Effects of remote limb ischemic conditioning on muscle strength in healthy young adults: A randomized controlled trial.

Remote limb ischemic conditioning (RLIC) is a clinically feasible method in which brief, sub-lethal bouts of ischemia protects remote organs or tissues from subsequent ischemic injury. A single session of RLIC can improve exercise performance and increase muscle activation. The purpose of this study, therefore, was to assess the effects of a brief, two-week protocol of repeated RLIC combined with strength training on strength gain and neural adaptation in healthy young adults. Participants age 18-40 years were randomized to receive either RLIC plus strength training (n = 15) or sham conditioning plus strength training (n = 15). Participants received RLIC or sham conditioning over 8 visits using a blood pressure cuff on the dominant arm with 5 cycles of 5 minutes each alternating inflation and deflation. Visits 3-8 paired conditioning with wrist extensors strength training on the non-dominant (non-conditioned) arm using standard guidelines. Changes in one repetition maximum (1 RM) and electromyography (EMG) amplitude were compared between groups. Both groups were trained at a similar workload. While both groups gained strength over time (P = 0.001), the RLIC group had greater strength gains (9.38 ± 1.01 lbs) than the sham group (6.3 ± 1.08 lbs, P = 0.035). There was not a significant group x time interaction in EMG amplitude (P = 0.231). The RLIC group had larger percent changes in 1 RM (43.8% vs. 26.1%, P = 0.003) and EMG amplitudes (31.0% vs. 8.6%, P = 0.023) compared to sham conditioning. RLIC holds promise for enhancing muscle strength in healthy young and older adults, as well as clinical populations that could benefit from strength training.

Dose of remote limb ischemic conditioning for enhancing learning in healthy young adults.

Remote limb ischemic conditioning (RLIC) is a technique in which tissues distant from the target organ are exposed to brief, sub-lethal bouts of ischemia. The effects of remotely applied ischemic conditioning are systemically transferred to the target organ, and typically manifested as protection from subsequent ischemic injury. Previous studies in our lab have found and confirmed that RLIC enhances learning and retention during motor training on a balance task. The current study tested the effect of RLIC dose (number of cycles) on learning enhancement in young, healthy adults. Forty healthy participants age 18-40 years were randomized to receive 5 cycles of sham conditioning (n = 9), 3 cycles of RLIC (n = 11), 4 cycles of RLIC (n = 10), or 5 cycles of RLIC (n = 10) using a blood pressure cuff around the upper arm once a day for 7 consecutive weekdays (Days 1-7). Participants concurrently trained on a balance task, bimanual cup stacking task, and a discrete sequence production task on Days 3-7. Change in performance on each of the three tasks was compared across groups. Participants in all four groups improved their performance on each of the three tasks over time. However, RLIC at any dose did not enhance learning on any of the three tasks. While RLIC is safe, inexpensive, and clinically feasible, reproducibility may be challenged by unidentified factors, raising critical challenges to the straightforward translation of RLIC for improving rehabilitation outcomes in individuals recovering from neurological injury.

Remote Limb Ischemic Conditioning and Motor Learning: Evaluation of Factors Influencing Response in Older Adults.

Remote limb ischemic conditioning (RLIC) is a clinically feasible method of promoting tissue protection against subsequent ischemic insult. Recent findings from our lab demonstrated that RLIC robustly enhances motor learning in young, healthy humans. The next step is to determine which individuals would receive maximum benefit from RLIC before applying these findings to clinical rehabilitation populations such as stroke. Numerous factors, such as age, sex, body mass index (BMI), and cardiovascular comorbidities may influence the response. Sixty-nine participants aged 40-80 were randomized to receive either RLIC (n = 33) or sham (n = 36) conditioning. Participants underwent seven consecutive sessions consisting of RLIC or sham conditioning with a blood pressure cuff on the upper extremity and motor training on a stability platform balance task, with two follow-up sessions. Balance change (post-test-pre-test) was compared across participants, groups, and the factors of age, sex, BMI, and comorbidities. Participants in both groups improved their performance on the balance task from pre- to post-test. Overall balance change was independently associated with age and BMI. There was no difference in balance change between RLIC and Sham groups. However, RLIC significantly enhanced balance performance in participants with no comorbidities. Compared with our previous study in young adults, middle-aged and older adults demonstrated smaller improvements on the balance task. RLIC enhanced learning in middle-aged and older adults only in the absence of pre-defined comorbidities. RLIC may be a promising tool for enhancing motor recovery, but the accumulation of comorbidity with age may decrease its effectiveness.

Recumbent Stepper Submaximal Test response is reliable in adults with and without stroke.

PURPOSE: The purpose of the present study was to determine the reliability of the exercise response (predicted peak VO2) using the total body recumbent stepper (TBRS) submaximal exercise test in: 1) healthy adults 20-70 years of age and 2) adults participating in inpatient stroke rehabilitation. We hypothesized that the predicted peak VO2 (Visit 1) would have an excellent relationship (r > 0.80) to predicted peak VO2 (Visit 2). We also wanted to test whether the exercise response at Visit 1 and Visit 2 would be significantly different. METHODS: Healthy adults were recruited from the Kansas City metro area. Stroke participants were recruited during their inpatient rehabilitation stay. Eligible participants completed 2 TBRS submaximal exercise tests between 24 hours and 5 days at similar times of day. RESULTS: A total of 70 participants completed the study. Healthy adults (n = 50) were 36 M, 38.1 ± 10.1 years and stroke participants (n = 20) were 15 M, 62.5 ± 11.8 years of age. The exercise response was reliable for healthy adults (r = 0.980, p<0.01) and stroke participants (r = 0.987, p<0.01) between Visit 1 and Visit 2. Repeated Measures ANOVA showed a significant difference in predicted values between the two visits for healthy adults (47.2 ± 8.4 vs 47.7 ± 8.5 mL∙kg-1∙min-1; p = 0.04) but not for stroke participants (25.0 ± 9.9 vs 25.3 ± 11.4 mL∙kg-1∙min-1; p = 0.65). CONCLUSION: These results suggest that the exercise response is reliable using the TBRS submaximal exercise test in this cohort of healthy adults and stroke participants.

Estimated Prestroke Peak VO2 Is Related to Circulating IGF-1 Levels During Acute Stroke.

Background Insulin-like growth factor-1 (IGF-1) is neuroprotective after stroke and is regulated by insulin-like binding protein-3 (IGFBP-3). In healthy individuals, exercise and improved aerobic fitness (peak oxygen uptake; peak VO2) increases IGF-1 in circulation. Understanding the relationship between estimated prestroke aerobic fitness and IGF-1 and IGFBP-3 after stroke may provide insight into the benefits of exercise and aerobic fitness on stroke recovery. Objective The purpose of this study was to determine the relationship of IGF-1 and IGFBP-3 to estimated prestroke peak VO2 in individuals with acute stroke. We hypothesized that (1) estimated prestroke peak VO2 would be related to IGF-1 and IGFBP-3 and (2) individuals with higher than median IGF-1 levels will have higher estimated prestroke peak VO2 compared to those with lower than median levels. Methods Fifteen individuals with acute stroke had blood sampled within 72 hours of hospital admission. Prestroke peak VO2 was estimated using a nonexercise prediction equation. IGF-1 and IGFBP-3 levels were quantified using enzyme-linked immunoassay. Results Estimated prestroke peak VO2 was significantly related to circulating IGF-1 levels (r = .60; P = .02) but not IGFBP-3. Individuals with higher than median IGF-1 (117.9 ng/mL) had significantly better estimated aerobic fitness (32.4 ± 6.9 mL kg-1 min-1) than those with lower than median IGF-1 (20.7 ± 7.8 mL kg-1 min-1; P = .03). Conclusions Improving aerobic fitness prior to stroke may be beneficial by increasing baseline IGF-1 levels. These results set the groundwork for future clinical trials to determine whether high IGF-1 and aerobic fitness are beneficial to stroke recovery by providing neuroprotection and improving function.

The relationship of pro-inflammatory markers to vascular endothelial function after acute stroke.

Purpose/Aim: Data from chronic stroke studies have reported reduced blood flow and vascular endothelial function in the stroke-affected limb. It is unclear whether these differences are present early after stroke. First, we investigated whether vascular endothelial function in the stroke-affected limb would be different from healthy adults. Second, we examined whether between-limb differences in vascular endothelial function existed in the stroke-affected arm compared to the non-affected arm. Last, we tested whether reduced vascular endothelial function was related to pro-inflammatory markers that are present early after stroke. MATERIALS AND METHODS: Vascular endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery within 72 h post-stroke. All participants withheld medications from midnight until after the procedure. Ultrasound scans and blood draws for pro-inflammatory markers occurred on the same day between 7:30 am and 9:00 am. RESULTS: People with acute stroke had significantly lower FMD (4.2% ± 4.6%) than control participants (8.5% ± 5.2%, p = 0.037). Stroke participants had between-limb differences in FMD (4.2% ± 4.6% stroke-affected vs. 5.3% ± 4.4% non-affected, p = 0.02), whereas, the control participants did not. Of the pro-inflammatory markers, only vascular cell adhesion molecule-1(VCAM-1) had a significant relationship to FMD (stroke-affected limb, r = -0.62, p = 0.03; non-affected limb, r = -0.75, p = 0.005), but not tumor necrosis factor alpha nor interleukin-6. CONCLUSIONS: Vascular endothelial function is reduced starting in the early stage of stroke recovery. People with higher levels of VCAM-1 had a lower FMD response.

Use of a Nonexercise Estimate for Prestroke Peak Vo2 During the Acute Stroke Hospital Stay.

PURPOSE: For individuals with acute stroke, it is difficult to conduct an exercise test to assess peak oxygen consumption (peak Vo2). Therefore, the purpose of this study was to use a clinically feasible tool for assessing prestroke peak Vo2 using a nonexercise estimation equation to test whether estimated prestroke peak Vo2 was related to the functional outcome measures at discharge from the hospital in individuals after an acute stroke. We hypothesized that the estimated prestroke peak Vo2 would be significantly related to discharge Physical Performance Test (PPT), 6-minute walk test (6MWT), and lower extremity Fugl-Meyer (LEFM) assessment. METHODS: Estimated prestroke peak Vo2 was calculated using a previously validated prediction equation using the following variables: body mass index, age, sex, resting heart rate, and a self-reported measure of physical activity. Outcome measures were assessed 4 days after enrollment or immediately before discharge (whichever occurred first). RESULTS: Thirty-four participants (mean age = 56.0, SD = 12.6 years; 20 men) with acute stroke were enrolled within 48 hours of admission. For all individuals, mean estimated prestroke peak Vo2 was 27.3 (SD = 7.4) mL·kg-1·min-1 and had a weak, nonsignificant relationship with the PPT (r = 0.19; P = .28), 6MWT (r = 0.10; P = .56), and LEFM (r = 0.32; P = .06). However, when considering sex, women, but not men, had a significant relationship with LEFM (r = 0.73; P = .005) and moderate but nonsignificant relationship with PPT (r = 0.53; P = .06) and 6MWT (r = 0.47; P = .10). CONCLUSIONS: Within 48 hours of stroke admission, we were able to administer a nonexercise equation to estimate prestroke peak Vo2. For the entire sample, functional measures conducted at discharge were not related to estimated prestroke peak Vo2. However, when considering sex, the relationship between prestroke Vo2 and the functional measures was strengthened.

Decrease in Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-1 Ratio in the First Week of Stroke Is Related to Positive Outcomes.

BACKGROUND: High insulin-like growth factor-1 (IGF-1), measured once during acute stroke, is associated with greater survival rates and lower stroke severity. However, information is lacking regarding how IGF-1 availability, determined by IGF-1's ratio to insulin-like growth factor binding protein-3 (IGFBP-3), relates to recovery and how the response of IGF-1 during the first week of stroke relates to outcomes. The purpose of this study was to determine the following: (1) the relationship between percent change in IGF-1 and IGF-1 ratio during the first week of stroke and stroke outcomes; and (2) the difference in percent change in IGF-1 and IGF-1 ratio in individuals being discharged home and individuals being discharged to inpatient facilities. METHODS: IGF-1 and IGFBP-3 were quantified from blood sampled twice (<72 hours of admission; 1 week post stroke) in 15 individuals with acute stroke. Length of stay, modified Rankin Scale at 1 month, and discharge destination were obtained from electronic medical records. RESULTS: Percent change in IGF-1 ratio was related to length of stay (r = .54; P = .04). Modified Rankin Scale (n = 10) was related to percent change in IGF-1 (r = .90; P < .001) and IGF-1 ratio (r = .75 P = .01). Individuals who went home (n = 7) had decreases in IGF-1 (-24 + 25%) and IGF-1 ratio (-36 + 50%), whereas individuals who went to inpatient facilities (n = 8) had increases in IGF-1 (37 + 46%) and IGF-1 ratio (30 + 40%). These differences were significant (IGF-1: P = .008; IGF-1 ratio: P = .01). CONCLUSION: Our findings suggest that a decrease in IGF-1 and IGF-1 ratio during the first week of stroke is associated with favorable outcomes: shorter length of stay, greater independence at 1 month on the modified Rankin Scale, and discharging home.

Decreased tidal volume may limit cardiopulmonary performance during exercise in subacute stroke.

PURPOSE: The aim of this retrospective study was to determine whether pulmonary function was reduced at submaximal and peak exercise in subacute stroke (SG) when compared with sedentary adults (CON). METHODS: Ten individuals with subacute stroke and 10 sedentary, age- and gender-matched adults performed cardiopulmonary exercise testing (CPET), using a recumbent stepper. We used independent t tests to determine between-group differences at peak effort. We used repeated-measures analysis of variance with Test Minute (minutes 1-6) as the within-subject factor and Group (SG, CON) as the between-subject factor to assess cardiopulmonary submaximal performance. RESULTS: The SG had significantly lower values (P < .05) for oxygen uptake, minute ventilation ((Equation is included in full-text article.)E), and tidal volume (VT) than CON at peak effort of the CPET. During CPET submaximal effort, we report a significant main effect for Test Minute and Group for VT and respiratory rate but no main effect of Group for (Equation is included in full-text article.)E. To maintain adequate (Equation is included in full-text article.)E during submaximal effort and decreased VT, higher respiratory rate was observed. CONCLUSIONS: These results suggest that diminished VT in subacute stroke patients may limit performance during submaximal and peak effort of CPET. Rehabilitation professionals should consider methods for improving pulmonary function during stroke rehabilitation.

Use of Accelerometers to Examine Sedentary Time on an Acute Stroke Unit.

BACKGROUND AND PURPOSE: Observational studies demonstrate low levels of physical activity during inpatient stroke rehabilitation. There are no prior studies that have objectively measured sedentary time on the acute stroke unit and whether sedentary time is related to functional outcomes. The purpose of this study was to characterize sedentary time after acute stroke and determine whether there is a relationship to functional performance at discharge. METHODS: Thirty-two individuals (18 men; 56.5 ± 12.7 years) with acute stroke were enrolled within 48 hours of hospital admission. An accelerometer was placed on the stroke-affected ankle to measure 24-hour activity and was worn for 4 days or until discharge from the hospital. Performance of activities of daily living, walking endurance, and functional mobility were assessed using the Physical Performance Test, Six-Minute Walk Test, and Timed Up and Go, respectively. RESULTS: Mean percent time spent sedentary was 93.9 ± 4.1% and percent time in light activity was 5.1 ± 2.4%. When controlling for baseline performance, the mean time spent sedentary per day was significantly related to Physical Performance Test performance at discharge (r = -0.37; P = .05), but not the Six-Minute Walk Test or Timed Up and Go. DISCUSSION AND CONCLUSIONS: Patients with acute stroke were sedentary most of their hospital stay. To minimize the potential negative effects of inactivity, our data suggest that there should be greater emphasis on increasing physical activity during the hospital stay.Video Abstract Available for more insights from the authors (Supplemental Digital Content 1, http://links.lww.com/JNPT/A101).

Cardiopulmonary exercise testing is well tolerated in people with Alzheimer-related cognitive impairment.

OBJECTIVE: To retrospectively assess whether cardiopulmonary exercise testing would be well tolerated in individuals with Alzheimer disease (AD) compared with a nondemented peer group. DESIGN: We retrospectively reviewed 575 cardiopulmonary exercise tests (CPETs) in individuals with and without cognitive impairment caused by AD. SETTING: University medical center. PARTICIPANTS: Exercise tests (N=575) were reviewed for nondemented individuals (n=340) and those with AD-related cognitive impairment (n=235). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The main outcome measure for this study was reporting the reason for CPET termination. The hypothesis reported was formulated after data collection. RESULTS: We found that in cognitively impaired individuals, CPETs were terminated because of fall risk more often, but that overall test termination was infrequent-5.5% versus 2.1% (P=.04) in peers without cognitive impairment. We recorded 6 cardiovascular and 7 fall risk events in those with AD, compared with 7 cardiovascular and 0 fall risk events in those without cognitive impairment. CONCLUSIONS: Our findings support using CPETs to assess peak oxygen consumption in older adults with cognitive impairment caused by AD.

Cross-validation of the recumbent stepper submaximal exercise test to predict peak oxygen uptake in older adults.

BACKGROUND: Submaximal exercise testing can have a greater application in clinical settings because peak exercise testing is generally not available. In previous work, a prediction equation was developed to estimate peak oxygen consumption (Vo2) using a total body recumbent stepper (TBRS) and the Young Men's Christian Association (YMCA) protocol in adults who were healthy. OBJECTIVE: The purpose of the present study was to cross-validate the TBRS peak Vo2 prediction equation in older adults. DESIGN: A cross-sectional study was conducted. METHODS: Thirty participants (22 female, 8 male; mean age=66.8 years, SD=5.52; mean weight=68.51 kg, SD=13.39) who previously completed a peak exercise test and met the inclusion criteria were invited to participate in the cross-validation study. Within 5 days of the peak Vo2 test, participants completed the TBRS submaximal exercise test. The TBRS submaximal exercise test equation was used to estimate peak Vo2. The variables in the equation included age, weight, sex, watts (at the end of the submaximal exercise test), and heart rate (at the end of the submaximal exercise test). RESULTS: A strong correlation was found between the predicted peak Vo2 and the measured peak Vo2. The difference between the values was 0.9 mL·kg(-1)·min(-1), which was not statistically different. The standard error of the estimate was 4.2 mL·kg(-1)·min(-1). LIMITATIONS: The sample included individuals who volunteered to perform a peak exercise test, which may have biased the results toward those willing to exercise to fatigue. CONCLUSION: The data suggest the TBRS submaximal exercise test and prediction equation can be used to predict peak Vo2 in older adults. This finding is important for health care professionals wanting to provide information to their patients or clients regarding their fitness level.

Submaximal and peak cardiorespiratory response after moderate-high intensity exercise training in subacute stroke.

PURPOSE: Reduced cardiovascular fitness post-stroke may negatively impact recovery. There is little information regarding exercise testing performance and cardiorespiratory response to an aerobic exercise intervention in subacute stroke. The purpose of this study was to examine cardiorespiratory response in subacute stroke after an 8-week aerobic exercise intervention using a total body recumbent stepper (TBRS). METHODS: Nine individuals with mean age 61.2 (SD 4.7) years and mean 66.7 (SD 41.5) days post-stroke completed the exercise intervention. Participants had a mean Fugl-Meyer score of 100.3 (SD 29.3). Outcome measures were obtained at baseline and postintervention. A peak exercise test using a TBRS assessed oxygen consumption, heart rate, and minute ventilation. Participants completed an 8-week exercise intervention on a recumbent stepper 3 times per week at a prescribed heart rate intensity. RESULTS: Submaximal VO2 was significantly lower from baseline to postintervention with a main effect of Study Visit (F1,8 = 8.5, p = 0.02). Heart rate was not significantly different pre- to postintervention. Minute ventilation exhibited no main effect of Study Visit or Test Minute. CONCLUSION: Moderate-high intensity aerobic exercise in subacute stroke appears to be beneficial for improving cardiovascular outcomes during submaximal performance of an exercise test.

Aerobic exercise in subacute stroke improves cardiovascular health and physical performance.

BACKGROUND AND PURPOSE: Cardiovascular health is often impaired after stroke. Reduced exercise capacity ((Equation is included in full-text article.)VO(2peak)) and changes in the vascular system in the stroke-affected limb may impact performance of physical activities such as walking. There is little information regarding the role of prescribed moderate- to high-intensity exercise in subacute stroke. The purpose of this study was to examine whether an 8-week aerobic exercise intervention would improve cardiovascular health and physical performance in participants with subacute stroke. METHODS: Ten subjects were enrolled in the study and 9 of them completed the intervention. Participants were aged 61.2 ± 4.7 years old, were 66.7 ± 41.5 days poststroke, and had minor motor performance deficits (Fugl-Meyer score, 100.3 ± 29.3). Outcome measures were taken at baseline, postintervention, and at 1-month follow-up. Brachial artery vasomotor reactivity (flow-mediated dilation [FMD]) of both arms was used to assess vascular health, and a peak exercise test was used to assess exercise capacity. The 6-minute walk test (6MWT) was used to assess physical performance. Participants exercised on a recumbent stepper 3 times per week for 8 weeks at a prescribed heart rate intensity. RESULTS: At baseline, we identified between-limb differences in brachial artery FMD and low (Equation is included in full-text article.)VO(2peak) values. After the intervention, significant improvements were observed in the FMD in both arms, resting systolic blood pressure, and the 6MWT. Although we also observed improvements in the resting diastolic blood pressure, heart rate, and (Equation is included in full-text article.)VO(2peak) values, these changes were not significantly different. DISCUSSION AND CONCLUSION: Aerobic exercise in participants with subacute stroke was beneficial for improving cardiovascular health, reducing cardiac risk, and improving physical performance (6MWT).

Measures of Cardiovascular Health and Physical Function after an Aerobic Exercise Intervention in a Patient Fifteen Days Post-Stroke.

Study Design: Case Study Background: Changes in cardiorespiratory (CR) fitness post-stroke severely impact an individual's quality of life. The purpose of this case study was to demonstrate whether a moderate to high intensity aerobic exercise program would improve cardiovascular fitness, and physical performance measures in a participant following discharge from acute stroke rehabilitation. The participant is a 58 year-old female who experienced an ischemic stroke 15 days prior to beginning the exercise intervention. Case Description: The participant was provided a supervised 8-week exercise intervention on a Total Body Recumbent Stepper (TBRS). The exercise intervention consisted of three sessions per week; the first 4 weeks the participant exercised at a moderate intensity of 50-59% heart rate reserve (HRR) calculated from the baseline exercise test; the last 4 weeks the intensity was increased to 60-69% HRR. Exercise duration began at 20 minutes with the goal of reaching 30 minutes of continuous exercise at a specified workload. Outcomes: Following 8-weeks of intervention, the participant showed improvement in cardiovascular measures including: resting blood pressure (BP), resting heart rate (HR), VO2 peak, and the maximum distance walked (6-MWT). Conclusion: The use of a moderate to high intensity aerobic exercise intervention may be effective for participants in the sub-acute phase of stroke recovery in order to improve cardiovascular health and physical function.