Randall E. Keyser

Benefits of intensive treadmill exercise training on cardiorespiratory function and quality of life in patients with pulmonary hypertension.

BACKGROUND Pulmonary hypertension (PH) restricts the ability to engage in physical activity and decreases longevity. We examined the impact of aerobic exercise training on function and quality of life in patients with World Health Organization group 1 PH. METHODS Patients were randomized to a 10-week education only (EDU) or education/exercise combined (EXE) group. The exercise program consisted of 24-30 sessions of treadmill walking for 30-45 min per session at 70% to 80% of heart rate reserve. Outcome variables included changes in 6-min walk test (6MWT) distance, time to exercise intolerance, peak work rate (WR) from a cardiopulmonary treadmill test, and quality-of-life measures, including the Short Form Health Survey, version 2 (SF-36v2) and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). RESULTS Data are presented as mean SD. Twenty-three women (age, 54 11 years; BMI, 31 7 kg/m 2 ) were randomized to the EDU (n 5 13) or EXE (n 5 10) groups. Following 10 weeks of intervention, patients in the EXE group demonstrated an improvement in 6MWT distance (56 45 m; P 5 .002), increased time to exercise intolerance (1.9 1.3 min; P 5 .001), and peak WR (26 23 W; P 5 .004). Additionally, the EXE group scored significantly ( P , .050) better on six of the eight scales on SF-36v2, and fi ve of the six scales on CAMPHOR. In contrast, no significant improvement was observed for any of the outcome measures following EDU. No adverse events were noted in either group. CONCLUSION Ten weeks of brisk treadmill walking improved 6MWT distance, cardiorespiratory function, and patient-reported quality of life in female patients with group 1 PH.

The biomechanics of wheelchair propulsion in individuals with and without upper-limb impairment.

We used an instrumented wheelchair ergometer and 3D motion analysis system to collect joint kinematic and temporal data, as well as hand rim and joint kinetics, in 47 manual wheelchair users (MWCUs) (15 with upper-limb impairment and 32 without upper-limb impairment). The group with upper-limb impairment propelled with a higher stroke frequency and reduced hand-rim contact time, and smaller peak joint angles and joint excursion of the wrist, elbow, and shoulder during the contact phase. They also propelled with a reduced power output and reduced hand-rim propulsive and resultant forces, moments, and joint compressive forces. We concluded that these kinematic and kinetic strategies might be a mechanism for allowing MWCUs with upper-limb impairment to remain independent. Additionally, the reduced joint excursion and reduced magnitude of forces may protect them from the development of secondary upper-limb pathologies.

Upper-limb fatigue-related joint power shifts in experienced wheelchair users and nonwheelchair users

This paper evaluates power transfer or shifting across upper-limb segments, resulting from fatigue-inducing wheelchair propulsion. Nineteen manual wheelchair users (WCUs) and ten nonwheelchair users (NUs) participated in this study. Subjects propelled an instrumented wheelchair ergometer at a workload corresponding to 75% of the peak oxygen uptake attained during a maximal-graded exercise tolerance test. Subjects were required to propel the wheelchair for as long as they could at a constant velocity of 3 km/h (32 rpm). The test was terminated when subjects could no longer maintain the target velocity. Peak Performance video-capture system was used to determine upper-limb kinematics. Handrim forces and joint kinematics were used to calculate joint moments and power with the use of an inverse dynamics approach. Results showed that with fatigue, joint power shifts from the shoulder joint to the elbow and wrist joints. Implications for joint injury and propulsion efficiency are discussed.

Exercise intensity: its effect on the high-density lipoprotein profile.

OBJECTIVE To determine the effect of aerobic exercise intensity on the active subfraction of serum high-density lipoprotein (HDL) concentration. DESIGN A randomized control, before-and-after investigation that tested the hypothesis that high-intensity exercise training would result in improvements in serum concentrations of HDL subfraction 2 (HDL2) greater than those accompanying moderate-intensity training. SETTING Exercise tests were completed in a hospital stress testing laboratory, and cholesterol analyses were performed in a university research laboratory. Exercise training was performed in the community at a site determined by the subject. SUBJECTS Subjects were 25 healthy female employees of a teaching hospital. INTERVENTION Maximum treadmill tests and serum cholesterol profiles were assessed in 25 women before and after a 12-week aerobic walking regimen; 12 women in a high-intensity exercise group (HIG) walked at a target heart rate of 80% and 13 women in a moderate-intensity exercise group (MIG) walked at a heart rate of 60% of their heart rate reserve for a distance of 2 miles three times weekly. MAIN OUTCOME MEASURES The main dependent variable was HDL2; other measures of the HDL profile were total HDL and HDL3. Peak oxygen uptake (VO2) was also evaluated as a dependent variable to ensure a general aerobic adaptation resulted from the exercise regimen. Measures were analyzed as pretraining to posttraining change scores and absolute values using independent and dependent t tests as appropriate. Statistical significance was assigned atp < .05. RESULTS Total HDL was 32.3+/-8.5mg/dL before and 40.3+/-10.6mg/dL after training in the MIG and 31.6+/-6.2mg/dL before and 38.2+/-12.0mg/dL after training in the HIG. HDL2 was 14.2+/-5.7mg/dL before and 18.5+/-6.9mg/dL after training in MIG. HDL2 was 13.0+/-6.2mg/dL before and 19.6+/-8.9mg/dL after training in the HIG. Total HDL and HDL2 increased significantly in both groups as a result of exercise training, and intragroup differences were not observed. HDL3 was not affected by exercise training. Training resulted in significant increases in peak VO2 in both MIG and HIG (29.0+/-5.0 to 31.9+/-5.4mL/kg/min in the MIG and 30.7+/-5.2 to 33.5+/-6.3mL/kg/min in the HIG). Intergroup differences in change scores for peak VO2, HDL, and HDL2 were not observed. CONCLUSION The results and analyses did not support the hypothesis that the HIG would acquire increases in HDL2 profile beyond those observed for the MIG. Moderate-intensity training was sufficient to improve the HDL profile, and high-intensity training appeared to be of no further advantage as long as total training volume (total walking distance per week) was constant.

Exercise training and severe caloric restriction: Effect on lean body mass in the obese

The purpose of this study was to investigate the effects of exercise intensity on the body composition of obese subjects during severe caloric restriction. Forty obese subjects (33 women, 7 men; 41 +/- 7.7 years; 106 +/- 26kg; body fat > 25% men, > 30% women) on a commercially prepared OPTIFAST 420kcal/day supplemented fast were randomized into groups that exercised at target heart rates corresponding to 40% and 60% of the heart rate reserve (HRR) at the start of the program. Training volume was similar for both groups at approximately 300kcal per session three times per week for 12 weeks. Body weight, body fat, and lean weight were similar for both exercise intensity groups at week one. Overall, body weight decreased by 15.3 +/- 6.7 kg (p < or = .05), and body fat decreased by 14.9 +/- 5.0 kg (p < or = .05) for the 40 subjects, whereas lean weight remained unchanged. No significant differences in body weight, body fat, or lean weight were observed between the two groups. The results of the current study indicated that while on a supplemented 420-kcal/day fast, exercise at 40% and 60% of the HRR affected body composition similarly when total training volume was held constant at 900kcal/week. Lean weight remained unchanged and accompanied a 14.9 +/- 5.0-kg decrease in body fat, which may have resulted when the volume of exercise (ie, 900kcals/wk) was factored into the exercise prescriptions. These results suggest that exercising at 60% of the HRR offers no advantages for body composition changes over those obtained from exercising at 40% of HRR when the total volume of exercise training is controlled.

Improved Cognitive Performance Following Aerobic Exercise Training in People With Traumatic Brain Injury

OBJECTIVE To examine cognitive function in individuals with traumatic brain injury (TBI) prior to and after participation in an aerobic exercise training program. DESIGN Pre-post intervention study. SETTING Medical research center. PARTICIPANTS Volunteer sample of individuals (N=7) (age, 33.3±7.9y) with chronic nonpenetrating TBI (injury severity: 3=mild, 4=moderate; time since most current injury: 4.0±5.5y) who were ambulatory. INTERVENTION Twelve weeks of supervised vigorous aerobic exercise training performed 3 times a week for 30 minutes on a treadmill. MAIN OUTCOME MEASURES Cognitive function was assessed using the Trail Making Test Part A (TMT-A), Trail Making Test Part B (TMT-B), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Sleep quality and depression were measured with the Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory, version 2 (BDI-II). Indices of cardiorespiratory fitness were used to examine the relation between improvements in cognitive function and cardiorespiratory fitness. RESULTS After training, improvements in cognitive function were observed with greater scores on the TMT-A (10.3±6.8; P=.007), TMT-B (9.6±7.0; P=.011), and RBANS total scale (13.3±9.3; P=.009). No changes were observed in measures of the PSQI and BDI-II. The magnitude of cognitive improvements was also strongly related to the gains in cardiorespiratory fitness. CONCLUSIONS These findings suggest that vigorous aerobic exercise training may improve specific aspects of cognitive function in individuals with TBI and cardiorespiratory fitness gains may be a determinant of these improvements.

A comparison of Qt and a-vO2 in individuals with HIV taking and not taking HAART

PURPOSE The aim of this study was to determine whether highly active antiretroviral therapy (HAART), rather than the direct effect of HIV infection, limits peripheral muscle oxygen extraction-utilization (a-vO(2)) in individuals infected with the human immunodeficiency virus (HIV). METHODS Fifteen subjects (6 female and 9 male) with HIV taking HAART, 15 subjects infected with HIV not taking HAART, and 15 healthy gender and activity level matched non-HIV infected controls (N = 45) performed an maximal treadmill exercise test to exhaustion. Noninvasive cardiac output Qt was measured at each stage and at peak exercise using the indirect Fick method based on the exponential rise carbon dioxide rebreathing method. Intergroup comparisons were adjusted for interactions of peak oxygen consumption ([V02), body surface area, and [V02]t using ANCOVA. RESULTS Peak a-vO(2) was significantly lower (P < 0.05) in subjects with HIV taking HAART (10.0 +/- 0.5 vol%) compared with subjects with HIV not taking HAART (11.7 +/- 0.5 vol%) and noninfected controls (12.7 +/- 0.5 vol%). In subjects with HIV taking HAART, peak heart rate (HR) (170.5 +/- 3.9 bpm) was lower than (P < 0.05) and stroke volume (Vs) (123.0 +/- 3.9 mL x beat-1) at peak exercise was higher (P < 0.05) than subjects with HIV not taking HAART (179.9 +/- 3.5 bpm) (106.6 +/- 3.9 mL x beat-1) and noninfected controls (185.4 +/- 3.8 bpm) (100.6 +/- 4.0 mL.beat-1) upon ANCOVA. There were no significant differences in peak [VO2]t between groups. CONCLUSION Peak a-vO(2) was diminished in subjects infected with HIV taking HAART compared with HIV-infected subjects not taking HAART and noninfected controls matched for age, gender, and physical activity level. Findings of the current study implicated HAART as a primary contributor to decreased muscle oxygen extraction-utilization in individuals infected with HIV.

Decreased peak arteriovenous oxygen difference during treadmill exercise testing in individuals infected with the human immunodeficiency virus

OBJECTIVE To determine if arteriovenous oxygen difference was lower in asymptomatic individuals with human immunodeficiency virus (HIV) infection than in sedentary but otherwise healthy controls. DESIGN Quasi-experimental cross-sectional. SETTING Clinical exercise laboratory. PARTICIPANTS Fifteen subjects (10 men, 5 women) with HIV and 15 healthy gender- and activity level-matched controls (total N=30). INTERVENTION Participants performed an incremental maximal exercise treadmill test to exhaustion. Electrocardiogram, metabolic, and noninvasive cardiac output measurements were evaluated at rest and throughout the tests. Data were analyzed by using analysis of covariance. MAIN OUTCOME MEASURES Peak oxygen consumption (Vo(2)), cardiac output, stroke volume, and arteriovenous oxygen difference. The arteriovenous oxygen difference was determined indirectly using the Fick equation. RESULTS Peak VO(2) was significantly lower (P<.0005) in participants with HIV (24.6+/-1.2mL.kg(-1).min(-1)) compared with controls (32.0+/-1.2mL.kg(-1).min(-1)). There were no significant intergroup differences in cardiac output or stroke volume at peak exercise. Peak arteriovenous oxygen difference was significantly lower (P<.04) in those infected with HIV (10.8+/-0.5 volume %) than in controls (12.4+/-0.5 volume %). CONCLUSION The observed deficit in aerobic capacity in the participants with HIV appeared to be the result of a peripheral tissue oxygen extraction or utilization limitation. In addition to deconditioning, potential mechanisms for this significant attenuation may include HIV infection and inflammation, highly active antiretroviral therapy medication regimens, or a combination of these factors.

Aerobic capacity in late adolescents infected with HIV and controls

Objectives : The objective of this study was to determine if aerobic capacity was diminished in late adolescents infected with HIV compared to controls matched for age, gender, and physical activity level. Study design : This study was a quasi-experimental cross sectional analysis. Subjects (11 female, four male) were 15 late adolescents with HIV (18 - 0.03 years) (CD4: 499.2 - 37.5 cells/mm 3, viral load: 22043 - 9976.6 copies/ml, haematocrit: 36.4 - 1.2) and 15 age, gender, and activity level matched controls (18 - 0.03) who underwent maximal treadmill exercise testing, while oxygen consumption, carbon dioxide production, ventilation, and ECG data were simultaneously recorded via open circuit spirometry and electrocardiography. Results : Peak oxygen consumption ( p < 0.003), peak treadmill stage ( p < 0.003), treadmill duration ( p < 0.004), and oxygen pulse ( p < 0.009) were lower in those infected with HIV compared to controls. Functional aerobic impairment was observed in the late adolescents infected with HIV, pointing toward pathological limitations of the oxidative metabolic pathway. Conclusion : This study has demonstrated that aerobic capacity was reduced substantially in late adolescents infected with HIV, below that observed in controls. The findings suggest that this decrease in oxidative capacity was due to mechanisms other than physiologic deconditioning.

Exercise Capacity and Idebenone Intervention in Children and Adolescents With Friedreich Ataxia

OBJECTIVE To determine the exercise capacity of children and adolescents with Friedreichs Ataxia (FA) and to evaluate the effects of 6 months of idebenone treatment on exercise capacity. DESIGN Exploratory endpoint in a randomized double-blind, placebo-controlled, phase II clinical trial designed to investigate the effects of idebenone on a biomarker of oxidative stress. SETTING Exercise physiology laboratory in a single clinical research center. PARTICIPANTS Ambulatory subjects (N=48; age range, 9-17 y) with genetically confirmed FA. INTERVENTION Idebenone administered orally 3 times a day for a total daily dose of approximately 5, 15, and 45 mg/kg or matching placebo for 6 months. MAIN OUTCOME MEASURES Peak oxygen consumption per unit time (peak VO(2)) and peak work rate (WR) were measured during incremental exercise testing at baseline and after treatment. Echocardiography and neurologic assessments were also completed before and after treatment. RESULTS Baseline mean peak VO(2) +/- SD was 746+/-246 mL/min (16.2+/-5.8 mL/kg/min), and WR was 40+/-23 W for all subjects. Peak VO(2) and WR were correlated with short guanine-adenine-adenine allele length and neurologic function. Relative left ventricular wall thickness was increased but left ventricular ejection fraction was normal in most subjects; there was no relationship between any exercise and echocardiographic measures. There were no significant changes in mean peak VO(2) or WR after idebenone treatment at any dose level relative to placebo. CONCLUSIONS Exercise capacity in children and adolescents with FA was significantly impaired. The basis for the impairment appears to be multifactorial and correlated to the degree of neurologic impairment. Although idebenone has previously been shown potentially to improve features of FA, idebenone treatment did not increase exercise capacity relative to placebo.