WISE 2005: chronic bed rest impairs microcirculatory endothelium in women

2007 ◽  
Vol 293 (5) ◽  
pp. H3159-H3164 ◽  
Author(s):  
Claire Demiot ◽  
Françoise Dignat-George ◽  
Jacques-Olivier Fortrat ◽  
Florence Sabatier ◽  
Claude Gharib ◽  
...  

Sedentary behavior has deleterious effects on the cardiovascular system, including reduced endothelial functions. A 2-mo bed rest study in healthy women [women international space simulation for exploration (WISE) 2005 program] presented a unique opportunity to analyze the specific effects of prolonged inactivity without other vascular risk factors on the endothelium. We investigated endothelial properties before and after 56 days of bed rest in 8 subjects who performed no exercise (control group: No-EX) and in 8 subjects who regularly performed treadmill exercise in a lower body negative pressure chamber as well as resistance exercise (countermeasure group, EX). A functional evaluation of the microcirculation in the skin was assessed with laser Doppler. We studied endothelium-dependent and -independent vasodilation using iontophoresis of acetylcholine and sodium nitroprusside, respectively. We also measured circulating endothelial cells (CECs), an index of endothelial damage. In the No-EX group, endothelium-dependent vasodilation was significantly reduced (35.4 ± 4.8% vs. 24.1 ± 3.8%, P < 0.05) by bed rest with a significant increase in the number of CECs (3.6 ± 1.4 vs. 10.6 ± 2.7 ml−1, P < 0.05). In the EX group, endothelium-dependent vasodilation and number of CECs were preserved. Our study shows that in humans prolonged bed rest causes impairment of endothelium-dependent function at the microcirculatory level, along with an increase in circulating endothelial cells. Microcirculatory endothelial dysfunction might participate in cardiovascular deconditioning, as well as in several bed rest-induced pathologies. We therefore conclude that the endothelium should be a target for countermeasures during periods of prolonged deconditioning.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 811.1-811
Author(s):  
S. Smiyan ◽  
A. Bilukha ◽  
B. Koshak

Background:Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which develops in patients with psoriasis. Mortality among patients with PsA is 1.28 times higher than population levels and in most cases it is caused by cardio-vascular diseases (CVD). Those patients have increased risk of clinical and subclinical CVD, mostly due to endothelial dysfunction (ED) and accelerated atherosclerosis. Elevated levels of circulating endothelial cells (CEC) have been described in different cardiovascular pathologies, suggesting their potential use as diagnostic biomarkers for dysfunction of endothelium.Objectives:To identify the potential role of circulating endothelial cells as a marker of cardiovascular diseases in patients with psoriatic arthritis.Methods:In total, ninety-four patients with PsA, who fulfilled the disease criteria (CASPAR) were examined using standard diagnostic methods (including C-reactive protein (CRP), lipid profile) and evaluation endothelium-dependent vasodilation in response to reactive hyperemia (EDVD). Circulating endothelial cells were determined in the peripheral venous blood samples by flow cytometry and counted according to a standardized protocol using a fluorescence microscope after acridine orange labeling. The control group, which were consisted from thirty healthy adults were also examined.Results:CEC were quantified in patients with PsA (7,15 ± 0,19 cells mL−1) and in the control group (4,05 ± 0,11 cells mL−1). Comparing two groups of patients, endothelial circulating cell level was significantly different (p = 0.0001). Finally, we analyzed the relationship between CEC count, comorbidities, cardiovascular risk factors and EDVD in patients with PsA. Increased CEC levels were associated with obesity (r=0,62), duration of disease (r=0,65), age (r=0,67), increased CRP (r=0,76), high blood pressure (r=0,87) and decreased EDVD (r=–0,91).Conclusion:CEC counts were significantly higher in patients with PsA, positively correlated with the main factors of CVD, and another specific marker of ED - EDVD. Elevated CEC levels were also associated with high concentrations of CRP, which plays a direct role in promoting vascular inflammation, vessel damage and clinical CVD events. In conclusion, increased CEC counts provide a direct proof of endothelial damage in patient with PsA and a clinically informative diagnostic tool for endothelial damage in pre-symptomatic CVD. As CEC are one of the most sensitive biomarker for ED, further efforts should concentrate on improving the sensitivity of its detection in order to increase diagnostic sensitivity.References:[1]Maura Farinacci, Thomas Krahn, Wilfried Dinh, et al. Circulating endothelial cells as biomarker for cardiovascular diseases. Res Pract Thromb Haemost, Vol. 3, Issue, 2019, P.49-58;[2]C. Horreau, C. Pouplard, E. Brenautet, et al. Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review. J Eur Acad Dermatol Venereol, Vol. 27, Issue 3, 2013, P.12-19;[3]Frank Verhoeven, Clément Prati, Céline Demougeot, Daniel Wendling. Cardiovascular risk in psoriatic arthritis, a narrative review. Joint Bone Spine, Vol. 87, Issue 5, 2020, P.413-418;Disclosure of Interests:None declared.


2016 ◽  
Vol 120 (10) ◽  
pp. 1215-1222 ◽  
Author(s):  
Jacquelyn A. Holt ◽  
Brandon R. Macias ◽  
Suzanne M. Schneider ◽  
Donald E. Watenpaugh ◽  
Stuart M. C. Lee ◽  
...  

Microgravity-induced lumbar paraspinal muscle deconditioning may contribute to back pain commonly experienced by astronauts and may increase the risk of postflight injury. We hypothesized that a combined resistive and aerobic exercise countermeasure protocol that included spinal loading would mitigate lumbar paraspinal muscle deconditioning during 60 days of bed rest in women. Sixteen women underwent 60-day, 6° head-down-tilt bed rest (BR) and were randomized into control and exercise groups. During bed rest the control group performed no exercise. The exercise group performed supine treadmill exercise within lower body negative pressure (LBNP) for 3-4 days/wk and flywheel resistive exercise for 2–3 days/wk. Paraspinal muscle cross-sectional area (CSA) was measured using a lumbar spine MRI sequence before and after BR. In addition, isokinetic spinal flexion and extension strengths were measured before and after BR. Data are presented as means ± SD. Total lumbar paraspinal muscle CSA decreased significantly more in controls (10.9 ± 3.4%) than in exercisers (4.3 ± 3.4%; P < 0.05). The erector spinae was the primary contributor (76%) to total lumbar paraspinal muscle loss. Moreover, exercise attenuated isokinetic spinal extension loss (−4.3 ± 4.5%), compared with controls (−16.6 ± 11.2%; P < 0.05). In conclusion, LBNP treadmill and flywheel resistive exercises during simulated microgravity mitigate decrements in lumbar paraspinal muscle structure and spine function. Therefore spaceflight exercise countermeasures that attempt to reproduce spinal loads experienced on Earth may mitigate spinal deconditioning during long-duration space travel.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 441.1-441
Author(s):  
F. Pignataro ◽  
L. Zorzino ◽  
W. Maglione ◽  
A. Minniti ◽  
G. Clericuzio ◽  
...  

Background:Endothelial damage and fibroproliferative vasculopathy of small vessels are pathological hallmarks of Systemic Sclerosis (SSc). Detection and analysis of circulating endothelial cells (CECs) detached from affected blood vessels may be an informative tool to study vascular dysfunction and could be considered a novel biomarker of scleroderma vasculopathy. Our group first showed the presence of CECs in SSc by fluorescence-activated cell sorting (FACS), demonstrating that a raised counts of active CECs may represent direct evidence of active vascular disease in SSc. Despite these interesting data, issues related to difficulties in CEC counting through FACS analysis, due their very low concentration in peripheral blood, prevented further investigations in this field. Recently, a specific kit for the detection of CECs has been developed through the CellSearch System (CS), a semi-automated device for the standardized analysis of rare cells, such as CECs, in peripheral blood.Objectives:To assess the counts of CECs determined by the CS in SSc patients and to evaluate their clinical implication and potential as vascular biomarker in SSc.Methods:10mL of blood samples were collected from 29 subjects (19 SSc patients and 10 healthy donors - HDs) and stored in tubes containing a specific preservative, to allow the analysis of 4mL of blood within 72 hours, according to manufacturer instructions. Out of 19 SSc patients, 18 were female, 10 had the limited form and 9 the diffuse cutaneous variant of SSc. CS uses a proprietary kit containing a ferrofluid-based reagent, that target CD146 to magnetically capture CECs, and the immunofluorescent reagents to stain the CECs, defined as CD146+, CD105-PE+, DAPI+ and CD45-APC-. Clinical, laboratoristic and demographic data were also collected.Results:The mean number of CECs in patients with SSc was significantly higher in comparison to HDs (554/4mL vs. 53.5/4 mL, p=0.0042). When analyzed according to disease subset, both lcSSc and dcSSc showed significantly increased levels of CECs in comparison with HDs (p=0.003 and p=0.005, respectively). No statistical difference was observed in the mean number of CECs in patients with lcSSc compared to those with dcSSc. Regarding vascular involvement, the CECs counts strictly correlated with the presence of digital ulcers (DUs) (p=0.0001) showing a median of 863cells/4mL for the SSc patients with DUs versus a median of 276.2/4mL for the SSc patients without DUs. No statistical correlation was found between CECs and serological autoantibody pattern, skin parameters, or joint and muscle involvement. Patients with active disease, according to the EUSTAR Activity Index, showed a higher CECs value than those with inactive disease (p=0.0012).Conclusion:The amount of CECs detectable in peripheral blood has been recently proposed as a marker of endothelial damage in different vascular diseases, including SSc. However, currently no standardized method is available to determine CEC counts, which makes reported data on CECs reliable and suitable. The CS system is a commercially available semi-automated system that enables standardized determination of CECs. Thus, we examined clinical utility of CECs count by this system in SSc patients. Our results confirm that baseline CEC counts, evaluated by a new standardized method, may represent direct evidence of endothelial damage in SSc and could be a promising tool for monitoring active disease and evaluating therapeutic responses to vascular and immunosuppressive treatments.References:[1]Del Papa N, Pignataro F. Front Immunol. 2018 Jun 18;9:1383[2]De Simone C et al. J Eur Acad Dermatol Venereol. 2014 May;28(5):590-6[3]Del Papa N et al. Arthritis Rheum. 2004 Apr;50(4):1296-304Disclosure of Interests:Francesca Pignataro: None declared, Laura Zorzino: None declared, Wanda Maglione: None declared, Antonina Minniti: None declared, Giulia Clericuzio: None declared, Marco Picozzi: None declared, Cecilia Simonelli Employee of: Menarini Silicon Biosystems, Francesco Picardo Employee of: Menarini Silicon Biosystems, Roberto Caporali: None declared, Nicoletta Del Papa: None declared


Author(s):  
T. Bulduk ◽  
A. U. Yalcin ◽  
O. M. Akay ◽  
S. G. Ozkurt ◽  
H. U. Teke ◽  
...  

Anemia is a common complication of chronic kidney disease (CKD). The most common cause of anemia in CKD is erythropoietin deficiency; and the most important cause of mortality in CKD patients is atherosclerotic vascular complications which are associated with endothelial damage. One of the methods evaluating vascular integrity is the cytometric measurement of circulating endothelial cells and endothelial progenitor cells in peripheral blood. The study aimed to investigate the effects of erythropoietin therapy on endothelial dysfunction by evaluating circulating endothelial cells and endothelial progenitor cells in peripheral blood using the technique of flow cytometry. Methods. A total of 55 hemodialysis patients were evaluated in three groups; those having erythropoietin therapy for at least last 3 months (n = 20) / not having erythropoietin for at least the last 3 months (n = 20) and the patients who started erythropoietin treatment during the study (n = 5). The control group consisted of 20 people. Blood values of the 3rd Group were investigated three times as baseline, 2nd week and 8th week CD34 +, CD105 + cells were evaluated as activated circulating endothelial cells; CD133 +, CD146 + cells were evaluated as activated endothelial progenitor cells. Results. There was no difference between the patients and healthy individuals in terms of circulating endothelial cells and endothelial progenitor cells. In the third group, no differences were observed in circulating endothelial cells / endothelial progenitor cell levels at baseline / 2nd and 8th weeks. There was no correlation between erythropoietin and circulating endothelial cells / endothelial progenitor cells. Conclusion. A correlation is not available between the therapeutic doses of erythropoietin used in hemodialysis patients and circulating endothelial cells / endothelial progenitor cell levels; supratherapeutic doses could change the results.


2020 ◽  
Author(s):  
VP Katuntsev ◽  
TV Sukhostavtseva ◽  
AN Kotov ◽  
MV Baranov

Reduced orthostatic tolerance (OT) is a serious concern facing space medicine. This work sought to evaluate the effects of intermittent hypoxic training (IHT) on OT in humans before and after 3 days of head-down bed rest (HDBR) used to model microgravity. The study was carried out in 16 male volunteers aged 18 to 40 years and included 2 series of experiments with 11-day and 21-day IHT administered on a daily basis. During the first IHT session, the concentration of oxygen in the inspired gas mixture was 10%; for other sessions it was adjusted to 9%. OT was assessed by a 20-minute-long orthostatic tilt test (OTT) conducted before and after HDBR. Before HDBR, orthostatic intolerance was observed in 3 participants, while after HDBR, it was observed in 9 of 16 volunteers (p < 0.05). During OTT conducted after HDBR, the heart rate (HR) exceeded control values by 26.8% (p < 0.01). Preexposure to any of the applied IHT regimens led to a reduction in the number of volunteers with orthostatic intolerance. After the 11-day IHT program, there was a less pronounced increase in HR during OTT before HDBR; with the extended IHT regimen, less pronounced changes were observed for HR, systolic, diastolic and mean blood pressure (BP). The increase in HR during OTT after HDBR was significantly lower in the group that had completed the 11-day IHT program, while BP remained stable. The changes in HR and systolic BP were less pronounced in the group that had completed the 21-day IHT program than in the control group (p < 0.05). Thus, IHT reduced the risk of orthostatic disorders and mitigated changes in cardiovascular parameters during the orthostatic test.


2002 ◽  
Vol 282 (6) ◽  
pp. H2210-H2215 ◽  
Author(s):  
Mazhar H. Khan ◽  
Allen R. Kunselman ◽  
Urs A. Leuenberger ◽  
William R. Davidson ◽  
Chester A. Ray ◽  
...  

Bed rest reduces orthostatic tolerance. Despite decades of study, the cause of this phenomenon remains unclear. In this report we examined hemodynamic and sympathetic nerve responses to graded lower body negative pressure (LBNP) before and after 24 h of bed rest. LBNP allows for baroreceptor disengagement in a graded fashion. We measured heart rate (HR), cardiac output (HR × stroke volume obtained by echo Doppler), and muscle sympathetic nerve activity (MSNA) during a progressive and graded LBNP paradigm. Negative pressure was increased by 10 mmHg every 3 min until presyncope or completion of −60 mmHg. After bed rest, LBNP tolerance was reduced in 11 of 13 subjects ( P < .023), HR was greater ( P< .002), cardiac output was unchanged, and the ability to augment MSNA at high levels of LBNP was reduced (rate of rise for 30- to 60-mmHg LBNP before bed rest 0.073 bursts · min−1 · mmHg−1; after bed rest 0.035 bursts · min−1 · mmHg−1; P < 0.016). These findings suggest that 24 h of bed rest reduces sympathetic nerve responses to LBNP.


2019 ◽  
Vol 142 (2) ◽  
pp. 113-119
Author(s):  
Martin Řádek ◽  
Eva Babuňková ◽  
Martin Špaček ◽  
Tomáš Kvasnička ◽  
Jan Kvasnička

Background/Aims: Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) have been described as markers of endothelial damage and dysfunction in several diseases, including deep venous thrombosis. Their role in patients with known thrombophilia has not yet been evaluated. Both EPCs and CECs represent extremely rare cell populations. Therefore, it is essential to use standardized methods for their identification and quantification. Methods: In this study, we used multicolor flow cytometry to analyze the number of EPCs and CECs in patients with thrombophilia with or without a history of thrombosis. Patients with hematological malignancies after high-dose chemotherapy and patients with acute myocardial infarction were used as positive controls. Results: EPC and CEC immunophenotypes were determined as CD45dim/–CD34+CD146+CD133+ and CD45dim/–CD34+CD146+CD133–, respectively. Increased levels of endothelial cells were observed in positive control groups. No significant changes in the number of EPCs or CECs were detected in patients with thrombophilia compared to healthy controls. Conclusion: Our optimized multicolor flow cytometry method allows unambiguous identification and quantification of endothelial cells in the peripheral blood. Our results support previous studies showing that elevated levels of CECs could serve as an indicator of endothelial injury or dysfunction. Normal levels of CECs or EPCs were found in patients with thrombophilia.


2009 ◽  
Vol 106 (3) ◽  
pp. 919-928 ◽  
Author(s):  
Stuart M. C. Lee ◽  
Suzanne M. Schneider ◽  
Wanda L. Boda ◽  
Donald E. Watenpaugh ◽  
Brandon R. Macias ◽  
...  

We have shown previously that treadmill exercise within lower body negative pressure (LBNPex) maintains upright exercise capacity (peak oxygen consumption, V̇o2peak) in men after 5, 15, and 30 days of bed rest (BR). We hypothesized that LBNPex protects treadmill V̇o2peak and sprint speed in women during a 30-day BR. Seven sets of female monozygous twins volunteered to participate. Within each twin set, one was randomly assigned to a control group (Con) and performed no countermeasures, and the other was assigned to an exercise group (Ex) and performed a 40-min interval (40–80% pre-BR V̇o2peak) LBNPex (51 ± 5 mmHg) protocol, plus 5 min of static LBNP, 6 days per week. Before and immediately after BR, subjects completed a 30.5-m sprint test and an upright graded treadmill test to volitional fatigue. These results in women were compared with previously reported reductions in V̇o2peak and sprint speed in male twins after BR. In women, sprint speed (−8 ± 2%) and V̇o2peak (−6 ± 2%) were not different after BR in the Ex group. In contrast, both sprint speed (−24 ± 5%) and V̇o2peak (−16 ± 3%) were significantly less after BR in the Con group. The effect of BR on sprint speed and V̇o2peak after BR was not different between women and men. We conclude that treadmill exercise within LBNP protects against BR-induced reductions in V̇o2peak and sprint speed in women and should prove effective during long-duration spaceflight.


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