and PHE trials (-13 ± 10 vs. -17 ± 10%, respectively, for SVC, P = 0.379). In contrast, the SVC response to HG increased from -9 ± 12 with saline to + 5 ± 15% with PHE (P = 0.002) and from -16 ± 15 with saline to +1 ± 16% with PHE during PECO (P = 0.003). LVC responses to HG or PECO were not different from saline with PHE. CONCLUSIONS: Non-α-adrenergic vasoconstriction was present during LBNP. The systemic vasoconstriction during static exercise and isolated muscle metaboreflex activation, in the absence of leg vasoconstriction, was explained by an α-adrenergic mechanism. Therefore, non-α-adrenergic vasoconstriction is more emphasized during baroreflex, but not metaboreflex-mediated sympathetic activation.