Background and Purpose Cardiovascular health is often impaired after stroke. Reduced exercise capacity (VO2 peak) and changes in the vascular system in the stroke-affected limb may impact physical performance such as walking. There is little information regarding the role of prescribed moderate-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. Methods Ten subjects were enrolled in the study and 9 completed the intervention. Participants were 61.2 ± 4.7 years old, 66.7 ± 41.5 days post-stroke and had minor motor performance deficits (Fugl-Meyer score, 100.3 ± 29.3). Outcome measures were taken at baseline, post-intervention and one-month follow-up. Brachial artery vasomotor reactivity (flow mediated dilation; FMD) of both arms assessed vascular health and a peak exercise test assessed exercise capacity. The six-minute walk (6-MWT) test was used to assess physical performance. Participants exercised on a recumbent stepper three times per week for eight weeks in a prescribed heart rate (HR) intensity. Results At baseline, we report between-limb differences in brachial artery FMD and low VO2 peak values. After the intervention, significant improvements were reported in FMD in both arms, resting systolic blood pressure (SBP) and the 6MWT. Although we also observed improvements in resting diastolic BP, HR and VO2 peak values, after the exercise intervention, these were not statistically significant Discussion and Conclusion Aerobic exercise in subacute stroke was beneficial for improving cardiovascular health, reducing cardiac risk and improving physical performance (6MWT).

Objective. Agonism of the protease activated receptor (PAR) 1 by activated protein C (APC) provides neuroprotection and vasculoprotection in experimental neuro-injury models. The pleiotropic PAR1 agonist, 3K3A-APC, reduces neurologic injury and promotes vascular integrity; 3K3A-APC proved safe in human volunteers. We performed a randomized, controlled, blinded, trial to determine the maximally tolerated dose (MTD) of 3K3A-APC in ischemic stroke patients. Methods. The NeuroNEXT trial RHAPSODY used a novel continual reassessment method to determine the MTD using tiers of 120, 240, 360 and 540 μg/kg 3K3A-APC. After intravenous tissue plasminogen activator, intraarterial mechanical thrombectomy, or both, patients were randomized to one of the four doses or placebo. Vasculoprotection was assessed as microbleed and intracranial hemorrhage (ICH) rates. Results. Between January 2015 and July 2017 we treated 110 patients. Demographics resembled a typical stroke population. The MTD was the highest dose 3K3A-APC tested, 540 μg/kg, with an estimated toxicity rate of 7%. There was no difference in prespecified ICH rates. In exploratory analyses, 3K3A-APC reduced ICH rates compared to placebo from 86.5% to 67.4% in the combined treatment arms (p=0.046), and total hemorrhage volume from an average of 2.1±5.8 mL in placebo to 0.8±2.1 mL in the combined treatment arms (p=0.066). Interpretation. RHAPSODY is the first trial of a neuroprotectant for acute ischemic stroke in a trial design allowing thrombectomy, thrombolysis, or both. The MTD was 540 μg/kg for the PAR1 active cytoprotectant 3K3A-APC. A trend toward lower hemorrhage rate in an exploratory analysis requires confirmation.

Background and Purpose Observational studies demonstrate low levels of physical activity during in-patient stroke rehabilitation. There is no objective measure of 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 males; 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 was assessed using the Physical Performance Test (PPT), Six-Minute Walk Test (6MWT), and Timed-Up and Go (TUG), 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 PPT performance at discharge (r = −0.37; p = 0.05), but not the 6MWT or TUG. 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 an emphasis towards increasing physical activity during the hospital stay. Video Abstract available for more insights from the authors (See Video, Supplemental Digital Content 1).