Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent and S-nitrosothiol mediated signal transduction.

Cerebral hypoxic vasodilation is poorly understood in humans, which undermines the development of therapeutics to optimize cerebral oxygen delivery. Across four investigations (total n = 195) we investigated the role of nitric oxide (NO) and hemoglobin-based S-nitrosothiol (RSNO) and nitrite (NO2-) signaling in the regulation of cerebral hypoxic vasodilation. We conducted hemodilution (n = 10) and NO synthase inhibition experiments (n = 11) as well as hemoglobin oxygen desaturation protocols, wherein we measured cerebral blood flow (CBF), intra-arterial blood pressure, and in subsets of participants trans-cerebral release/uptake of RSNO and NO2-. Higher CBF during hypoxia was associated with greater trans-cerebral RSNO release but not NO2-, while NO synthase inhibition reduced cerebral hypoxic vasodilation. Hemodilution increased the magnitude of cerebral hypoxic vasodilation following acute hemodilution, while in 134 participants tested under normal conditions, hypoxic cerebral vasodilation was inversely correlated to arterial hemoglobin concentration. These studies were replicated in a sample of polycythemic high-altitude native Andeans suffering from excessive erythrocytosis (n = 40), where cerebral hypoxic vasodilation was inversely correlated to hemoglobin concentration, and improved with hemodilution (n = 6). Collectively, our data indicate that cerebral hypoxic vasodilation is partially NO-dependent, associated with trans-cerebral RSNO release, and place hemoglobin-based NO signaling as a central mechanism of cerebral hypoxic vasodilation in humans.

Pelvis perturbations in various directions while standing in staggered stance elicit concurrent responses in both the sagittal and frontal plane.

Increasing knowledge on human balance recovery strategies is important for the development of balance assistance strategies using assistive devices like a powered lower-limb exoskeleton. One of the postures which is relevant for this scenario, but underexposed in research, is staggered stance, a posture with one foot in front. We therefore aimed to gain a better understanding of balance recovery in staggered stance. We studied balance responses at joint- and muscle levels to pelvis perturbations in various directions while standing in this posture. Ten healthy individuals participated in this study. We used one actuator beside and one behind the participant to apply 150 ms perturbations in mediolateral (ML), anteroposterior (AP) and diagonal directions, with a magnitude of 3, 6, 9 and 12% of the participant's body weight (BW). Meanwhile, motion capture, ground reaction forces and moments, and electromyography of the muscles around the ankles and hips were recorded. The perturbations caused movements of the centre of mass (CoM) and centre of pressure (CoP) in the direction of the perturbation. These were often accompanied by motions in a direction different from the perturbation direction. After perturbations perpendicular to the line between both feet, large and significant AP deviations were present of the CoM (-0.27 till 0.40 cm/%BW, p < 0.029) and CoP (-0.99 till 0.80 cm/%BW, p < 0.001). Also, stronger responses on joint and muscle level were present after these perturbations, compared to AP and diagonal perturbations collinear with the line between both feet. The hip, knee and ankle joints contributed differently to the balance responses after the different perturbation directions. To conclude, standing in a staggered stance posture makes individuals more vulnerable to perturbations perpendicular to the line between both feet, requiring larger responses on joint level as well as contributions in the sagittal plane.

Cooperative ankle-exoskeleton control can reduce effort to recover balance after unexpected disturbances during walking.

BACKGROUND: In the last two decades, lower-limb exoskeletons have been developed to assist human standing and locomotion. One of the ongoing challenges is the cooperation between the exoskeleton balance support and the wearer control. Here we present a cooperative ankle-exoskeleton control strategy to assist in balance recovery after unexpected disturbances during walking, which is inspired on human balance responses. METHODS: We evaluated the novel controller in ten able-bodied participants wearing the ankle modules of the Symbitron exoskeleton. During walking, participants received unexpected forward pushes with different timing and magnitude at the pelvis level, while being supported (Exo-Assistance) or not (Exo-NoAssistance) by the robotic assistance provided by the controller. The effectiveness of the assistive strategy was assessed in terms of (1) controller performance (Detection Delay, Joint Angles, and Exerted Ankle Torques), (2) analysis of effort (integral of normalized Muscle Activity after perturbation onset); and (3) Analysis of center of mass COM kinematics (relative maximum COM Motion, Recovery Time and Margin of Stability) and spatio-temporal parameters (Step Length and Swing Time). RESULTS: In general, the results show that when the controller was active, it was able to reduce participants' effort while keeping similar ability to counteract and withstand the balance disturbances. Significant reductions were found for soleus and gastrocnemius medialis activity of the stance leg when comparing Exo-Assistance and Exo-NoAssistance walking conditions. CONCLUSIONS: The proposed controller was able to cooperate with the able-bodied participants in counteracting perturbations, contributing to the state-of-the-art of bio-inspired cooperative ankle exoskeleton controllers for supporting dynamic balance. In the future, this control strategy may be used in exoskeletons to support and improve balance control in users with motor disabilities.