Lower dynamic cerebral autoregulation following acute bout of low-volume high-intensity interval exercise in chronic stroke compared to healthy adults.

Fluctuating arterial blood pressure during high-intensity interval exercise (HIIE) may challenge dynamic cerebral autoregulation (dCA), specifically after stroke after an injury to the cerebrovasculature. We hypothesized that dCA would be attenuated at rest and during a sit-to-stand transition immediately after and 30 min after HIIE in individuals poststroke compared with age- and sex-matched control subjects (CON). HIIE switched every minute between 70% and 10% estimated maximal watts for 10 min. Mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) were recorded. dCA was quantified during spontaneous fluctuations in MAP and MCAv via transfer function analysis. For sit-to-stand, time delay before an increase in cerebrovascular conductance index (CVCi = MCAv/MAP), rate of regulation, and % change in MCAv and MAP were measured. Twenty-two individuals poststroke (age 60 ± 12 yr, 31 ± 16 mo) and twenty-four CON (age 60 ± 13 yr) completed the study. Very low frequency (VLF) gain (P = 0.02, η2 = 0.18) and normalized gain (P = 0.01, η2 = 0.43) had a group × time interaction, with CON improving after HIIE whereas individuals poststroke did not. Individuals poststroke had lower VLF phase (P = 0.03, η2 = 0.22) after HIIE compared with CON. We found no differences in the sit-to-stand measurement of dCA. Our study showed lower dCA during spontaneous fluctuations in MCAv and MAP following HIIE in individuals poststroke compared with CON, whereas the sit-to-stand response was maintained.NEW & NOTEWORTHY This study provides novel insights into poststroke dynamic cerebral autoregulation (dCA) following an acute bout of high-intensity interval exercise (HIIE). In people after stroke, dCA appears attenuated during spontaneous fluctuations in mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) following HIIE. However, the dCA response during a single sit-to-stand transition after HIIE showed no significant difference from controls. These findings suggest that HIIE may temporarily challenge dCA after exercise in individuals with stroke.

Aerobic Exercise Improves Cortical Inhibitory Function After Stroke: A Preliminary Investigation.

BACKGROUND AND PURPOSE: Aerobic exercise can elicit positive effects on neuroplasticity and cognitive executive function but is poorly understood after stroke. We tested the effect of 4 weeks of aerobic exercise training on inhibitory and facilitatory elements of cognitive executive function and electroencephalography markers of cortical inhibition and facilitation. We investigated relationships between stimulus-evoked cortical responses, blood lactate levels during training, and aerobic fitness postintervention. METHODS: Twelve individuals with chronic (>6 months) stroke completed an aerobic exercise intervention (40 minutes, 3×/wk). Electroencephalography and motor response times were assessed during congruent (response facilitation) and incongruent (response inhibition) stimuli of a Flanker task. Aerobic fitness capacity was assessed as o2peak during a treadmill test pre- and postintervention. Blood lactate was assessed acutely (<1 minute) after exercise each week. Cortical inhibition (N2) and facilitation (frontal P3) were quantified as peak amplitudes and latencies of stimulus-evoked electroencephalographic activity over the frontal cortical region. RESULTS: Following exercise training, the response inhibition speed increased while response facilitation remained unchanged. A relationship between earlier cortical N2 response and faster response inhibition emerged postintervention. Individuals who produced higher lactate during exercise training achieved faster response inhibition and tended to show earlier cortical N2 responses postintervention. There were no associations between o2peak and metrics of behavioral or neurophysiologic function. DISCUSSION AND CONCLUSIONS: These preliminary findings provide novel evidence for selective benefits of aerobic exercise on inhibitory control during the initial 4-week period after initiation of exercise training and implicate a potential therapeutic effect of lactate on poststroke inhibitory control.

Lower middle cerebral artery blood velocity during low-volume high-intensity interval exercise in chronic stroke.

High-intensity interval training (HIIE) may present unique challenges to the cerebrovascular system in individuals post-stroke. We hypothesized lower middle cerebral artery blood velocity (MCAv) in individuals post-stroke: 1) during 10 minutes of HIIE, 2) immediately following HIIE, and 3) 30 minutes after HIIE, compared to age- and sex-matched controls (CON). We used a recumbent stepper submaximal exercise test to determine workloads for high-intensity and active recovery. Our low volume HIIE protocol consisted of 1-minute intervals for 10 minutes. During HIIE, we measured MCAv, mean arterial pressure (MAP), heart rate (HR), and end tidal carbon dioxide (PETCO2). We assessed carotid-femoral pulse wave velocity as a measure of arterial stiffness. Fifty participants completed the study (25 post-stroke, 76% ischemic, 32% moderate disability). Individuals post-stroke had lower MCAv during HIIE compared to CON (p = 0.03), which remained 30 minutes after HIIE. Individuals post-stroke had greater arterial stiffness (p = 0.01) which was moderately associated with a smaller MCAv responsiveness during HIIE (r = -0.44). No differences were found for MAP, HR, and PETCO2. This study suggests individuals post-stroke had a lower MCAv during HIIE compared to their peers, which remained during recovery up to 30 minutes. Arterial stiffness may contribute to the lower cerebrovascular responsiveness post-stroke.

Force sensor reduced measurement error compared with verbal command during sit-to-stand assessment of cerebral autoregulation.

Current methods estimate the time delay (TD) before the onset of dynamic cerebral autoregulation (dCA) from verbal command to stand. A force sensor used during a sit-to-stand dCA measure provides an objective moment an individual stands (arise-and-off, AO). We hypothesized that the detection of AO would improve the accuracy of TD compared with estimation. We measured middle cerebral artery blood velocity (MCAv) and mean arterial pressure (MAP) for 60 s sitting followed by 2-min standing, three times separated by 20 min. TD was calculated as the time from: (1) verbal command and (2) AO, until an increase in cerebrovascular conductance index (CVCi = MCAv/MAP). Sixty-five participants were enrolled: young adults (n = 25), older adults (n = 20), and individuals post-stroke (n = 20). The TD calculated from AO ( x ¯ $$ \overline{x} $$ = 2.98 ± 1.64 s) was shorter than TD estimated from verbal command ( x ¯ $$ \overline{x} $$ = 3.35 ± 1.72 s, η2 = 0.49, p < 0.001), improving measurement error by ~17%. TD measurement error was not related to age or stroke. Therefore, the force sensor provided an objective method to improve the calculation of TD compared with current methods. Our data support using a force sensor during sit-to-stand dCA measures in adults across the lifespan and post-stroke.

Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial.

Importance: For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. Objective: To assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke. Design, Setting, and Participants: This multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled. Interventions: Participants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated. Main Outcomes and Measures: The main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training. Results: Of 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, -9 to 33 m]; mean difference, 15 m [95% CI, -13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue. Conclusions and Relevance: These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains. Trial Registration: ClinicalTrials.gov Identifier: NCT03760016.

Secondary Analysis of Walking Activities during the Acute Stroke Hospital Stay and Cerebrovascular Health.

Purpose: Physical activity within the hospital post-stroke is recommended for cardiovascular and musculoskeletal health, but no studies have examined cerebrovascular health. We hypothesized individuals who walked farther distances (FARhigh) during the acute phase of stroke recovery in a hospital setting would have a higher resting middle cerebral artery blood velocity (MCAv) and a greater cerebrovascular response (CVR) to moderate-intensity exercise at 3-months post-stroke, compared to individuals who walked shorter distances (FARlow). Methods: At 3-month post-stroke, we recorded 90-seconds of resting baseline (BL) MCAv followed by 6-minutes of moderate-intensity exercise. We calculated CVR as the change in MCAv from BL to steady-state exercise. We retrospectively collected farthest distance walked within the hospital post-stroke from the electronic medical record. Participants were classified as FARhigh or FARlow based on average farthest walking distance. Results: Twenty participants completed the study, age 63 (15) years. BL MCAv was not different between groups (p = 0.07). In comparison to FARlow, we report a higher CVR in FARhigh's ipsilesional ( x ¯ = 7.38 (5.42) vs x ¯ = 2.19 (3.53), p = 0.02) and contralesional hemisphere ( x ¯ = 8.15 (6.37) vs x ¯ = 2.06 (4.76), p = 0.04). Conclusions: Physical activity during the hospital stay post-stroke may support cerebrovascular health after discharge. Prospective studies are needed to support this finding.

Novel application of a force sensor during sit-to-stands to measure dynamic cerebral autoregulation onset.

Current sit-to-stand methods measuring dynamic cerebral autoregulation (dCA) do not capture the precise onset of the time delay (TD) response. Reduced sit-to-stand reactions in older adults and individuals post-stroke could inadvertently introduce variability, error, and imprecise timing. We applied a force sensor during a sit-to-stand task to more accurately determine how TD before the onset of dCA may be altered. Middle cerebral artery blood velocity (MCAv) and mean arterial pressure (MAP) were measured during two sit-to-stands separated by 15 min. Recordings started with participants sitting on a force-sensitive resistor for 60 s, then asked to stand for 2 min. Upon standing, the force sensor voltage immediately dropped and marked the exact moment of arise-and-off (AO). Time from AO until an increase in cerebrovascular conductance (CVC = MCAv/MAP) was calculated as TD. We tested the sensor in four healthy young adults, two older adults, and two individuals post-stroke. Healthy young adults stood quickly and the force sensor detected a small change in TD compared to classically estimated AO, from verbal command to stand. When compared to the estimated AO, older adults had a delayed measured AO and TD decreased up to ~53% while individuals post-stroke had an early AO and TD increased up to ~14%. The stance time during the sit-to-stand has the potential to influence the TD before the onset of dCA metric. As observed in the older adults and participants with stroke, this response may drastically vary and influence TD.

Cerebrovascular response to an acute bout of low-volume high-intensity interval exercise and recovery in young healthy adults.

High-intensity interval exercise (HIIT) is performed widely. However, there is a gap in knowledge regarding the acute cerebrovascular response to low-volume HIIT. Our objective was to characterize the middle cerebral artery blood velocity (MCAv) response during an acute bout of low-volume HIIT in young healthy adults. We hypothesized that MCAv would decrease below the baseline (BL), 1) during HIIT, 2) immediately following HIIT, and 3) 30 min after HIIT. As a secondary objective, we investigated sex differences in the MCAv response during HIIT. Twenty-four young healthy adults completed HIIT [12 males, age = 25 (SD = 2)]. HIIT included 10 min of 1-min high intensity (∼70% estimated maximal Watts) and active recovery (10% estimated maximal Watts) intervals on a recumbent stepper. MCAv, mean arterial pressure (MAP), heart rate (HR), and end-tidal carbon dioxide ([Formula: see text]) were recorded at BL, during HIIT, immediately following HIIT, and 30 min after HIIT. Contrary to our hypothesis, MCAv remained above BL during HIIT. MCAv peaked at minute 3 then decreased concomitantly with [Formula: see text]. MCAv was lower than BL immediately following HIIT (P < 0.001). Thirty minutes after HIIT, MCAv returned to BL (P = 0.47). Compared with men, women had a higher MCAv at BL (P = 0.001), during HIIT (P = 0.009), immediately following HIIT (P = 0.004), and 30 min after HIIT (P = 0.001). MCAv did not decrease below BL during low-volume HIIT. However, MCAv decreased below BL immediately following HIIT and returned to resting values 30 min after HIIT. MCAv also differed between sexes.NEW & NOTEWORTHY We are the first, to our knowledge, to characterize the cerebrovascular and hemodynamic response to low-volume high-intensity interval exercise (HIIT, 1-min intervals) in young healthy adults. Middle cerebral artery blood velocity (MCAv) decreased during the HIIT bout and rebounded during active recovery. Women demonstrated a significantly higher resting MCAv than men and the difference remained during HIIT. Here, we report a novel protocol and characterized the MCAv response during an acute bout of low-volume HIIT.

Pilot Study to Characterize Middle Cerebral Artery Dynamic Response to an Acute Bout of Moderate Intensity Exercise at 3- and 6-Months Poststroke.

Background The primary aim of this study was to characterize the middle cerebral artery blood velocity (MCAv) dynamic response to an acute bout of exercise in humans at 3- and 6-months poststroke. As a secondary objective, we grouped individuals according to the MCAv dynamic response to the exercise bout as responder or nonresponder. We tested whether physical activity, aerobic fitness, and exercise mean arterial blood pressure differed between groups. Methods and Results Transcranial Doppler ultrasound measured MCAv during a 90-second baseline followed by a 6-minute moderate intensity exercise bout. Heart rate, mean arterial blood pressure, and end-tidal CO2 were additional variables of interest. The MCAv dynamic response variables included the following: baseline, time delay, amplitude, and time constant. Linear mixed model revealed no significant differences in our selected outcomes between 3- and 6-months poststroke. Individuals characterized as responders demonstrated a faster time delay, higher amplitude, and reported higher levels of physical activity and aerobic fitness when compared with the nonresponders. No between-group differences were identified for baseline, time constant, or exercise mean arterial blood pressure. In the nonresponders, we observed an immediate rise in MCAv following exercise onset followed by an immediate decline to near baseline values, while the responders showed an exponential rise until steady state was reached. Conclusions The MCAv dynamic response profile has the potential to provide valuable information during an acute exercise bout following stroke. Individuals with a greater MCAv response to the exercise stimulus reported statin use and regular participation in exercise.

Optimizing Recruitment Strategies and Physician Engagement for Stroke Recovery Research.

BACKGROUND AND PURPOSE: A major challenge for stroke rehabilitation and recovery research is the recruitment and retention of participants. Our prior challenges and successes have influenced our team to rethink our approach and the potential for large-scale stroke recruitment. SUMMARY OF KEY POINTS: In this special interest article, we highlight how the adoption and implementation of recruitment strategies such as physician engagement and a streamlined "customer service" approach helped us improve our enrollment and maximize efficiency. Another positive outcome of enrollment was increased representation of those who identify as underrepresented minority or live in rural areas. RECOMMENDATIONS FOR CLINICAL PRACTICE: Rethinking our recruitment processes and infrastructure allowed for greater interprofessional interactions, minimal burden for our stroke physician team members, and maximized enrollment into our stroke studies.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A324).

Effects of high intensity interval exercise on cerebrovascular function: A systematic review.

High intensity interval exercise (HIIE) improves aerobic fitness with decreased exercise time compared to moderate continuous exercise. A gap in knowledge exists regarding the effects of HIIE on cerebrovascular function such as cerebral blood velocity and autoregulation. The objective of this systematic review was to ascertain the effect of HIIE on cerebrovascular function in healthy individuals. We searched PubMed and the Cumulative Index to Nursing and Allied Health Literature databases with apriori key words. We followed the Preferred Reporting Items for Systematic Reviews. Twenty articles were screened and thirteen articles were excluded due to not meeting the apriori inclusion criteria. Seven articles were reviewed via the modified Sackett's quality evaluation. Outcomes included middle cerebral artery blood velocity (MCAv) (n = 4), dynamic cerebral autoregulation (dCA) (n = 2), cerebral de/oxygenated hemoglobin (n = 2), cerebrovascular reactivity to carbon dioxide (CO2) (n = 2) and cerebrovascular conductance/resistance index (n = 1). Quality review was moderate with 3/7 to 5/7 quality criteria met. HIIE acutely lowered exercise MCAv compared to moderate intensity. HIIE decreased dCA phase following acute and chronic exercise compared to rest. HIIE acutely increased de/oxygenated hemoglobin compared to rest. HIIE acutely decreased cerebrovascular reactivity to higher CO2 compared to rest and moderate intensity. The acute and chronic effects of HIIE on cerebrovascular function vary depending on the outcomes measured. Therefore, future research is needed to confirm the effects of HIIE on cerebrovascular function in healthy individuals and better understand the effects in individuals with chronic conditions. In order to conduct rigorous systematic reviews in the future, we recommend assessing MCAv, dCA and CO2 reactivity during and post HIIE.

The Effect of Stroke on Middle Cerebral Artery Blood Flow Velocity Dynamics During Exercise.

BACKGROUND AND PURPOSE: Previous work demonstrates that older adults have a lower response in the middle cerebral artery velocity (MCAv) to an acute bout of moderate-intensity exercise when compared with young adults. However, no information exists regarding MCAv response to exercise after stroke. We tested whether MCAv response to an acute bout of moderate-intensity exercise differed between participants 3 months after stroke and an age- and sex-matched control group of older adults (CON). A secondary objective was to compare MCAv response between the stroke- and non-stroke-affected MCAv. METHODS: Using transcranial Doppler ultrasound, we recorded MCAv during a 90-second baseline (BL) followed by a 6-minute moderate-intensity exercise bout using a recumbent stepper. Heart rate (HR), end-tidal CO2 (PETCO2), and beat-to-beat mean arterial blood pressure (MAP) were additional variables of interest. The MCAv response measures included BL, peak response amplitude (Amp), time delay (TD), and time constant (τ). RESULTS: The Amp was significantly lower in the stroke-affected MCAv compared with CON (P < 0.01) and in the nonaffected MCAv compared with CON (P = 0.03). No between-group differences were found between TD and τ. No significant differences were found during exercise for PETCO2 and MAP while HR was lower in participants with stroke (P < 0.01). Within the group of participants with stroke, no differences were found between the stroke-affected and non-stroke-affected sides for any measures. DISCUSSION AND CONCLUSIONS: Resolution of the dynamic response profile has the potential to increase our understanding of the cerebrovascular control mechanisms and test cerebrovascular response to physical therapy-driven interventions such as exercise.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A284).

Time Course of Flow-Mediated Dilation and Vascular Endothelial Growth Factor following Acute Stroke.

OBJECTIVES: People after stroke demonstrate alterations in vascular endothelial function measured by flow-mediated dilation. Limited information is available in the literature on possible protective factors following stroke. The aims of the secondary analysis were (1) to characterize the time course of vascular endothelial function using flow-mediated dilation at 72 hours after stroke and 1 week later during inpatient stroke rehabilitation and (2) to determine whether flow-mediated dilation was related to vascular endothelial growth factor, brain-derived neurotrophic factor, or estimated prestroke peak oxygen uptake. METHODS: Flow-mediated dilation using Doppler ultrasound was assessed in bilateral brachial arteries at the defined time points. Flow-mediated dilation and blood draws occurred on the same day between 7:30 am and 9:00 am following an overnight fast. Enzyme-linked immunosorbent assay was used to quantify plasma vascular endothelial growth factor and brain-derived neurotrophic factor values. A nonexercise estimate was used to calculate prestroke peak oxygen uptake. RESULTS: We have shown that between-limb differences are evident within 72 hours after stroke and remain 1 week later during inpatient rehabilitation. Higher values for vascular endothelial growth factor were associated with increased flow-mediated dilation at both time points. Higher estimated prestroke peak oxygen uptake was related to flow-mediated dilation. Brain-derived neurotrophic factor was not related to any outcome measures. CONCLUSIONS: Unique vascular adaptations start early after stroke in the stroke-affected limb and remain through inpatient stroke rehabilitation. Vascular endothelial growth factor and prestroke physical activity may have a protective role in vascular function following stroke. Future work should focus on mechanistic pathways for preservation of vascular health.