Effects of resistance training and aerobic training on ambulation in chronic stroke.

Authors: Kaare Severinsen, MD, PhD Johannes K. Jakobsen, MD, PhD Asger R. Pedersen, PhD Kristian Overgaard, PhD Henning Andersen, MD, PhD

Affiliations:

Stroke

ORIGINAL RESEARCH ARTICLE

From the Hammel Neurorehabilitation and Research Centre, Hammel, Denmark (KS, ARP); Rigshospitalet, Neurocentret, Copenhagen, Denmark (JKJ); Department of Public HealthYSection of Sport Science, Aarhus University (KO); and Department of Neurology, Aarhus University Hospital, Aarhus, Denmark (HA).

Effects of Resistance Training and Aerobic Training on Ambulation in Chronic Stroke

Correspondence: All correspondence and requests for reprints should be addressed to: Kaare Severinsen, MD, PhD, The Research Unit, Hammel Neurorehabilitation and Research Centre, Voldbyvej 15, 8450 Hammel, Denmark.

Disclosures: Supported by grants from the VELUX Foundation and the BEVICA Foundation, both in Denmark. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

0894-9115/14/9301-0029 American Journal of Physical Medicine & Rehabilitation Copyright * 2013 by Lippincott Williams & Wilkins DOI: 10.1097/PHM.0b013e3182a518e1

ABSTRACT Severinsen K, Jakobsen JK, Pedersen AR, Overgaard K, Andersen H: Effects of resistance training and aerobic training on ambulation in chronic stroke. Am J Phys Med Rehabil 2014;93:29Y42.

Objective:

The aim of this study was to directly compare the effects of aerobic training (AT) with progressive resistance training (RT) after stroke to determine whether AT-induced fitness gains or RT-induced strength gains translate into improved ambulation across a 12-wk intervention and whether gains are retained 1 yr after cessation of formal training.

Design: This study is a randomized controlled 12-wk intervention trial with a 1-yr follow-up. Forty-three community-dwelling independent walkers with a chronic ischemic hemiparetic stroke were allocated to AT using a cycle ergometer (n = 13), RT using training machines (n = 14), or low-intensity sham training of the arms (n = 16). The main outcome measures were 6-min walk distance and fast 10-m walking speed.

Results: Comparisons between AT, RT, and sham training revealed no clinically relevant effects on walking velocity or walking distance. Muscle strength improved after RT (P G 0.0001) and was preserved at 1-yr follow-up (P G 0.001). Aerobic capacity increased after AT (P G 0.001) but was lost during the follow-up observation period.

Conclusions: Improvement of muscle strength or aerobic capacity using nonY task-specific training methods does not result in improved ambulation in patients with chronic stroke. Muscle strength gains were maintained at follow-up, whereas all improvements of aerobic capacity were lost, indicating a long-lasting effect of intensive RT even without maintenance training. Key Words:

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Stroke, Rehabilitation, Exercise, Randomized Clinical Trial

Effects of Exercise Training After Stroke Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

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n chronic stroke, ambulation, aerobic capacity, and muscle strength are impaired.1Y3 The aerobic capacity and muscle strength are related to the walking distance and speed, suggesting a potential effect of aerobic training (AT) and resistance training (RT) on ambulation.1,4Y6 A previous controlled clinical trial in stroke showed that AT for 10 wks improves aerobic capacity,7 whereas RT for 1Y3 mos improves muscle strength, as compared with either no intervention8 or sham exercise.9,10 However, in a recent review on physical fitness training for stroke patients,11 overall evidence on whether improvements of aerobic capacity (14 trials) or muscle strength (7 trials) have beneficial effects on ambulation is conflicting, mainly because of heterogeneity in study designs, populations, and outcome measures.11 Of these studies, four applied cycle ergometry7,12Y14; and five, regular progressive RT.8Y10,15,16 A recent case study17 not included in the review reports improvement of walking distance after RT; however, the cases served as their own control group. In a previous study evaluating the effect of body-weightYsupported treadmill training for 3 mos, improvement of walking distance and of aerobic capacity was found.18 However, because treadmill training includes a significant task-specific component of walking, the impact of improved aerobic capacity in isolation remains unclear. AT studies evaluating functional outcomes without task-specific training are sparse and inconclusive.7 In RT studies, improvement on the timed up-and-go test has been reported,8 whereas no effect on walking distance or speed was observed. Other studies have failed to demonstrate improvements of walking capacity,10 or other outcome measures have been used.9 Follow-up studies after RT indicate retention of muscle strength at 5 mos 8 and 4 yrs,19 whereas improvement of exercise capacity, serving as an indirect measure of aerobic capacity, is lost at 3-mo follow-up.12 A single study has directly compared the effect of AT and RT on physical fitness and ambulation using a complex fourgroup design and combined interventions.20 The study reports training-specific improvements of aerobic capacity and muscle strength after AT and RT and increased stair-climbing power, but no followup was performed. In this study, the authors aimed to directly compare the short- and long-term effects of progressive RT and AT on physical fitness and ambulation in chronic hemiparetic stroke. It was hypothesized that (1) improved aerobic capacity induced by AT

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leads to longer walking distance and (2) improved muscle strength induced by RT leads to increased walking velocity. Furthermore, at follow-up, the authors expected muscle strength gains to be preserved and hypothesized that (3) gain in walking velocity was preserved at follow-up. Because no maintenance training was applied, it was hypothesized that (4) improvement of aerobic capacity and gain in walking distance would be lost.

METHODS Design This study is a randomized and controlled population-based study with a 1-yr follow-up including two intervention groups performing RT and AT and a control group performing sham training (ST). The participants performed exercise three times per week for 12 wks using the same training facilities, but members from different groups were not mixed. The participants were not blinded but were informed that they would receive one of three potentially beneficial interventions. Outcome assessments were performed at the study start (baseline), at completion of the training period (after training), and at 1-yr follow-up (follow-up). The examiner evaluating muscle strength and walking distance was blinded to the intervention. Because of limited resources, measurements of walking velocity and aerobic capacity were performed by the physiotherapist, who trained the participants. At follow-up, no blinding was attempted.

Inclusion Criteria The inclusion criteria were as follows: (1) nonhemorrhagic stroke verified by computed tomographic scan; (2) 6Y36 mos have elapsed after stroke; (3) aged 50Y80 yrs; (4) muscle strength of more than 3 on the Medical Research Council scale21 at the paretic lower limb; and (5) walking velocity of less than 1.4 m/sec at a fast 10-m walk test22 (10 mWT), allowing assistive walking devices.

Exclusion Criteria The exclusion criteria were as follows: global aphasia and spatial neglect syndrome, other neurologic disorders including previous stroke, psychiatric disorders, and severe orthopedic or medical morbidity, all evaluated at the initial clinical examination and history taking. Moderate to severe depression was evaluated with the Multiple Depression Inventory,23 with a cutoff value of 25; dementia was evaluated with the MiniYMental State Examination,24 with a cutoff value of 20. However, in stroke

Am. J. Phys. Med. Rehabil. & Vol. 93, No. 1, January 2014

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patients, scores on the MiniYMental State Examination are sometimes low because of stroke sequelae not being caused by dementia, and in these cases, clinical judgment was required. Finally, six or more training sessions missed during this study lead to termination of study participation.

Recruitment The participants were identified from a national database including all hospitalized stroke patients within the catchment area of Aarhus University Hospital during the period of 2004Y2007. Patients in the database who were aged between 50 and 80 yrs at the time of stroke and who had impaired walking at admission received a letter with an invitation to participate in this study (N = 1040). Mail responders (these patients were considered eligible, Fig. 1) had a subsequent telephone interview, and the patients assessed to meet the inclusion criteria underwent a clinical examination including history taking and the Scandinavian Stroke Scale,25 with final assessment of the inclusion and exclusion criteria. Individuals who refused participation (n = 545) were pooled with the nonresponders (n = 328) and

compared with the potential participants (n = 167) on their clinical characteristics as recorded in the database at admission. This revealed that the potential participants (n = 167) were slightly younger (64.5 vs. 66.7 yrs, P G 0.05), were more often men (66% vs. 55%, P G 0.05), and had a poorer walking performance (4 vs. 6 on the Scandinavian Stroke Scale Bwalking[ item, P G 0.05).

Randomization After the baseline evaluations, the patients were allocated into three groups, using block randomization stratified for degree of impaired walking performance at inclusion.

Intervention The participants followed a standardized, but individually adapted, physical training program equally dosed with respect to time (Appendix 1). Each training session consisted of a 5-min warmup period using a lower extremity cycle ergometer (Monark) followed by approximately 1 hr of groupspecific training. All AT sessions were continuously pulse monitored, and every fifth non-AT session was pulse monitored. All training sessions were

FIGURE 1 Flow chart for identification and inclusion of the participants from a population-based cohort of patients with previous stroke. The patients participated in AT, RT, or ST. The four exclusions during intervention in the AT group and the exclusion in the ST group were caused by reduced attendance with six or more missed training sessions, caused by lack of motivation, kidney disease, alcoholism (not recognized at inclusion), epilepsy, and knee pain. www.ajpmr.com


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supervised by the same physiotherapist, and all groups were habituated to the intended training intensity by a gradual increase in training intensity during the first 2Y4 wks (Appendix 1).

Aerobic Training High-intensity AT (n = 13) consisted of 15 mins of strenuous cycle ergometer (Monark) exercise, three times at each session. Training intensity was regularly modified by the physiotherapist, with the aim of reaching a pulse rate of 75% of the heart rate reserve.26 If heart rate measurements were unreliable, as was the case in patients with atrial fibrillation, the Borg Scale was used.

Evaluations

Resistance Training High-intensity progressive RT of both lower limbs (n = 14) consisted of three sets of eight repetitions targeted at an intensity of 80% of onerepetition maximum27 (1RM; i.e., the maximal load that can be lifted once). 1RM was adjusted every second week. In reality, the targeted intensity of 80% of 1RM was too ambitious. The authors had estimated that when participants could lift more than eight repetitions in a specific exercise, this would correspond to approximately 80% of 1RM, but the results of this study show that it was rather approximately 70% of 1RM on average for the different exercises used. Eight-repetition maximum loading corresponds to the recommended loading (8- to 12-repetition maximum) for novice and moderately trained persons training for increased strength according to the American College of Sports Medicine guidelines (this is explained further in Appendix 1). Exercises were performed bilaterally, each limb separately, using RT machines (Nordic Gym). Hip extension and flexion were performed while standing, whereas knee extension, ankle dorsal flexion, ankle plantar flexion, and leg press were performed seated, with knee flexion being performed in a prone position.

Sham Training Low-intensity RT of the arms (n = 16) consisted of three sets of 15 repetitions less than 60% of 1RM bilaterally. The participants performed elbow flexion and extension and shoulder abduction and combined shoulder movements using a pulley.

Posttrial Training There was no scheduled training during the 1-yr follow-up. The patients were verbally encouraged to remain physically active at cessation of training, but individual training programs or instructions were not supplied. The physical activity of the

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participants was self-estimated monthly during follow-up using the Danish version of the Physical Activity Scale (PAS).28 The PAS is a questionnaire estimating 24-hr physical activity ranging from sleep and leisure time to sports. The intensity of each level of activity is expressed as metabolic equivalents, and the physical activity is estimated by multiplying the hours spent performing a specific activity with the corresponding metabolic equivalents for that activity. The PAS is validated in an elderly Danish population but not in a Danish stroke population.

Walking distance was assessed using the 6-min walk test (6MWT), a hand-held stopwatch, and a 30-m lane.29 Walking velocity was evaluated using a 10 mWT (fast) and a flying start.22 The test was repeated three times,22 using a digital photocell timing device (Photocell RLS1nd, Alge-Timing GmbH, Lustenau, Austria). The mean value was used for analysis. Standardized verbal encouragement was applied. Peak aerobic capacity (peak oxygen consumption per unit time [V˙O2]) was assessed using a maximal progressive stepwise cycle ergometer test, a respiratory gas exchange analyzer (AMIS 2001; Innovision, Odense, Denmark), and a heart rate monitor (Polar S810i; Polar Electro Oy, Kempele, Finland), as described in Appendix 1. Maximal isometric knee muscle strength was assessed bilaterally using a dynamometer (BIODEX System 3; Biodex Medical Systems, Inc, New York, United States). The participants were stabilized in the chair using abdominal and thigh straps to eliminate movements of the torso and the hip during knee extension. They became familiar with the test procedure during warm-up by performing five to ten submaximal contractions and one to two maximal contractions before the actual test. Using recorded standardized instructions, the participants were guided to perform three maximal isometric contractions lasting 5 secs each with a 30-sec pause in between at 70 degrees of knee flexion. The coefficient of variation was calculated, and to avoid submaximal performance, test series with more than 10% variation were repeated.1,30 The procedure was always performed first on the nonparetic leg followed by the paretic leg, and the highest peak muscle strength value in the three contractions on each leg was used in all further analyses. Isometric measurements correlate closely with isokinetic measurements30 and were chosen to avoid a possible velocity-dependent effect of spasticity on



antagonist muscle activity.31 Measurement of only knee extensor strength was chosen to reduce test duration and exhaustion because measurements of knee extensor strength are reliable and reproducible and because there is a high intralimb correlation between muscle groups after stroke.32 Impairment was evaluated using the FuglMeyer test,33 spasticity was assessed with the modified Ashworth scale,34 and the Short-FormY36 was used to evaluate health-related self-reported quality-of-life. Physical activity and energy expenditure during follow-up were recorded using the PAS. All used equipments are listed in Appendix 2.

Statistical Analysis The outcome of the block randomization was tested by comparing the three training groups on baseline characteristics (demographic details, 6MWT, 10 mWT, V˙O2 peak, knee muscle strength, FuglMeyer indices, Scandinavian Stroke Scale, modified Ashworth scale, and Short-Form-36) using the nonparametric Kruskal-Wallis test for ordinal and interval variables and the Fisher’s exact test for categorical variables. The outcome measures (6MWT, 10 mWT, and V˙O2 peak) could be analyzed by a linear mixed model with random subject effect and systematic effects of time and training group. Knee muscle strengths could be analyzed jointly for the legs, that is, facilitating comparison of the legs, by extending the linear mixed model with a systematic effect of the legs (paretic vs. nonparetic). Group-specific training and/or follow-up effects were compared by statistical significance testing (significance level, 5%) of the time and group interaction term, and for the knee strengths, the time and group interaction term was compared between the legs to test for different developments in the legs relative to different baseline levels. If the time and group interaction term was found to be statistically significant, group-specific training effects and follow-up effects were compared between the groups by statistical post hoc testing. Post hoc tests were not adjusted for multiple comparisons but compared with the statistically expected number of false significances.

Ethical Approval This study was approved by the local scientific ethics committee. Written informed consent was obtained from all participating patients. The funding sources had no influence on planning, execution, or evaluation of the trial. www.ajpmr.com

RESULTS Five of the 48 included subjects missed six training sessions and were excluded (Fig. 1). One of the dropouts was study related, caused by pain from a former knee replacement (AT group). At follow-up, all 43 subjects completing the 12 wks of training were reevaluated. During follow-up, no cardiac events were reported, whereas one individual in the AT group experienced a minor cerebral stroke during followup without hospital admission. Consequently, no documentation (scanning or clinical description) of the event was performed, and the individual was not excluded. Demographic details and baseline tests are presented in Table 1. Apart from lower body weight in the AT group, there were no statistically significant differences between the three groups, suggesting the randomization to be acceptable. Physical activity during follow-up on the PAS is reported in Appendix 3, and clinical characteristics regarding comorbidities, pharmacologic treatment, and biochemical parameters are reported in Appendix 4; no group differences were observed. ShortFormY36 data were analyzed before and after intervention and at follow-up, without between-group difference (data not shown). Frequency of attendance was similar in the intervention groups (Table 1). Training-intensity adherence to the test protocol, after the initial habituation phase, was less than the intended pulse of 75% of heart rate reserve in the AT group and less than the intended resistance of 80% of 1RM in the RT group.

Ambulation Walking distance did not develop differently over time in the three intervention groups (Fig. 2A). Walking velocity changed differently over time (P G 0.005) in the three training groups (Table 2). In the RT and ST groups, an increase was observed (P G 0.05 and P G 0.005). However, there were no between-group differences, and the increase of 0.09 m/sec and 0.12 m/sec was less than the smallest real difference on a fast 10 mWT of 0.22 m/sec suggested by others.22 During followup, there was a significant decrease in walking velocity in the AT group (P G 0.001), whereas the decrease in the RT and ST groups was nonsignificant (Fig. 2B). Consequently, at follow-up, the walking velocity had decreased in the AT group compared with the RT group (P G 0.01) and the ST group (P G 0.001). Effects of Exercise Training After Stroke


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TABLE 1 Demographic details, baseline characteristics, attendance, and adherence Characteristic No. participants Height, cm Weight, kg Age, yrs Time since stroke, mos 6MWT, m 10 mWT, m/sec V˙O2 peak, ml O2/kg per minute Paretic knee strength, N I m Nonparetic knee strength, N I m Mod-Ashworth (0/1/1+/2) Mod-Ashworth (%) Fugl-Meyer index leg (0Y34) Fugl-Meyer index arm (0Y66) Scandinavian Stroke Scale (0Y58) Sex (male) Paretic side (right) Attendance (% of sessions) Training intensity (% of HRR) Training resistance (% of 1RM) Peak RER Card resp intensity (% of training time spent in pulse interval) G50% HRR 50Y64% HRR 65Y75% HRR 975% HRR

AT Group

RT Group

ST Group

13 169 (159Y180) 68 (49Y119) 69 (50Y80) 14 (11Y29) 313 (79Y505) 0.81 (0.34Y1.33) 18 (9Y27) 92 (51Y144) 106 (56Y184) 4/6/1/2 31/46/8/15

14 173 (153Y183) 88 (49Y138) 68 (57Y78) 19 (8Y36) 287 (65Y551) 0.87 (0.20Y1.37) 16 (10Y27) 101 (8Y176) 124 (77Y205) 11/2/0/1 79/14/0/7 67 (15Y93) 31 (11Y34) 40 (4Y61) 53 (32Y55) 11 (79%) 6 (43%) 94 (86Y100) NA 70 (63Y78) 1.17 (1.03Y1.37)

16 173 (150Y197) 89 (48Y142) 66 (52Y80) 16 (9Y38) 307 (77Y433) 0.89 (0.23Y1.23) 15 (9Y30) 108 (39Y190) 152 (65Y304) 11/2/1/2 69/13/6/13 79 (21Y97) 29 (17Y34) 49 (4Y63) 53 (35Y58) 11 (69%) 11 (69%) 94 (83Y100) NA 59 (50Y72) 1.13 (0.85Y1.27)

28 51 54 9 7 94 66

(13Y33) (5Y63) (41Y58) (69%) (54%) (83Y100) (62Y83) NA 1.10 (0.96Y1.36) 12 26 30 33

(1Y15) (8Y44) (18Y41) (12Y71)

88 (0Y100) 10 (0Y53) 1 (0Y38) 0 (0Y41)

P 0.16 0.05 0.86 0.54 0.97 0.95 0.65 0.72 0.22 0.14 0.58 0.66 0.40 0.50 0.83 0.38

0.39

85 (1Y100) 11 (0Y52) 2 (0Y40) 0 (0Y41)

Demographic details, baseline characteristics, attendance, and adherence to training protocol of the participants. Data are presented as number (percentage distrubution); median (range); and for the modified Ashworth scale, absolute number and percentage of observations in each Ashworth category. Statistical comparisons are performed with the Kruskal-Wallis and Fisher exact tests; and for the Peak RER, analysis of variance. Card resp intensity, cardiac respiratory intensity, measured during exercise; Mod-Ashworth, modified Ashworth scale; HRR, heart rate reserve (HRR = maximal pulse j resting pulse); NA, not applicable; peak RER, peak respiratory exchange ratio.

Aerobic Capacity The peak aerobic capacity developed differently over time (P G 0.005) in the training groups (Fig. 2C, Table 2). It increased in the AT group after 12 wks of aerobic exercise (P G 0.001), and the increase was significantly larger than in the RT (P G 0.05) and sham intervention groups (P G 0.01). At follow-up, the increase in peak aerobic capacity in the AT group was lost. The peak aerobic capacity decreased during follow-up in both the AT and the RT group (P G 0.0001 and P G 0.05, respectively). In the AT group, aerobic capacity was significantly reduced at follow-up relative to the baseline level (P G 0.005).

Muscle Strength The knee extension strength of the nonparetic leg changed differently over time (P G 0.001) in the three intervention groups (Table 2). After 12 wks of RT, strength increased in the RT group only (P G 0.0001; Table 2 and Fig. 3). The increase was

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significantly larger than in the AT group (P G 0.0001) and the ST group (P G 0.001). At follow-up, the increase in knee extension strength at the nonparetic leg was maintained in the RT group compared with baseline (P G 0.0001) and compared with the AT and ST groups (P G 0.001 and P G 0.05, respectively). Furthermore, no significant decrease was observed in the RT group during follow-up (P = 0.21). By using the extended linear mixed model with a systematic effect of the legs, it is shown that the time course of the knee extension strength at the paretic lower limb followed the same pattern as for the nonparetic leg (P = 0.39 test of different pattern), although at a lower general level (on average, 41 N I m lower, P G 0.0001, test for a lower level of strength; Fig. 3). Indeed, analyzed separately, the change in muscle strength in the paretic leg did not differ between the three intervention groups (P = 0.12; Table 2 and Fig. 3). Considering post hoc testing despite this, the paretic knee extension strength increased only in the RT group. The increase was



FIGURE 2 Ambulation and aerobic capacity after intervention and at follow-up. A, Walking distance at the 6MWT; B, walking velocity at the 10 mWT; and C, peak aerobic capacity in the AT group, RT group, and ST group 0, 12, and 64 wks after inclusion. Data are presented as means, and the 95% confidence interval (CI) limits are illustrated.

significant within-group (P G 0.0001) and compared with the AT group (P G 0.05), whereas there was a trend toward difference when compared with the ST group (P = 0.09; Table 2). At follow-up, the increase in the RT group was preserved compared with baseline (P G 0.001) and compared with the AT group (P G 0.05). During follow-up, no significant changes were observed in any of the groups, and the minor graphical trend toward an increase in the ST group (observed in Fig. 3) was non significant (P = 0.44).

nor were there any correlations between changes in the outcome parameters during the follow-up period (data not shown), except in the AT group, in which there was a tendency toward a significant correlation between change in muscle strength on the paretic knee and walking velocity (r = 0.52, P = 0.08). However, this correlation was driven by a considerable decrease in both outcome parameters, as seen in Table 2, which makes interpretation difficult.

DISCUSSION Analysis of Changes By application of Spearman correlations, the association between changes in the various outcome parameters (walking distance vs. peak aerobic capacity and walking velocity vs. muscle strength) after 12 wks of training can be investigated. However, for the AT and the RT group, there was no correlation between change in muscle strength on the paretic leg and walking velocity (r = j0.16, P = 0.6, and r = 0.39, P = 0.16). Likewise, for the AT and RT groups, there was no correlation between changes in peak aerobic capacity and walking distance (r = 0.34, P = 0.25, and r = 0.23, P = 0.42), www.ajpmr.com

In a previous study, relations between muscle strength, aerobic capacity, and ambulation in patients with chronic stroke1 were demonstrated. The correlations were moderate but confirmed the findings of others in various stroke populations4Y6 suggesting that improvement of muscle strength or aerobic capacity might increase walking distance and velocity. The results in the present study show that patients with chronic stroke respond to aerobic and RT protocols by improving aerobic capacity and muscle strength. However, in contrast to the authors’ hypotheses, the improved aerobic capacity Effects of Exercise Training After Stroke


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TABLE 2 Changes in outcome measures Variable

Period

6MWT, m, P = 0.0911 10 mWT, m/sec, P = 0.0037 V˙O2 peak, ml O2/kg per minute, P = 0.0015 Strength-NP, N I m, P = 0.0002 Strength-P, N I m, P = 0.1213

T F T+F T F T+F T F T+F T F T+F T F T+F

AT Group

RT Group

ST Group

19 (j8 to 47) 29.6 (3 to 56) 43.5 (19 to 68) j53 (j81 to j26) j16.9 (j43 to 10) j34.9 (j60 to j10) j34 (j61 to j6) 12.8 (j14 to 39) 8.6 (j16 to 33) 0.05 (j0.04 to 0.13) 0.09 (0.01 to 0.17)a 0.12 (0.04 to 0.19)a j0.19 (j0.28 to j0.11)b j0.06 (j0.14 to 0.02) j0.03 (j0.11 to 0.04) j0.14 (j0.23 to j0.06)d 0.02 (j0.06 to 0.10) 0.08 (0.0 to 0.16)c a 2.5 (1.3 to 3.8) 0.6 (j0.6 to 1.8) 0.06 (j1.1 to 1.2) j4.7 (j6.0 to j3.4)b j1.6 (j2.9 to j0.4)b j1.1 (j2.3 to 0.2) j1.0 (j2.3 to 0.2) j1.0 (j2.2 to 0.2) j2.2 (j3.5 to j0.9)d 1 (j13 to 15) 41 (28 to 55)a 9 (j4 to 21) j1 (j15 to 13) j9 (j22 to 5) 2 (j11 to 14) j0.4 (j14 to 14) 33 (19 to 47)c 10 (j2 to 23) 6 (j8 to 20) 29 (15 to 42)a 12 (j0.6 to 25) j3 (j17 to 11) j2 (j16 to 12) 5 (j7 to 18) 3 (j11 to 17) 27 (13 to 41)c 17 (5 to 30)

Changes in walking distance at the 6MWT, walking velocity at the 10 mWT, peak aerobic capacity (V˙O2 peak), muscle strength at the nonparetic leg (strength-NP), and muscle strength at the paretic leg (strength-P) after 12 wks of training (T), during the 1-yr follow-up (F), and after training and follow-up (T+F). Data are presented as mean (95% confidence interval). P values written in the BVariable[ column indicate the significant difference between the groups in the overall linear mixed model testing for an effect of time and group allocation during the intervention study. a Significant within-group improvement after 12 wks of training (T). b Significant loss during follow-up (F). c Preserved effect at follow-up compared with baseline (T+F). d Significant loss at follow-up compared with baseline (T+F). F indicates changes during the 1-yr follow-up period (follow-up j posttraining); T, changes after training (posttraining j baseline); T+F, changes during the entire study, from baseline to follow-up after 1 yr (follow-up j baseline).

in the AT group does not lead to increased walking distance and the increased muscle strength in the RT group leads only to a minor increase in walking velocity that, despite being statistically significant, is less than the smallest real difference suggested by others.22 The gain in knee extensor muscle strength was preserved as expected, whereas the gain in aerobic capacity was lost at follow-up. Furthermore, no correlations between changes in aerobic capacity and walking distance, as well as between changes in muscle strength and walking velocity, could be demonstrated, illustrating that increased muscle strength

or aerobic capacity did not translate to improvements in ambulation in this cohort of patients with chronic stroke. Although there was an apparently uniform increase in physical activity on the PAS score, none of the interventions proved to be more efficient in increasing the physical activity during the follow-up period or at the 1-yr follow-up evaluation point. After AT, the aerobic capacity in the AT group increased from being very close to the limit required for performing activities of daily living suggested by others (activities of daily living range, 10.5Y17.5 ml O2/kg per minute)2,35 to being well

FIGURE 3 Knee extension muscle strength on the paretic and the nonparetic leg. Knee extension muscle strength at the paretic and the nonparetic leg at baseline, after training, and at follow-up (0, 12, and 64 wks after inclusion, respectively). An almost identical pattern can be observed for the paretic and the nonparetic leg, with significant improvements of muscle strength in the RT group. On the paretic side, an increase in strength is also present in the ST group. CI indicates confidence interval.

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higher than this limit. With no correlation between changes in the aerobic capacity and walking distance, it seems unlikely that further improvements would have lead to other conclusions about impact on walking distance. Training intensity in the RT group was 70% of 1RM and less than the intended intensity of 80% of 1RM, and this could have affected the outcome of this study. As explained in BMETHODS,[ the intended intensity of 80% of 1RM was too ambitious and was based on the assumption that the actual resistance the participants could overcome eight times would correspond to 80% of 1RM; however, the authors’ records showed that it corresponded to 70% of 1RM. Nonetheless, on the basis of the recommendations from the American College of Sports Medicine27 in 2009, the limit of eight repetitions was not changed, and when the participants could perform more than eight repetitions, the resistance was increased (see also Appendix 1). Previous studies suggest that strength on the paretic and the nonparetic leg influences walking speed36; consequently, further strength gains might have increased the gain in walking velocity. However, because of the lack of a convincing transfer effect demonstrated in the present study, it is doubtful whether walking velocity would increase more than the smallest relevant clinical difference despite further strength gain with progressive resistance training being the only intervention. The importance of RT as an add-on intervention remains unclear but requires further research. Previous trials report preserved muscle strength gains at 5 mos and at 4-yr follow-up in chronic stroke,8,19 in accordance with the authors’ observations at follow-up. This is in contrast to healthy elderly losing 62% of muscle strength gain at 1-yr follow-up after 24 wks of RT.37 The results in the present study demonstrate that muscle strength gains in patients with chronic stroke are surprisingly well preserved compared with that in healthy individuals. In contrast, all gain in aerobic capacity was lost at follow-up, which is in accordance with findings in healthy subjects.38 The preservation of muscle strength but not aerobic capacity could be explained by daily day activities being sufficient to maintain muscle strength gains but not aerobic capacity gains. Alternatively, it could be explained by increased muscle strength leading to increased physical activity sufficient to maintain muscle strength gains. However, in the present and other studies,8 daily day activities were insufficiently monitored to demonstrate changes after training, and the PAS data available in the present www.ajpmr.com

study do not show difference between the AT and the RT group. The number of participants in this study is small, and this study might seem underpowered. However, with regard to walking distance (Fig. 2), a slight but uniform increase was observed in all groups after training, with no trends toward difference. With regard to walking velocity, withingroup improvements observed in both the RT and the ST group were considerably less than the smallest real difference of 0.22 m/sec reported by others,22 and there was no trend toward difference between the two groups. Consequently, more participants probably would not lead to another conclusion. The results, however, emphasize the importance of including sham interventions. The study cohort was subject to a possible selection bias during the early recruitment phase because of refusal to participate or no response to the letter with an invitation to participate in this study (Fig. 1). Analyses, based on the initial database information from admission, revealed that compared with patients who refused participation or did not respond at all, the positive responders were younger, had more severe impairment of ambulation at admission, and were more frequently men. This could reflect that some of the oldest patients identified in the database refused participation because of the strain of study participation and that some patients, only moderately affected at admission, overcame their stroke symptoms. The design of the present study allowed comparisons between AT and RT, and to simplify the interpretation, the authors deliberately chose interventions without task-specific components. In one previous study, without follow-up, a direct comparison of regular PRT and AT using cycle ergometry has been performed,20 demonstrating improved muscle strength after PRT and increased aerobic capacity after AT, whereas ambulation did not improve, in accordance with this study’s findings. As in the present study, their results indicate a very limited transfer effect without task-specific components in the intervention. Application of taskspecific interventions including predominantly RT39 and AT18 is possible; however, direct comparison of the contribution of RT and AT would be difficult. Despite the lack of convincing transfer effect in the present study, the results of this study emphasize the potential effect of RT and AT serving as add-on to task-specific intervention; however, this clearly needs to be studied further. Effects of Exercise Training After Stroke


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REFERENCES

Study Limitations Despite standardized verbal instructions and standardized procedures during evaluations, unblinded postintervention measurements of walking velocity and aerobic capacity as well as unblinded measurements at follow-up remain to be limitations of this study. The lack of task specificity was intentional and is not considered a limitation. Measurement of only knee extensor muscle strength might also be a limitation because potential dynamic changes between agonists and antagonists after PRT8 could not be evaluated. Application of the PAS score, not being validated in stroke patients, could be a limitation. Some individuals found the test difficult to use, and some reported unrealistic high physical activity, probably because of subclinical cognitive impairments. Exclusion of noncompleters from the analysis limits the generalizability of the findings, and the number of participants could also have been a limitation of this study because some of the results might have been interpreted differently with more participants. The correlation between changes in knee muscle strength and walking velocity in the RT group, especially, could have ended up being significant with more participants. This could have affected the analysis of transfer effect of muscle strength gain on ambulation. There is, however, no reason to believe that the increase in walking velocity or the strength of the correlation would have changed with more participants.

CONCLUSIONS Improvement of aerobic capacity using a cycle ergometer does not lead to increased walking distance in chronic stroke, and improvements of aerobic capacity are lost at 1-yr follow-up in the absence of maintenance training. Increased muscle strength using RT machines leads to a statistically significant increase in walking velocity, which is, however, less than the level of clinical relevance. Muscle strength gain was preserved at follow-up without maintenance training. Interpretation of the importance of muscle strength changes is difficult, but it remains of interest because sufficient strength is required for overground walking. The results emphasize that muscle strength gains are surprisingly long lasting even without maintenance training, but the results also indicate that RT should probably be combined with taskspecific elements of gait training to achieve clinical impact on walking velocity.

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1. Severinsen K, Jakobsen JK, Overgaard K, et al: Normalized muscle strength, aerobic capacity, and walking performance in chronic stroke: A population-based study on the potential for endurance and resistance training. Arch Phys Med Rehabil 2011;92:1663Y8 2. Ivey FM, Macko RF, Ryan AS, et al: Cardiovascular health and fitness after stroke. Top Stroke Rehabil 2005;12:1Y16 3. Andrews AW, Bohannon RW: Distribution of muscle strength impairments following stroke. Clin Rehabil 2000;14:79Y87 4. Patterson SL, Forrester LW, Rodgers MM, et al: Determinants of walking function after stroke: Differences by deficit severity. Arch Phys Med Rehabil 2007;88:115Y9 5. Bohannon RW, Andrews AW: Correlation of knee extensor muscle torque and spasticity with gait speed in patients with stroke. Arch Phys Med Rehabil 1990; 71:330Y3 6. Hsu AL, Tang PF, Jan MH: Analysis of impairments influencing gait velocity and asymmetry of hemiplegic patients after mild to moderate stroke. Arch Phys Med Rehabil 2003;84:1185Y93 7. Potempa K, Lopez M, Braun LT, et al: Physiological outcomes of aerobic exercise training in hemiparetic stroke patients. Stroke 1995;26:101Y5 8. Flansbjer UB, Miller M, Downham D, et al: Progressive resistance training after stroke: Effects on muscle strength, muscle tone, gait performance and perceived participation. J Rehabil Med 2008;40:42Y8 9. Ouellette MM, LeBrasseur NK, Bean JF, et al: Highintensity resistance training improves muscle strength, self-reported function, and disability in long-term stroke survivors. Stroke 2004;35:1404Y9 10. Kim CM, Eng JJ, MacIntyre DL, et al: Effects of isokinetic strength training on walking in persons with stroke: A double-blind controlled pilot study. J Stroke Cerebrovasc Dis 2001;10:265Y73 11. Brazzelli M, Saunders DH, Greig CA, et al: Physical fitness training for stroke patients. Cochrane Database Syst Rev 2011;CD003316 12. Bateman A, Culpan FJ, Pickering AD, et al: The effect of aerobic training on rehabilitation outcomes after recent severe brain injury: A randomized controlled evaluation. Arch Phys Med Rehabil 2001; 82:174Y82 13. Katz-Leurer M, Carmeli E, Shochina M: The effect of early aerobic training on independence six months post stroke. Clin Rehabil 2003;17:735Y41 14. Lennon O, Carey A, Gaffney N, et al: A pilot randomized controlled trial to evaluate the benefit of the cardiac rehabilitation paradigm for the non-acute ischaemic stroke population. Clin Rehabil 2008;22: 125Y33 15. Inaba M, Edberg E, Montgomery J, et al: Effectiveness of functional training, active exercise, and resistive



exercise for patients with hemiplegia. Phys Ther 1973;53:28Y35

prescribing exercise. Med Sci Sports Exerc 2011;43: 1334Y59

16. Sims J, Galea M, Taylor N, et al: Regenerate: Assessing the feasibility of a strength-training program to enhance the physical and mental health of chronic post stroke patients with depression. Int J Geriatr Psychiatry 2009;24:76Y83

27. American College of Sports Medicine: American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc 2009;41:687Y708

17. Hill TR, Gjellesvik TI, Moen PM, et al: Maximal strength training enhances strength and functional performance in chronic stroke survivors. Am J Phys Med Rehabil 2012;91:393Y400 18. Macko RF, Ivey FM, Forrester LW, et al: Treadmill exercise rehabilitation improves ambulatory function and cardiovascular fitness in patients with chronic stroke: A randomized, controlled trial. Stroke 2005; 36:2206Y11 19. Flansbjer UB, Lexell J, Brogardh C: Long-term benefits of progressive resistance training in chronic stroke: A 4-year follow-up. J Rehabil Med 2012;44:218Y21 20. Lee MJ, Kilbreath SL, Singh MF, et al: Comparison of effect of aerobic cycle training and progressive resistance training on walking ability after stroke: A randomized sham exercise-controlled study. J Am Geriatr Soc 2008;56:976Y85 21. Compston A: Aids to the investigation of peripheral nerve injuries. Medical Research Council: Nerve Injuries Research Committee. His Majesty’s Stationery Office: 1942; pp. 48 (iii) and 74 figures and 7 diagrams; with aids to the examination of the peripheral nervous system. By Michael O’Brien for the Guarantors of Brain. Saunders Elsevier: 2010; pp. [8] 64 and 94 Figures. Brain 2010;133:2838Y44 22. Flansbjer UB, Holmback AM, Downham D, et al: Reliability of gait performance tests in men and women with hemiparesis after stroke. J Rehabil Med 2005;37:75Y82 23. Bech P, Rasmussen NA, Olsen LR, et al: The sensitivity and specificity of the Major Depression Inventory, using the Present State Examination as the index of diagnostic validity. J Affect Disord 2001;66: 159Y64 24. Folstein MF, Folstein SE, McHugh PR: BMini-mental state[. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189Y98 25. Scandinavian Stroke Study Group: Multicenter trial of hemodilution in ischemic strokeVBackground and study protocol. Stroke 1985;16:885Y90 26. Garber CE, Blissmer B, Deschenes MR, et al: American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: Guidance for

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28. Aadahl M, Jorgensen T: Validation of a new selfreport instrument for measuring physical activity. Med Sci Sports Exerc 2003;35:1196Y202 29. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories: Guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111Y7 30. Harbo T, Brincks J, Andersen H: Maximal isokinetic and isometric muscle strength of major muscle groups related to age, body mass, height, and sex in 178 healthy subjects. Eur J Appl Physiol 2012;112: 267Y75 31. Knutsson E, Martensson A, Gransberg L: Influences of muscle stretch reflexes on voluntary, velocitycontrolled movements in spastic paraparesis. Brain 1997;120(pt 9):1621Y33 32. Bohannon RW, Andrews AW: Relationships between impairments in strength of limb muscle actions following stroke. Percept Mot Skills 1998;87(pt 2): 1327Y30 33. Fugl-Meyer AR, Jaasko L, Leyman I, et al: The poststroke hemiplegic patient. 1. A method for evaluation of physical performance. Scand J Rehabil Med 1975; 7:13Y31 34. Bohannon RW, Smith MB: Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 1987;67:206Y7 35. Ainsworth BE, Haskell WL, Whitt MC, et al: Compendium of physical activities: An update of activity codes and MET intensities. Med Sci Sports Exerc 2000;32(suppl):S498Y504 36. Bohannon RW, Walsh S: Nature, reliability, and predictive value of muscle performance measures in patients with hemiparesis following stroke. Arch Phys Med Rehabil 1992;73:721Y5 37. Fatouros IG, Kambas A, Katrabasas I, et al: Strength training and detraining effects on muscular strength, anaerobic power, and mobility of inactive older men are intensity dependent. Br J Sports Med 2005;39: 776Y80 38. Toraman NF: Short term and long term detraining: Is there any difference between young-old and old people? Br J Sports Med 2005;39:561Y4 39. Yang YR, Wang RY, Lin KH, et al: Task-oriented progressive resistance strength training improves muscle strength and functional performance in individuals with stroke. Clin Rehabil 2006;20:860Y70


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Appendix 1: Training Algorithm

Progressive RT (RT group)

Progression of Training Intensity in the Intervention Groups Maximal isometric knee muscle strength was assessed bilaterally using a dynamometer (BIODEX System 3; Biodex Medical Systems, Inc) at 70 degrees of knee flexion. A standardized test protocol including recorded verbal encouragement and three isometric repetitions lasting 5 secs each1 was applied. Peak aerobic capacity was assessed using a maximal progressive cycle ergometer test performed as a stepwise test, the load being increased by 10Y30 W every 90 secs. The initial load and progression rate were chosen individually with the aim of reaching exhaustion within 5Y10 mins. Furthermore, a respiratory gas exchange analyzer and a heart rate monitor were used.

AT Group Week 0 1

Training Session No. 1 2 3

2

4 5 6

3

7 8 9

4Y12 13 52

10Y36

Test and Training Baseline evaluation 50% HRR2 (Borg3 12Y13), 1Y2 intervals of 8Y10 mins 55% HRR (Borg 12Y13), 1Y2 intervals of 10 mins 55% HRR (Borg 12Y13), 2Y3 intervals of 8Y10 mins 60% HRR (Borg 13Y14), 2Y3 intervals of 8Y10 mins 60% HRR (Borg 13Y14), 2Y3 intervals of 10Y12 mins 65% HRR (Borg 14Y16), 2Y3 intervals of 10Y12 mins 65% HRR (Borg 14Y16), 2Y3 intervals of 12 mins 70% HRR (Borg 14Y16), 2Y3 intervals of 12 mins 70% HRR (Borg 14Y16), 3 intervals of 12 mins 75% HRR (Borg 14-16), 3 intervals of 12 mins Evaluation, after 12 wks of training 1-yr follow-up evaluation

Percentage of HRR = (heart rate during exercise j resting heart rate)/(maximal heart rate j resting heart rate) 100. HRR indicates heart rate reserve.

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Week 0 1 2 3 4 5Y12 13

Training Session No. 1 2 3 4 5 6 7 8 9 10 11 12 13Y36

52

Test and Training Baseline evaluation 50% 1RM,4 2 8 repetitions 55% 1RM, 2 8 repetitions 55% 1RM, 2 8 repetitions 60% 1RM, 2 8 repetitions 60% 1RM, 3 8 repetitions 65% 1RM, 3 8 repetitions 65% 1RM, 3 8 repetitions 70% 1RM, 3 8 repetitions 70% 1RM, 3 8 repetitions 75% 1RM, 3 8 repetitions 75% 1RM, 3 8 repetitions 80% 1RM, 3 8 repetitions 80% 1RM, 3 8 repetitions Evaluation, after 12 wks of training 1-yr follow-up evaluation

Maximal muscle strength (1RM) was tested every second week throughout the intervention period in all exercises except dorsal flexion. Heart rate monitoring was performed three times during the training period in weeks 1, 7, and 12. Actually, the targeted intensity of 80% of 1RM was an overestimation. The way the RT intensity was controlled in the RT group was in practice by progressing to an increased load when the patients could lift more than eight repetitions in a specific exercise. It was estimated that this would correspond to approximately 80% of 1RM, but the authors’ records of training intensity show that it was rather approximately 70% on average for the different exercises used (similarly, those in the ST group were not allowed to progress in load until they could perform 15 repetitions). Eight-repetition maximum loading corresponds to the recommended loading (8- to 12-repetition maximum) for novice and moderately trained persons training for increased strength according to the American College of Sports Medicine guidelines (American College of Sports Medicine,5 2009).

Low-intensity RT (ST group) Week 0 1 2 3Y12 13 52

Training Session No. 1 2 3 4 5 6 7Y36

Test and Training Baseline evaluation 50% 1RM, 2 10 repetitions 50% 1RM, 3 12 repetitions 50% 1RM, 3 12 repetitions 55% 1RM, 3 12 repetitions 55% 1RM, 3 15 repetitions 55% 1RM, 3 15 repetitions 60% 1RM, 3 15 repetitions Evaluation, after 12 wks of training 1-yr follow-up evaluation

Maximal muscle strength (1RM) was tested every second week throughout the intervention period for the pull-down and rowing exercise. All other exercises were tested every fourth week. Heart rate monitoring was performed three times during the training period in weeks 1, 7, and 12.



Appendix References: 1. Harbo T, Brincks J, Andersen H: Maximal isokinetic and isometric muscle strength of major muscle groups related to age, body mass, height, and sex in 178 healthy subjects [published online ahead of print May 3, 2011]. Eur J Appl Physiol 2011 2. Karvonen MJ, Kentala E, Mustala O: The effects of training on heart rate; a longitudinal study. Ann Med Exp Biol Fenn 1957;35:307Y15 3. Borg G: Perceived exertion as an indicator of somatic stress. Scand J Rehabil Med 1970;2:92Y8 4. Fleck SJ, Kraemer WJ: Basic principles of resistance training and exercise prescription. Designing resistance training programmes, ed 3. Champaign, IL, Human Kinetics, 2004, pp 3Y12 5. American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc 2009; 41:687Y708

f. Heart rate monitor, Polar S810i, Polar Electro Oy, Professorinitie 5, 90440 Kempele, Finland. E-mail: [email protected] Appendix 3: Legend Physical Activity Scale at Baseline, After Training, and at 1-Yr Follow-up Physical Activity Scale scores expressed as metabolic equivalents at the start and the end of the trial and monthly during the 1-yr follow-up study for all patients (upper panel) and for each of the groups (lower panel). The physical activity in the combined group of all three interventions (upper panel) increased by 5 metabolic equivalents (j6 to 19; median [range]) at the study end (P G 0.05) and remained increased at the end of the follow-up period after 1 yr by 2 (j14 to 21); P = 0.045. In all three groups, the physical activity increased at the study end without differences between the groups (lower panel). *P G 0.05. AU indicates arbitrary units.

Appendix 2: Suppliers List a. Cycle ergometer: Monark, http://www.monarkexercise. se/. E-mail: [email protected] b. Resistance training machines: Nordic Gym, http://www.nordicgym.com/. E-mail: info@ nordicgym.com c. Digital timing devices: Photocell RLS1nd, AlgeTiming GmbH, Lustenau, Austria. E-mail: [email protected] d. Isometric dynamometer: BIODEX System 3 dynamometer, Biodex Medical Systems, Inc, New York, United States. E-mail: [email protected] e. Online respiratory gas exchange analyzer: AMIS 2001. Innovision, Linnedvej 75, Odense, 5260 Denmark. E-mail: [email protected]

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Appendix 4 Clinical Characteristics, Comorbidity, and Pharmacology No. Patients Antithrombotic treatment Aspirin Dipyridamole Clopidogrel Warfarin Antihypertensive treatment Beta blockers Calcium antagonists Diuretics Angiotensin II inhibitors ACE inhibitors Cholesterol-lowering treatment Statins Antidepressive treatment SSRI Diabetes Insulin treatment Oral anti-diabetics Cardiac state Previous cardiac stroke Previous PTCA Angina pectoris Intermittent claudication Biochemistry, mmol/l Total cholesterol LDL cholesterol HDL cholesterol HbA1c

27 19 5 5 6 2 5 7 11 21 20 2 10 4 6 0 0

4.0 (2.4Y6.8) 1.9 (0.7Y4.9) 1.3 (0.7Y3.9) 0.059 (0.051Y0.085)

Clinical characteristics of the participants regarding comorbidities and pharmacologic treatment as well as selected biochemical parameters. ACE indicates angiotensin-converting enzyme; HbA1c, glycosylated hemoglobin; HDL, high-density lipoprotein; LDL, low-density lipoprotein; PTCA, percutaneous transluminal coronary angioplasty; SSRI, selective serotonin reuptake inhibitor.

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Effects of aerobic training, resistance training, or combined resistance-aerobic training on the left ventricular myocardium in a rat model.

Effects of weight-shift training on walking ability, ambulation, and weight distribution in individuals with chronic stroke: a pilot study.

Effect of combined aerobic and resistance training versus aerobic training on arterial stiffness.

About the article: Effect of combined aerobic and resistance training versus aerobic training on arterial stiffness.

Effects of aerobic training, resistance training, or both on cardiorespiratory and musculoskeletal fitness in adolescents with obesity: the HEARTY trial.

Effect of aerobic training and aerobic and resistance training on the inflammatory status of hypertensive older adults.

Resistance and Aerobic Training Sequence Effects on Energy Consumption in Females.

Effects of combined training vs aerobic training on cognitive functions in COPD: a randomized controlled trial.

Chronic Effects of Resistance Training in Breast Cancer Survivors.

The Effects of High Intensity Interval Training vs Steady State Training on Aerobic and Anaerobic Capacity.

Effects of nonlinear resistance and aerobic interval training on cytokines and insulin resistance in sedentary men who are obese.

Effects of aerobic training, resistance training, or both on percentage body fat and cardiometabolic risk markers in obese adolescents: the healthy eating aerobic and resistance training in youth randomized clinical trial.

Effects of Resistance Training on Obese Adolescents.

Resistance training as a preconditioning strategy for enhancing aerobic exercise training outcomes in COPD.

Delineating the effects of aerobic training versus aerobic capacity on satellite cell behaviour in humans.

The Chronic Effects of Low- and High-Intensity Resistance Training on Muscular Fitness in Adolescents.

Influence of Aerobic Training and Combinations of Interventions on Cognition and Neuroplasticity after Stroke.

Effects of community-based virtual reality treadmill training on balance ability in patients with chronic stroke.

How much will older adults exercise? A feasibility study of aerobic training combined with resistance training.

Effects of high intensity training and continuous endurance training on aerobic capacity and body composition in recreationally active runners.

Effects of phase proprioceptive training on balance in patients with chronic stroke.

Whole-body aerobic resistance training circuit improves aerobic fitness and muscle strength in sedentary young females.

Effect of aerobic exercise training on regional blood flow and vascular resistance in diabetic rats.

Aerobic training prevents dexamethasone-induced peripheral insulin resistance.