Calf Pump Research Articles

Investigating Skeletal Muscle Pump Function Using Thigh EMG, Thigh NIRS, And Stroke Volume Data In The FRAILMatics Physiological Cohort

Abstract Background The pioneering female physiologist Frances Hellebrandt first highlighted the significance of the skeletal muscle pump in circulation in the 1930s. However, the mechanisms underlying the muscle pump's function remain elusive, particularly in older individuals. It is thought that during muscle contraction, increased intramuscular pressure facilitates the expulsion of blood from the muscle's veins, aiding venous return. This contraction-induced pressure gradient assists in pushing blood towards the heart, increasing preload, and subsequently stroke volume (SV). In this study we investigated muscle pump activity using continuous measurements of thigh muscle activity, thigh total haemoglobin concentration (Hb), and cardiac SV. Methods 22 individuals (aged 70.8±5.3 years, 77.3% female) recruited from a Falls and Syncope Unit (St James’s Hospital, Dublin) underwent non-invasive measurements of Hb (NIRS PortaLite, Artinis Medical Systems, The Netherlands), electromyography (EMG) (Shimmer3, Research Ltd, Ireland), and SV (Finapres Nova, Finapres Medical Systems, The Netherlands) during a 10-second thigh squeeze test. Pre-processing involved data quality checks, alignment, and resampling. 60-second regions of interest were extracted, normalised, and processed using MATLAB (R2023a, TheMathWorks, Inc., Natick, MA, USA). Cross-correlation and Granger causality analyses were conducted to explore relationships between signals. Results Thigh Hb and EMG signals lagged 8.4 and 8.5 seconds behind SV, respectively. Granger Causality analysis revealed a significant causal relationship from both Hb and EMG to SV in 68% of participants at measured lags. Conclusion The observed ~8.5-second lag between thigh measurements and SV implies a plausible temporal relationship between muscle activation and venous return, further supported by significant causal relationships found in a substantial portion of participants using Granger causality analysis. These findings underscore the importance of continued research in this area, not only for advancing our understanding of physiological mechanisms but also for informing potential clinical applications aimed at optimising cardiovascular health and function.

The Efficacy of Multi-Layer Compression System and TIME-Concept for the Management of Leg Ulcers in Patients with Ambulatory Venous Hypertension – Truth and Myth

Introduction: Venous leg ulcers are late manifestations of chronic venous insufficiency that can cause disability and serious complications. The elderly are more commonly affected. This study was designed to test the effectiveness, healing rates, quality of life and costs of multi-layer compression system and TIME-concept (tissue management, infection control, moisture balance and wound edge optimization) for the management of leg ulcers in patients with ambulatory venous hypertension.Methods: A prospective clinical study on 50 outpatients with venous leg ulcers, treated three times weekly for 12 weeks or until healed, with all patients consenting and independently mobile associated with a multi-layer compression system along with the TIME-concept treatment.Results: The study revealed that, the cohort was predominantly female (66%) with a mean age of 61.7 years. Universal presence of varicose veins and secondary lymphedema was noted. Specific conditions included postthrombotic syndrome (24%), calf pump dysfunction (8%), and venectomy history (32%). All patients achieved complete epithelialization, with an average healing time of 8.5±8.3 weeks and a median of 5.5 weeks (P=0.0064), with 88% healing within 12 weeks. No significant complications were reported. The median number of clinic visits was 16.5, and the median treatment cost was UAH 11,240.00. Patients’ satisfaction with the treatment was 100% according to completed wound healing.Conclusions: The study demonstrates effective management of venous leg ulcers using a multi-layer compression system and the TIME concept, achieving high healing rates with minimal complications and manageable treatment costs.

Effect of Acute Dietary Nitrate Supplementation on the Changes in Calf Venous Volume during Postural Change and Skeletal Muscle Pump Activity in Healthy Young Adults.

Dietary nitrate (NO3-) supplementation is known to enhance nitric oxide (NO) activity and acts as a vasodilator. In this randomized crossover study, we investigated the effect of inorganic NO3- supplementation on the changes in calf venous volume during postural change and subsequent skeletal muscle pump activity. Fifteen healthy young adults were assigned to receive beetroot juice (BRJ) or a NO3--depleted control beverage (prune juice: CON). Two hours after beverage consumption, the changes in the right calf volume during postural change from supine to upright and a subsequent right tiptoe maneuver were measured using venous occlusion plethysmography. The increase in calf volume from the supine to upright position (total venous volume [VV]) and the decrease in calf volume during the right tiptoe maneuver (venous ejection volume [Ve]) were calculated. Plasma NO3- concentration was higher in the BRJ group than in the CON group 2 h after beverage intake (p < 0.05). However, VV and Ve did not differ between CON and BRJ. These results suggest that acute intake of BRJ may enhance NO activity via the NO3- → nitrite → NO pathway but does not change calf venous pooling due to a postural change or the calf venous return due to skeletal muscle pump activity in healthy young adults.

Live to Move and Move to Live: The Health of the Lymphatic System Relies on Mobility and the Foot and Calf Pump Connection

The foot and calf muscle pump, collectively known as the venous muscle pump, plays a crucial role in the circulatory system (veins, arteries, and lymphatics), particularly in the return of blood from the lower extremities to the heart. Further, the venous muscle pump is crucial to lymphatic health and essential in chronic edema/lymphedema management. This article will highlight the significance of the venous pump and review the functional anatomy and physiology of the foot and calf, integrating the connection to venous and lymphatic health. The complementary importance of mobility, exercise, and breathing will also be explored.

Haemodynamic Parameters Underlying the Relationship between Sarcopenia and Blood Pressure Recovery on Standing.

Sarcopenia, delayed blood pressure (BP) recovery following standing, and orthostatic hypotension (OH) pose significant clinical challenges associated with ageing. While prior studies have established a link between sarcopenia and impaired BP recovery and OH, the underlying haemodynamic mechanisms remain unclear. We enrolled 107 participants aged 50 and above from a falls and syncope clinic, conducting an active stand test with continuous non-invasive haemodynamic measurements. Hand grip strength and five-chair stand time were evaluated, and muscle mass was estimated using bioelectrical impedance analysis. Participants were categorised as non-sarcopenic or sarcopenic. Employing mixed-effects linear regression, we modelled the effect of sarcopenia on mean arterial pressure and heart rate after standing, as well as Modelflow®-derived parameters such as cardiac output, total peripheral resistance, and stroke volume, while adjusting for potential confounders. Sarcopenia was associated with diminished recovery of mean arterial pressure during the 10-20 s period post-standing (β -0.67, p < 0.001). It also resulted in a reduced ascent to peak (0-10 s) and recovery from peak (10-20 s) of cardiac output (β -0.05, p < 0.001; β 0.06, p < 0.001). Furthermore, sarcopenia was associated with attenuated recovery (10-20 s) of total peripheral resistance from nadir (β -0.02, p < 0.001) and diminished recovery from peak (10-20 s) of stroke volume (β 0.54, p < 0.001). Notably, heart rate did not exhibit a significant association with sarcopenia status at any time interval post-standing. The compromised BP recovery observed in sarcopenia appears to be driven by an initial reduction in the peak of cardiac output, followed by attenuated recovery of cardiac output from its peak and total peripheral resistance from its nadir. This cardiac output finding seems to be influenced by stroke volume rather than heart rate. Possible mechanisms for these findings include cardio-sarcopenia, the impact of sarcopenia on the autonomic nervous system, and/or the skeletal muscle pump.

The effect of lower limb strengthening exercise on orthostatic blood pressure and the skeletal muscle pump in older people with orthostatic hypotension.

Activation of muscles during standing is recommended to activate the skeletal muscle pump, increasing venous return and increasing blood pressure (BP) in people with orthostatic hypotension (OH). The aim of this study is to determine if increasing the strength of the lower limb muscles can improve the effectiveness of the venous pump and postural BP in older people with OH. Ten older people with OH underwent an 8-week lower limb strengthening intervention. Repeated measurements of orthostatic BP, calf venous ejection fraction (EF) and muscle strength took place before, during and after intervention. The intervention increased calf muscle strength by 21% (interquartile range: 18-28), p = 0.018, from a median baseline of 38 (34-45) kg. Participants had normal levels of venous EF 64% (51-75) at baseline, with little to no venous reflux. The median ejection volume at baseline was 44 (36-58) mL per calf. Despite increasing muscle strength, venous EF did not increase (percentage change -10% (-16 to 24), p = 0.8) and systolic BP drop did not improve (percentage change 0% (-17 to 16), p = 1.0). Similarly, visual analysis of individual case-series trends revealed increasing muscle strength with no clinically meaningful change in EF or orthostatic BP. Muscle strengthening exercise does not increase the effectiveness of the skeletal muscle pump and is not an efficacious intervention for OH. As there is little to no venous pooling in the calf during standing in older people with OH, below knee compression is unlikely to be clinically effective.

Unraveling the pathophysiology of lower-limb postthrombotic syndrome in adolescents: a proof-of-concept study.

A better understanding of the pathophysiology of pediatric postthrombotic syndrome (PTS) is needed to develop strategies to treat this condition. We investigated calf pump function, exercise capacity, balance in power output, and changes in limb muscle oxygen saturation (SmO2) and fluid content during exercise in 10 pediatric patients with unilateral lower-limb PTS, and in age- and sex-matched controls (1:1-1:2 ratio). Outcomes were investigated usingbioimpedance spectroscopy, torque-sensing pedals, and near-infrared spectroscopy during incremental- and constant-load cycling tests. The median age at participation was 17years (25th-75th percentile, 15-18 years); 68% of participants were females. The median CAPTSure score in the affected leg of affected participants was 35 points (25th-75th percentile, 24-46 points), indicating moderate/severe PTS; 20% of patients had a history of central venous catheter-related thrombosis. Increasing PTS severity was associated with higher calf pump venous volume and higher ejection volume, leading to compensated calf pump performance. We found no evidence of PTS impact on exercise capacity. Leg contribution to power output was similar in affected and unaffected legs. However, the PTS-affected legs showed lower SmO2 during active cycling and recovery with increasing PTS severity, indicating impaired microvascular function in the muscle. These findings suggest that PTS severity is associated with impaired blood flow, presumably from elevated venous pressure during and after exercise. The fact that microvascular function is impaired in young patients with PTS underscores the relevance of developing strategies to mitigate the effects of this chronic vascular disease to minimize its deleterious effects as children grow older.

기왕력 유무에 따른 정맥혈류에 대한 종아리 펌프 운동의 효과 비교

Prolonged standing causes high blood pressure in the veins of the legs, contributing to damage to the valves of the veins, leading to chronic venous disease. This condition can be alleviated by activating the calf muscle pumps. This study was conducted to determine the effects of calf pump exercise on leg venous blood flow and to compare its effects in people with and without previous history of leg problem. Twenty-eight participants without a diagnosis of varicose veins and without limitations in ankle mobility were recruited for this study, and they were divided into two groups according to the presence or absence of a history of leg problems. The delay of blood flow was measured using ultrasonic images with a color Doppler, and the delay time was measured using the iPhone 11 camera application. Calf pump exercise was performed by lowering and raising heel while standing with 5 cm high wooden board touching the forefoot. There was found a significant difference in the delay time of blood flow between the groups with and without the history after the exercise (p<0.05). This finding suggests that calf pump exercises may help improve venous flow in the legs, especially in people with a history of leg problems.

Venous ulcers: look at the patient, not at the ulcer! Risk factors and comorbid conditions in venous ulcers of lower limbs.

In venous leg ulcers (VLU), risk factors and comorbidities may affect prognosis and recurrence. Aim of this paper was to assess risk factors and most frequent medical conditions in venous ulcers. This a single center retrospective study from January 2017 to December 2020 on 172 patients with VLU admitted at our Center for Ulcer therapy in San Filippo Neri Hospital in Rome; data about medical history, Duplex scanning results and lifestyle questionnaire were collected in an Excel database and evaluated with Fisher test. Patients with lower limbs arterial insufficiency were excluded. Incidence of VLU in patients over 65 was twice that in patients under 65 and woman were affected by VLU more than men (59.3% vs. 40.7%; P<0.001); more significant comorbidities were arterial hypertension in 44.19% (P=0.06), heart disease in 35.47% (P<0.001), chronic obstructive pulmonary disease (COPD) in 16.28% (P=0.008). In 33 patients (19% of cases) a trauma caused the ulcer. Diabetes, obesity, chronic renal insufficiency and orthopedic disease do not seem to have a direct influence on VLU. Age, female sex, arterial hypertension, heart disease and COPD were significant risk factors. Thinking "globally" to the patient rather than only taking the ulcer into account is the key for a long-lasting therapeutic result; comorbidities are interconnected so weight loss, an exercise program for calf pump and compression must all be part of the VLU therapy, not only to heal the existing ulcer but also to prevent recurrences.

Plethysmographic features of calf pump failure in chronic venous obstruction and reflux

Background Calf pump failure (CPF) is a common concept in chronic venous disease. Dorsal vein pressures were originally used to define the pathophysiology. More recently, an abnormal ejection fraction (EF) and residual volume fraction (RVF) with air plethysmography (APG) have been substituted for its diagnosis. The relationship between reflux and calf pump function has been studied extensively. Reflux is thought to be the main cause of CPF, although other mechanisms may play a secondary role. Data mining in our dataset revealed that CPF is frequently found in nonrefluxive limbs—an unexpected finding. We analyzed the APG features of CPF in nonrefluxive limbs of a large cohort of patients investigated for chronic venous disease in our clinic. Data from refluxive limbs (control) seen over the same period was included for comparison. Venous obstructive pathology was variably present in both subsets. Iliac vein stent outcome in CPF limbs from both subsets is included. The role of obstruction in CPF is currently unknown.

Diastolic compression device aimed at stopping refluxing flow

Theoretical concept of a diastolic compression device is presented. The device could have a form of a pneumatic cuff or a rubber sleeve. Its objective is to exert external pressure below the knee, which would compress the great saphenous vein during the diastolic phase of the calf pump activity, and hinder thereby the saphenous reflux and the occurrence of ambulatory venous hypertension. Based on the results of venous pressure measurements, it is supposed that pressure of about 35 mm Hg would be able to fulfill this therapeutic aim. If tolerated and accepted by the patients, the device could offer, in addition to the current invasive methods and compression stocking therapy, a simple conservative, nonetheless effective treatment of primary varicose veins. It would keep the dividing line of the ambulatory pressure gradient below the knee, as is the case with healthy people, and prevent thereby the progression of the disease. In addition, this conservative method would preserve the great saphenous vein for possible use as a bypass graft in the future.

Historical view onto the contribution of phlebodynamometry to the knowledge of venous hemodynamics in the lower extremity

Contribution of phlebodynamometry to the knowledge of the venous hemodynamics in the lower extremity is assessed from the historical point of view. Höjensgard, Stürup, and Arnoldi yielded in the 50's and 60's of the last century substantial information concerning changes of venous pressure in superficial and deep veins of the lower extremity arising during calf pump activity. They confirmed the previous finding that the venous pressure in the quiet standing position corresponds to the column of blood extending from the point of measurement to the heart. During calf pump activity, the systolic-diastolic amplitudes in lower leg veins are very marked; in contrast to that, they are only modest in the popliteal vein. The mentioned authors documented marked decrease in pressure in the posterior tibial vein as well as in the great saphenous vein arising during calf pump activity in healthy people. Contrary to that, the pressure in the popliteal vein did not decrease; it kept principally the value of the resting hydrostatic pressure. This difference of pressure between the thigh veins and the lower leg veins has been called ambulatory pressure gradient; its value in the examined patient cohort was 37.4±6.4 mm Hg. Ambulatory pressure gradient constitutes the suction force that triggers reflux in incompetent superficial and deep veins; this refluxing flow causes ambulatory venous hypertension. Simultaneous pressure recordings in the posterior tibial vein and great saphenous vein in healthy volunteers documented that the systolic and diastolic pressure amplitudes were similar in both veins. The systolic pressure in the posterior tibial vein increased on average by 75 mm Hg; this generates a strong impulse propelling the venous blood mainly into the popliteal vein, and partially into the great saphenous vein. Thus, there is a double-barreled outflow of venous blood from the lower extremity toward the heart. The steep increase in systolic pressure in the great saphenous vein gave evidence of the incompetence of the calf perforators system in healthy people. At present, plethysmography is able to yield similar information on the hemodynamic status of the lower limbs like phlebodynamometry.

Contribution of strain gauge plethysmography and photoplethysmography to the quantification of the hemodynamic disturbance in varicose vein disease

The significance of strain gauge plethysmography and photoplethysmography in the diagnostics of hemodynamic disturbance in primary varicose veins is discussed. Both methods have the ability to measure volume changes induced by calf pump activity and to quantify the pre-treatment hemodynamic disorders, the immediate post-treatment hemodynamic improvement, as well as the post-treatment deterioration occurring during the follow up. The most frequently used parameters are refill times t-90 and t-50; they yield precise and reliable results. For this reason, plethysmography is a rational supplement to duplex ultrasonography in the diagnostic investigation of varicose vein disease.

Retrospective Study on transfusion requirements and deep vein thrombosis incidence with the use of Tranexamic acid on total knee replacement

BACKGROUND Total knee replacement is often associated with significant blood loss and increased rate of blood transfusion. Tranexamic acid is a potent anti-fibrinolytic agent and its use in major surgeries has shown to decrease blood loss as well as transfusion rates. It is used intravenous, oral and topical forms as well. This study aims to find out the effectiveness of systemic Tranexamic acid in terms of decrease in transfusion rate as well incidence of deep vein thrombosis (DVT) and thromboembolism.&#x0D; MATERIALS AND METHODS Total number of patients were 94 of which 58 had bilateral knees replacement and 36 patient underwent unilateral knee replacement over the period of 3 years (December 2018 –December 2021). All patients were screened for general condition as well as any coagulopathy pre –op. All patients were given IV form of Tranexamic acid followed by oral form for 3 days post operatively. Tourniquet was used in all cases and low molecular weight heparin (Clexane) 40 mg subcutaneous once a day for 1-2 days followed by oral aspirin was given for 6 weeks to all patients. SCD calf pumps were used for 4 to 5 days.&#x0D; RESULTS We found that incidence of blood transfusion was only 6.9% in our case series which was well within the incidence reported in varied literature on the use of Tranexamic acid in knee replacement surgery. There was no clinical feature of deep vein thrombosis / pulmonary embolism (DVT/PE) in any of our patients.&#x0D; CONCLUSION Use of Tranexamic acid is a safe and effective method for controlling blood loss and decreasing the transfusion rate after total knee replacement surgery. Its intravenous and oral forms are readily available and cost effective. Its use is not associated with DVT or PE.

Assessing the Effectiveness of Lower Limb Home Exercises with the Use of a Prototype Exercise Robot for Continuous Passive Movement in People with Tetraparesis in the Long-Term Follow-Up: a Preliminary Report

Introduction: Chronic venous insufficiency is the most commonly occurring vascular disease. One of the major risk factors for its development is long-term sitting or standing in prolonged unchanged position and the nature performed work. Study aim: The aim of this study was to assess the effectiveness of lower limb home exercises limb with the use of the Bella Vena robot following disease onset causing tetraparesis in long-term observation. Materials and methods: A group of 15 patients (43.80 ± 14.97 years) was enrolled in the study. These patients had experienced whiplash injury causing total or partial inertia, with preserved mobility in the ankle joints. The total duration of the observation lasted 8 months (8 visits), during which the following parameters were assessed at the beginning and end of this period: pain intensity – according to the Visual Analogue Scale (VAS), level of saturation on the toe, pulse rate of the lower limb via Doppler ultrasound evaluation of reflux parameters. Result: Statistically significant improvement was achieved after home exercises within the following ranges - quality of pain intensity on VAS (p≤0.01), saturation at the level of the big toe (p≤0.05), Doppler ultrasound: reflux in the right femoral vein (p≤0.05), Doppler ultrasound: reflux in the left femoral vein (p≤0.05) Conclusion: Home exercises with using a prototype of the Bella Vena device showed a moderate effect on improving calf pump in the group of patients with quadriplegia in long-term observation.

Plethysmographic features of calf pump failure in chronic venous obstruction and reflux

BackgroundCalf pump failure (CPF) is a common concept in chronic venous disease. Dorsal vein pressures were originally used to define the pathophysiology. More recently, an abnormal ejection fraction (EF) and residual volume fraction (RVF) with air plethysmography (APG) have been substituted for its diagnosis. The relationship between reflux and calf pump function has been studied extensively. Reflux is thought to be the main cause of CPF, although other mechanisms may play a secondary role. Data mining in our dataset revealed that CPF is frequently found in nonrefluxive limbs—an unexpected finding. We analyzed the APG features of CPF in nonrefluxive limbs of a large cohort of patients investigated for chronic venous disease in our clinic. Data from refluxive limbs (control) seen over the same period was included for comparison. Venous obstructive pathology was variably present in both subsets. Iliac vein stent outcome in CPF limbs from both subsets is included. The role of obstruction in CPF is currently unknown. MethodsRecords of 13,234 limbs in 8813 patients evaluated for suspected chronic venous disease over a 22-year period were analyzed. Prestent and poststent data in 406 CPF limbs (129 nonrefluxive; 277 refluxive) that underwent iliac vein stenting to correct associated stenosis are included. This is a single-center retrospective analysis of prospectively collected data. Duplex and APG data were available for included limbs. A RVF of more than 50% was defined as CPF. A reflux time of greater than 1 second elicited with automated cuffs in the erect position was defined as reflux. ResultsThere were 7780 (59%) limbs with reflux and 5454 (41%) that were nonrefluxive. Supine venous pressure, an index of venous obstruction, was elevated in both subsets. The incidence of CPF was 25% in refluxive limbs and 16% in nonrefluxive limbs totaling 2790 limbs. Venous volume and venous filling index were significantly elevated (P = .0001) in refluxive limbs compared to nonrefluxive limbs. The EF was diminished (<50%) in all CPF limbs except in a small fraction (n = 427 [3%]). Stent correction of iliac vein stenosis corrected CPF, normalizing the RVF in both subsets. ConclusionsCPF frequently occurs in nonrefluxive limbs with incidence only slightly less than in refluxive limbs. An RVF of more than 50% seems to be a practical definition of a CPF; an EF of less than 50% is associated with a RVF of greater than 50% in 97% of analyzed limbs. Prospective identification of CPF in limbs with chronic venous disease may allow more detailed investigation of its cause (preload, afterload, neuromuscular pathology or joint immobility, etc) and direct more targeted treatment than currently practiced.

Counter pressure maneuvers for syncope prevention: A semi-systematic review and meta-analysis.

Physical counter pressure maneuvers (CPM) are movements that are recommended to delay or prevent syncope (fainting) by recruiting the skeletal muscle pump to augment cardiovascular control. However, these recommendations are largely based on theoretical benefit, with limited data evaluating the efficacy of CPM to prevent syncope in the real-world setting. We conducted a semi-systematic literature review and meta-analysis to assess CPM efficacy, identify literature gaps, and highlight future research needs. Articles were identified through a literature search (PubMed, April 2022) of peer-reviewed publications evaluating the use of counter pressure or other lower body maneuvers to prevent syncope. Two team members independently screened records for inclusion and extracted data. From 476 unique records identified by the search, 45 met inclusion criteria. Articles considered various syncopal conditions (vasovagal = 12, orthostatic hypotension = 8, postural orthostatic tachycardia syndrome = 1, familial dysautonomia = 2, spinal cord injury = 1, blood donation = 10, healthy controls = 11). Maneuvers assessed included hand gripping, leg fidgeting, stepping, tiptoeing, marching, calf raises, postural sway, tensing (upper, lower, whole body), leg crossing, squatting, “crash” position, and bending foreword. CPM were assessed in laboratory-based studies (N = 28), the community setting (N = 4), both laboratory and community settings (N = 3), and during blood donation (N = 10). CPM improved standing systolic blood pressure (+ 14.8 ± 0.6 mmHg, p < 0.001) and heart rate (+ 1.4 ± 0.5 bpm, p = 0.006), however, responses of total peripheral resistance, stroke volume, or cerebral blood flow were not widely documented. Most patients experienced symptom improvement following CPM use (laboratory: 60 ± 4%, community: 72 ± 9%). The most prominent barrier to employing CPM in daily living was the inability to recognize an impending faint. Patterns of postural sway may also recruit the skeletal muscle pump to enhance cardiovascular control, and its potential as a discrete, proactive CPM needs further evaluation. Physical CPM were successful in improving syncopal symptoms and producing cardiovascular responses that may bolster against syncope; however, practical limitations may restrict applicability for use in daily living.

A Novel Methodology for the Synchronous Collection and Multimodal Visualization of Continuous Neurocardiovascular and Neuromuscular Physiological Data in Adults with Long COVID.

Background: Reports suggest that adults with post-COVID-19 syndrome or long COVID may be affected by orthostatic intolerance syndromes, with autonomic nervous system dysfunction as a possible causal factor of neurocardiovascular instability (NCVI). Long COVID can also manifest as prolonged fatigue, which may be linked to neuromuscular function impairment (NMFI). The current clinical assessment for NCVI monitors neurocardiovascular performance upon the application of orthostatic stressors such as an active (i.e., self-induced) stand or a passive (tilt table) standing test. Lower limb muscle contractions may be important in orthostatic recovery via the skeletal muscle pump. In this study, adults with long COVID were assessed with a protocol that, in addition to the standard NCVI tests, incorporated simultaneous lower limb muscle monitoring for NMFI assessment. Methods: To conduct such an investigation, a wide range of continuous non-invasive biomedical sensing technologies were employed, including digital artery photoplethysmography for the extraction of cardiovascular signals, near-infrared spectroscopy for the extraction of regional tissue oxygenation in brain and muscle, and electromyography for assessment of timed muscle contractions in the lower limbs. Results: With the proposed methodology described and exemplified in this paper, we were able to collect relevant physiological data for the assessment of neurocardiovascular and neuromuscular functioning. We were also able to integrate signals from a variety of instruments in a synchronized fashion and visualize the interactions between different physiological signals during the combined NCVI/NMFI assessment. Multiple counts of evidence were collected, which can capture the dynamics between skeletal muscle contractions and neurocardiovascular responses. Conclusions: The proposed methodology can offer an overview of the functioning of the neurocardiovascular and neuromuscular systems in a combined NCVI/NMFI setup and is capable of conducting comparative studies with signals from multiple participants at any given time in the assessment. This could help clinicians and researchers generate and test hypotheses based on the multimodal inspection of raw data in long COVID and other cohorts.

Ca2+ leak through ryanodine receptor 1 regulates thermogenesis in resting skeletal muscle

Mammals rely on nonshivering thermogenesis (NST) from skeletal muscle so that cold temperatures can be tolerated. NST results from activity of the sarcoplasmic reticulum (SR) Ca2+ pump in skeletal muscle, but the mechanisms that regulate this activity are unknown. Here, we develop a single-fiber assay to investigate the role of Ca2+ leak through ryanodine receptor 1 (RyR1) to generate heat at the SR Ca2+ pump in resting muscle. By inhibiting a subpopulation of RyR1s in a single-fiber preparation via targeted delivery of ryanodine through transverse tubules, we achieve in-preparation isolation of RyR1 Ca2+ leak. This maneuver provided a critical increase in signal-to-noise of the SR-temperature-sensitive dye ER thermoyellow fluorescence signal from the fiber to allow detection of SR temperature changes as either RyR1 or SR Ca2+ pump activity was altered. We found that RyR1 Ca2+ leak raises cytosolic [Ca2+] in the local vicinity of the SR Ca2+ pump to amplify thermogenesis. Furthermore, gene-dose-dependent increases in RyR1 leak in RYR1 mutant mice result in progressive rises in leak-dependent heat, consistent with raised local [Ca2+] at the SR Ca2+ pump via RyR1 Ca2+ leak. We also show that basal RyR Ca2+ leak and the heat generated by the SR Ca2+ pump in the absence of RyR Ca2+ leak is greater in fibers from mice than from toads. The distinct function of RyRs and SR Ca2+ pump in endothermic mammals compared to ectothermic amphibians provides insights into the mechanisms by which mammalian skeletal muscle achieves thermogenesis at rest.

Effect of body mass index on initial presentation and outcomes after stenting for quality of life–impairing chronic iliofemoral venous obstruction

ObjectiveThe incidence of obesity has been increasing, with recent data indicating that the age-adjusted mean body mass index (BMI) is close to 30 kg/m2 in the United States. Prior studies have raised concerns for an increased incidence of chronic venous insufficiency in the obese population. We aimed to build on current knowledge by assessing the effects of BMI on the initial presentation and outcomes after intravascular ultrasound (IVUS) luminal area-guided stenting in patients presenting with quality of life (QOL)-impairing chronic iliofemoral venous obstruction (CIVO). MethodsA retrospective analysis of contemporaneously entered electronic medical record data on 464 continuous patients (464 limbs) with initial iliofemoral stents (2014-2017) for QOL-impairing CIVO was performed. The characteristics evaluated and compared included the degree of iliofemoral compression, CEAP (clinical, etiologic, anatomic, pathophysiologic) clinical class, venous clinical severity score (VCSS), grade of swelling (GOS), visual analog scale (VAS) for pain score, ulcer healing, reflux (venous segmental disease score; venous filling index-90), calf pump function (ejection fraction; residual volume fraction), and quality of life (CIVIQ-20 [chronic lower limb venous insufficiency 20-item questionnaire]) for those with a BMI <30 kg/m2 (group I) and a BMI ≥30 kg/m2 (group II). Paired and unpaired t tests were used for comparisons of the clinical variables and a Kaplan-Meier analysis was used to evaluate stent patency. ResultsOf the 464 limbs in the study cohort, 122 were in group I and 342 in group II. The median BMI was 26.3 kg/m2 (interquartile range, 19.6-29.9 kg/m2) in group I and 38.9 kg/m2 (interquartile range, 30.0-66.9 kg/m2) in group II. The IVUS luminal area–determined degree of compression was higher in group I than in group II across the common iliac, external iliac, and common femoral segments (P < .01). The supine foot venous and femoral venous pressures were higher in group II than in group I (P < .001). The ejection fraction was higher (57.4% vs 45.6%; P = .0008) and residual volume fraction was lower (27.5% vs 40.5%; P = .0008) in group II than in group I. Although the baseline VCSS and GOS were lower in group I than in group II (P < .05), no differences were found in the VAS for pain scores or ulcer prevalence. The median follow-up was 22 months. At 24 months after stenting, improvement was found in the VCSS, GOS, and VAS for pain score in both groups. The CIVIQ-20 QOL score had improved from 58.1 to 18.8 in group I (P = .0002) and from 60 to 37.5 in group II (P < .0001). At 5 years, primary patency was 70% in group I and 73% in group II (P = .6) and primary assisted patency was 100% in both groups (P = .99) without a significant difference in the reintervention rate (P = .5). ConclusionsObese patients with CIVO-impairing QOL have a lesser degree of iliofemoral venous stenosis, more severe venous hypertension, and better calf pump function than their nonobese counterparts. After stenting, no differences were found in the clinical, stent patency, or QOL-related outcomes between the two groups.