TY - JOUR A1 - Monti, Elena A1 - Waldvogel, Janice A1 - Ritzmann, Ramona A1 - Freyler, Kathrin A1 - Albracht, Kirsten A1 - Helm, Michael A1 - De Cesare, Niccolò A1 - Pavan, Piero A1 - Reggiani, Carlo A1 - Gollhofer, Albert A1 - Narici, Marco Vincenzo T1 - Muscle in variable gravity: “I do not know where I am, but I know what to do” JF - Frontiers in Physiology N2 - Performing tasks, such as running and jumping, requires activation of the agonist and antagonist muscles before (motor unit pre-activation) and during movement performance (Santello and Mcdonagh, 1998). A well-timed and regulated muscle activation elicits a stretch-shortening cycle (SSC) response, naturally occurring in bouncing movements (Ishikawa and Komi, 2004; Taube et al., 2012). By definition, the SSC describes the stretching of a pre-activated muscle-tendon complex immediately followed by a muscle shortening in the concentric push-off phase (Komi, 1984). Given the importance of SSC actions for human movement, it is not surprising that many studies investigated the biomechanics of this phenomenon; in particular, drop jumps (DJs) represent a good paradigm to study muscle fascicle and tendon behavior in ballistic movements involving the SSC. Within a DJ, three main phases [pre-activation, braking, and push-off (PO; Komi, 2000)] have been recognized and extensively studied in common and challenging conditions, such as changes in load, falling height, or simulated hypo-gravity (Avela et al., 1994; Arampatzis et al., 2001; Fukashiro et al., 2005; Ishikawa et al., 2005; Sousa et al., 2007; Ritzmann et al., 2016; Helm et al., 2020). These studies show that the timing and amount of triceps-surae muscle-tendon unit pre-activation in DJs are differentially regulated based on the load applied to the muscle, being optimal in normal “Earth” gravity conditions (Avela et al., 1994), but decreased in simulated hypo-gravity, hyper-gravity (Avela et al., 1994; Ritzmann et al., 2016), or unknown conditions (i.e., unknown falling heights; Helm et al., 2020). Some authors indicated that, when falling from heights different from the optimal one [defined as the drop height giving a maximum DJ performance indicated as peak ground reaction force (GRF) or jump high], electromyographic (EMG) activity of the plantar flexors increases from lower than optimal to higher than optimal heights (Ishikawa and Komi, 2004; Sousa et al., 2007). These findings highlight the ability of the central nervous system to regulate the timing and amount of pre-activation according to different jumping conditions, thus regulating muscle fascicle length, tendon and joint stiffness as well as position, in order to safely land on the ground and quickly re-bounce. Similarly, to pre-activation, also in the braking phase, the plantar flexors are differentially regulated. In optimal height (i.e., load) jumping conditions, gastrocnemius medialis (GM) fascicles shorten at early ground contact (possibly due to the intervention of the stretch reflex; Gollhofer et al., 1992) and behave quasi-isometrically in the late braking phase, enabling tendon elongation, and storage of elastic energy (Gollhofer et al., 1992; Fukashiro et al., 2005; Sousa et al., 2007). When increasing the falling height (augmenting the impact GRF), the quasi-isometric behavior of fascicles disappears, and fast fascicle lengthening occurs (Ishikawa et al., 2005; Sousa et al., 2007). In the third and last PO phase, fascicles shorten and the tendon releases the elastic energy previously stored. Bobbert et al. (1987) reported no influence of jumping height on the work done and on the net vertical impulse assessed during PO; this observation suggests that, despite an optimal DJ performance might be achieved only in specific conditions (falling heights, loads), the central nervous system seems to be able to regulate muscle behavior in order to effectively perform the required task also in challenging situations. Although the regulation of triceps-surae muscle-tendon unit in DJs has been extensively investigated, very few studies focused on sarcomeres behavior during the performance of this SSC movement (Kurokawa et al., 2003; Fukashiro et al., 2005, 2006). Sarcomeres represent muscle contractile units and are known to express different amounts of force depending on their length (Gordon et al., 1966; Walker and Schrodt, 1974); thus, understanding the time course of their responses during DJs is fundamental to gain further insights into muscle force-generating capacity. In vivo measurement of sarcomere length in humans has been so far been performed only in static positions and under highly controlled experimental conditions (Llewellyn et al., 2008; Sanchez et al., 2015). Instead, human sarcomere length estimation (achieved by dividing GM measured fascicle length for a fixed sarcomere number) in dynamic contractions provided an indirect measure of sarcomere operating range during squat jump, countermovement jump, and DJ (Fukashiro et al., 2005, 2006; Kurokawa et al., 2003). The results of these studies showed that sarcomeres operate in the ascending limb of their length-tension (L-T) relationship in all types of jumps, and particularly so in DJ. However, most of the available observations on sarcomere and muscle fascicle behavior were made in condition of constant gravity. Thus, in order to understand how sarcomere and muscle fascicle length are regulated in variable gravity conditions, we performed experiments in a parabolic flight, involving variable gravity levels, ranging from about zero-g to about double the Earth’s gravity (1 g; Waldvogel et al., 2021). Specifically, the aims of the present study were as follows: 1. To investigate the ability of the neuromuscular system in regulating fascicle length in response to conditions of variable gravity. 2. To estimate sarcomere operative length in the different DJ phases, in order to calculate its theoretical force production and its possible modulation in conditions of variable gravity. We hypothesized that muscle fascicles would be differentially regulated in different gravity conditions compared to 1 g, particularly in anticipation of landing and re-bouncing in unknown gravity levels. In addition, we hypothesized that sarcomeres would operate in the upper part of the ascending limb of their L-T relationship, possibly lengthening during the braking phase (especially in hyper-gravity) while operating quasi-isometrically in 1 g. KW - parabolic flight KW - drop jump KW - hypo-gravity KW - hyper-gravity KW - sarcomere operating length Y1 - 2021 U6 - https://doi.org/10.3389/fphys.2021.714655 SN - 1664-042X VL - 12 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Stäudle, Benjamin A1 - Seynnes, Olivier A1 - Laps, Guido A1 - Göll, Fabian A1 - Brüggemann, Gert-Peter A1 - Albracht, Kirsten T1 - Recovery from achilles tendon repair: a combination of Postsurgery Outcomes and Insufficient remodeling of muscle and tendon JF - Medicine & Science in Sports & Exercise N2 - Achilles tendon rupture (ATR) patients have persistent functional deficits in the triceps surae muscle–tendon unit (MTU). The complex remodeling of the MTU accompanying these deficits remains poorly understood. The purpose of the present study was to associate in vivo and in silico data to investigate the relations between changes inMTU properties and strength deficits inATR patients. Methods: Elevenmale subjects who had undergone surgical repair of complete unilateral ATR were examined 4.6 ± 2.0 (mean ± SD) yr after rupture. Gastrocnemius medialis (GM) tendon stiffness, morphology, and muscle architecture were determined using ultrasonography. The force–length relation of the plantar flexor muscles was assessed at five ankle joint angles. In addition, simulations (OpenSim) of the GM MTU force–length properties were performed with various iterations of MTU properties found between the unaffected and the affected side. Results: The affected side of the patients displayed a longer, larger, and stiffer GM tendon (13% ± 10%, 105% ± 28%, and 54% ± 24%, respectively) compared with the unaffected side. The GM muscle fascicles of the affected side were shorter (32% ± 12%) and with greater pennation angles (31% ± 26%). A mean deficit in plantarflexion moment of 31% ± 10% was measured. Simulations indicate that pairing an intact muscle with a longer tendon shifts the optimal angular range of peak force outside physiological angular ranges, whereas the shorter muscle fascicles and tendon stiffening seen in the affected side decrease this shift, albeit incompletely. Conclusions: These results suggest that the substantial changes in MTU properties found in ATR patients may partly result from compensatory remodeling, although this process appears insufficient to fully restore muscle function. KW - Tendon Rupture KW - Stiffness KW - Simulation KW - Muscle Force KW - Muscle Fascicle Y1 - 2021 U6 - https://doi.org/10.1249/MSS.0000000000002592 SN - 1530-0315 VL - 53 IS - 7 SP - 1356 EP - 1366 PB - American College of Sports Medicine CY - Philadelphia, Pa. ER - TY - JOUR A1 - Werkhausen, Amelie A1 - Albracht, Kirsten A1 - Cronin, Neil J A1 - Paulsen, Gøran A1 - Bojsen-Møller, Jens A1 - Seynnes, Olivier R T1 - Effect of training-induced changes in achilles tendon stiffness on muscle-tendon behavior during landing JF - Frontiers in physiology N2 - During rapid deceleration of the body, tendons buffer part of the elongation of the muscle-tendon unit (MTU), enabling safe energy dissipation via eccentric muscle contraction. Yet, the influence of changes in tendon stiffness within the physiological range upon these lengthening contractions is unknown. This study aimed to examine the effect of training-induced stiffening of the Achilles tendon on triceps surae muscle-tendon behavior during a landing task. Twenty-one male subjects were assigned to either a 10-week resistance-training program consisting of single-leg isometric plantarflexion (n = 11) or to a non-training control group (n = 10). Before and after the training period, plantarflexion force, peak Achilles tendon strain and stiffness were measured during isometric contractions, using a combination of dynamometry, ultrasound and kinematics data. Additionally, testing included a step-landing task, during which joint mechanics and lengths of gastrocnemius and soleus fascicles, Achilles tendon, and MTU were determined using synchronized ultrasound, kinematics and kinetics data collection. After training, plantarflexion strength and Achilles tendon stiffness increased (15 and 18%, respectively), and tendon strain during landing remained similar. Likewise, lengthening and negative work produced by the gastrocnemius MTU did not change detectably. However, in the training group, gastrocnemius fascicle length was offset (8%) to a longer length at touch down and, surprisingly, fascicle lengthening and velocity were reduced by 27 and 21%, respectively. These changes were not observed for soleus fascicles when accounting for variation in task execution between tests. These results indicate that a training-induced increase in tendon stiffness does not noticeably affect the buffering action of the tendon when the MTU is rapidly stretched. Reductions in gastrocnemius fascicle lengthening and lengthening velocity during landing occurred independently from tendon strain. Future studies are required to provide insight into the mechanisms underpinning these observations and their influence on energy dissipation. KW - achilles tendon KW - energy absorption KW - energy dissipation KW - mechanical buffer KW - stiffness Y1 - 2018 U6 - https://doi.org/10.3389/fphys.2018.00794 SN - 1664-042X IS - 9 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Yang, Peng-Fei A1 - Kriechbaumer, Andreas A1 - Albracht, Kirsten A1 - Sanno, Maximilian A1 - Ganse, Bergita A1 - Koy, Timmo A1 - Shang, Peng A1 - brüggemann, Gert-Peter A1 - Müller, Lars Peter A1 - Rittweger, Jörn T1 - A novel optical approach for assessing in vivo bone segment deformation and its application in muscle-bone relationship studies in humans JF - Journal of Orthopaedic Translation Y1 - 2014 U6 - https://doi.org/10.1016/j.jot.2014.07.078 SN - 2214-0328 SN - 2214-031X VL - 2 IS - 4 SP - 238 EP - 238 PB - Elsevier CY - Singapore ER - TY - JOUR A1 - Angermann, Susanne A1 - Günthner, Roman A1 - Hanssen, Henner A1 - Lorenz, Georg A1 - Braunisch, Matthias C. A1 - Steubl, Dominik A1 - Matschkal, Julia A1 - Kemmner, Stephan A1 - Hausinger, Renate A1 - Block, Zenonas A1 - Haller, Bernhard A1 - Heemann, Uwe A1 - Kotliar, Konstantin A1 - Grimmer, Timo A1 - Schmaderer, Christoph T1 - Cognitive impairment and microvascular function in end-stage renal disease JF - International Journal of Methods in Psychiatric Research (MPR) N2 - Objective Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels. Methods 152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions. Results In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained. Conclusion This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention. KW - cerebral small vessel disease KW - cognitive impairment KW - dialysis KW - retinal vessels Y1 - 2022 U6 - https://doi.org/10.1002/mpr.1909 SN - 1049-8931 (Print) SN - 1557-0657 (Online) VL - 31 IS - 2 SP - 1 EP - 10 PB - Wiley ER - TY - JOUR A1 - Kotliar, Konstantin A1 - Ortner, Marion A1 - Conradi, Anna A1 - Hacker, Patricia A1 - Hauser, Christine A1 - Günthner, Roman A1 - Moser, Michaela A1 - Muggenthaler, Claudia A1 - Diehl-Schmid, Janine A1 - Priller, Josef A1 - Schmaderer, Christoph A1 - Grimmer, Timo T1 - Altered retinal cerebral vessel oscillation frequencies in Alzheimer's disease compatible with impaired amyloid clearance JF - Neurobiology of Aging N2 - Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis. KW - Alzheimer's disease KW - Retinal vessel analysis KW - Vasomotions KW - Pulsations KW - Mild cognitive impairment Y1 - 2022 U6 - https://doi.org/10.1016/j.neurobiolaging.2022.08.012 SN - 0197-4580 VL - 120 SP - 117 EP - 127 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Neumaier, Felix A1 - Weiss, Miriam A1 - Veldeman, Michael A1 - Kotliar, Konstantin A1 - Wiesmann, Martin A1 - Schulze-Steinen, Henna A1 - Höllig, Anke A1 - Clusmann, Hans A1 - Schubert, Gerrit Alexander A1 - Albanna, Walid T1 - Changes in endogenous daytime melatonin levels after aneurysmal subarachnoid hemorrhage – preliminary findings from an observational cohort study JF - Clinical Neurology and Neurosurgery N2 - Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH. KW - constructive alignment KW - examination KW - long-term retention KW - multimodal KW - practical learning Y1 - 2021 U6 - https://doi.org/10.1016/j.clineuro.2021.106870 SN - 0303-8467 VL - 208 IS - Article No.: 106870 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kuchler, Timon A1 - Günthner, Roman A1 - Ribeiro, Andrea A1 - Hausinger, Renate A1 - Streese, Lukas A1 - Wöhnl, Anna A1 - Kesseler, Veronika A1 - Negele, Johanna A1 - Assali, Tarek A1 - Carbajo-Lozoya, Javier A1 - Lech, Maciej A1 - Adorjan, Kristina A1 - Stubbe, Hans Christian A1 - Hanssen, Henner A1 - Kotliar, Konstantin A1 - Haller, Berhard A1 - Heemann, Uwe A1 - Schmaderer, Christoph T1 - Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation N2 - Background Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. Methods In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204). Measurements and main results PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. Conclusion Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management. KW - Endothelial dysfunction KW - Long COVID KW - Post-COVID-19 syndrome KW - retinal microvasculature Y1 - 2023 U6 - https://doi.org/10.1007/s10456-023-09885-6 N1 - Corresponding author: Christoph Schmaderer VL - 26 SP - 547 EP - 563 PB - Springer Nature CY - Dordrecht ER - TY - JOUR A1 - Kuerten, David A1 - Kotliar, Konstantin A1 - Fuest, Matthias A1 - Walter, Peter A1 - Hollstein, Muriel A1 - Plange, Niklas ED - Neri, Piergiorgio T1 - Does hemispheric vascular regulation differ significantly in glaucoma patients with altitudinal visual field asymmetry? A single-center, prospective study JF - International Ophthalmology N2 - Purpose Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. Methods 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 pro- found hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. Results Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p \ 0.04 and p \ 0.02 respectively) in-between the hemispheres spheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. Conclusion Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetri altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect. KW - Glaucoma KW - Visual field asymmetry KW - Ocular blood flow KW - RVA KW - Vascular response Y1 - 2021 SN - 1573-2630 U6 - https://doi.org/10.1007/s10792-021-01876-0 VL - 41 IS - 41 SP - 3109 EP - 3119 PB - Springer CY - Berlin ER - TY - JOUR A1 - Albanna, Walid A1 - Conzen, Catharina A1 - Weiss, Miriam A1 - Seyfried, Katharina A1 - Kotliar, Konstantin A1 - Schmidt, Tobias Philip A1 - Kuerten, David A1 - Hescheler, Jürgen A1 - Bruecken, Anne A1 - Schmidt-Trucksäss, Arno A1 - Neumaier, Felix A1 - Wiesmann, Martin A1 - Clusmann, Hans A1 - Schubert, Gerrit Alexander T1 - Non-invasive assessment of neurovascular coupling after aneurysmal subarachnoid hemorrhage: a prospective observational trial using retinal vessel analysis JF - Frontiers in Neurology N2 - Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus. Y1 - 2021 U6 - https://doi.org/10.3389/fneur.2021.690183 SN - 1664-2295 VL - 12 IS - 12 SP - 1 EP - 15 ER -