Even patients with mild COVID-19 symptoms after SARS-CoV-2 infection show prolonged altered red blood cell morphology and rheological parameters.

Infection with the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the associated coronavirus disease-19 (COVID-19) might affect red blood cells (RBC); possibly altering oxygen supply. However, investigations of cell morphology and RBC rheological parameters during a mild disease course are lacking and thus, the aim of the study. Fifty individuals with mild COVID-19 disease process were tested after the acute phase of SARS-CoV-2 infection (37males/13 females), and the data were compared to n = 42 healthy controls (30 males/12 females). Analysis of venous blood samples, taken at rest, revealed a higher percentage of permanently elongated RBC and membrane extensions in COVID-19 patients. Haematological parameters and haemoglobin concentration, MCH and MCV in particular, were highly altered in COVID-19. RBC deformability and deformability under an osmotic gradient were significantly reduced in COVID-19 patients. Higher RBC-NOS activation was not capable to at least in part counteract these reductions. Impaired RBC deformability might also be related to morphological changes and/or increased oxidative state. RBC aggregation index remained unaffected. However, higher shear rates were necessary to balance the aggregation-disaggregation in COVID-19 patients which might be, among others, related to morphological changes. The data suggest prolonged modifications of the RBC system even during a mild COVID-19 disease course.

SARS-CoV-2 Altered Hemorheological and Hematological Parameters during One-Month Observation Period in Critically Ill COVID-19 Patients.

Hematological and hemorheological parameters are known to be altered in COVID-19; however, the value of combined monitoring in order to deduce disease severity is only scarcely examined. A total of 44 acute SARS-CoV-2-infected patients (aCOV) and 44 age-matched healthy controls (Con) were included. Blood of aCOV was sampled at admission (T0), and at day 2 (T2), day 5 (T5), day 10 (T10), and day 30 (T30) while blood of Con was only sampled once. Inter- and intra-group differences were calculated for hematological and hemorheological parameters. Except for mean cellular volume and mean cellular hemoglobin, all blood cell parameters were significantly different between aCOV and Con. During the acute disease state (T0-T5), hematological and hemorheological parameters were highly altered in aCOV; in particular, anemic conditions and increased immune cell response/inflammation, oxidative/nitrosative stress, decreased deformability, as well as increased aggregation, were observed. During treatment and convalescence until T30, almost all abnormal values of aCOV improved towards Con values. During the acute state of the COVID-19 disease, the hematological, as well as the hemorheological system, show fast and potentially pathological changes that might contribute to the progression of the disease, but changes appear to be largely reversible after four weeks. Measuring RBC deformability and aggregation, as well as oxidative stress induction, may be helpful in monitoring critically ill COVID-19 patients.

Proteinuric chronic kidney disease is associated with altered red blood cell lifespan, deformability and metabolism.

Anemia is a common complication of chronic kidney disease, affecting the quality of life of patients. Among various factors, such as iron and erythropoietin deficiency, reduced red blood cell (RBC) lifespan has been implicated in the pathogenesis of anemia. However, mechanistic data on in vivo RBC dysfunction in kidney disease are lacking. Herein, we describe the development of chronic kidney disease-associated anemia in mice with proteinuric kidney disease resulting from either administration of doxorubicin or an inducible podocin deficiency. In both experimental models, anemia manifested at day 10 and progressed at day 30 despite increased circulating erythropoietin levels and erythropoiesis in the bone marrow and spleen. Circulating RBCs in both mouse models displayed altered morphology and diminished osmotic-sensitive deformability together with increased phosphatidylserine externalization on the outer plasma membrane, a hallmark of RBC death. Fluorescence-labelling of RBCs at day 20 of mice with doxorubicin-induced kidney disease revealed premature clearance from the circulation. Metabolomic analyses of RBCs from both mouse models demonstrated temporal changes in redox recycling pathways and Lands' cycle, a membrane lipid remodeling process. Anemic patients with proteinuric kidney disease had an increased proportion of circulating phosphatidylserine-positive RBCs. Thus, our observations suggest that reduced RBC lifespan, mediated by altered RBC metabolism, reduced RBC deformability, and enhanced cell death contribute to the development of anemia in proteinuric kidney disease.

Brachial and central blood pressure and arterial stiffness in adult elite athletes.

PURPOSE: Measures of arterial stiffness (AS) and central blood pressure (BP) are indicators for cardiovascular health and possess a high prognostic value in the prediction of cardiovascular events. The effects of physical training are widely unexplored in the context of competitive, high-performance sports. Therefore, we aimed to present possible reference values of brachial and central BP and of AS of adult elite athletes compared to a control group. METHODS: A total of 189 subjects participated in this cross-sectional study. Of these were 139 adult elite athletes (70 male, 69 female) performing on top-national and international level, and 50 control subjects (26 male, 24 female). Resting brachial and central BP and aortic pulse wave velocity (PWV) were measured and were compared in terms of sex, sport category, and age of the athletes. RESULTS: Results show no difference between athletes and controls in any parameter. Women exhibit lower brachial and central BP and AS values compared to men. PWV is positively correlated with age. Evaluation of the parameters according to the different sport categories showed that endurance athletes exhibit lower BP and PWV compared to other athletes. CONCLUSIONS: This study presents brachial and central BP and PWV values of athletes, suggesting that high-performance sport does not negatively impact AS. The proposed reference values might support a more detailed evaluation of elite athlete's cardiovascular and hemodynamic system and a better assignment to possible risk groups.

Thrombospondin-1/CD47 signaling modulates transmembrane cation conductance, survival, and deformability of human red blood cells.

BACKGROUND: Thrombospondin-1 (TSP-1), a Ca2+-binding trimeric glycoprotein secreted by multiple cell types, has been implicated in the pathophysiology of several clinical conditions. Signaling involving TSP-1, through its cognate receptor CD47, orchestrates a wide array of cellular functions including cytoskeletal organization, migration, cell-cell interaction, cell proliferation, autophagy, and apoptosis. In the present study, we investigated the impact of TSP-1/CD47 signaling on Ca2+ dynamics, survival, and deformability of human red blood cells (RBCs). METHODS: Whole-cell patch-clamp was employed to examine transmembrane cation conductance. RBC intracellular Ca2+ levels and multiple indices of RBC cell death were determined using cytofluorometry analysis. RBC morphology and microvesiculation were examined using imaging flow cytometry. RBC deformability was measured using laser-assisted optical rotational cell analyzer. RESULTS: Exposure of RBCs to recombinant human TSP-1 significantly increased RBC intracellular Ca2+ levels. As judged by electrophysiology experiments, TSP-1 treatment elicited an amiloride-sensitive inward current alluding to a possible Ca2+ influx via non-selective cation channels. Exogenous TSP-1 promoted microparticle shedding as well as enhancing Ca2+- and nitric oxide-mediated RBC cell death. Monoclonal (mouse IgG1) antibody-mediated CD47 ligation using 1F7 recapitulated the cell death-inducing effects of TSP-1. Furthermore, TSP-1 treatment altered RBC cell shape and stiffness (maximum elongation index). CONCLUSIONS: Taken together, our data unravel a new role for TSP-1/CD47 signaling in mediating Ca2+ influx into RBCs, a mechanism potentially contributing to their dysfunction in a variety of systemic diseases. Video abstract.

Effects of a highly intensive clean and jerk exercise on blood pressure and arterial stiffness in experienced non-professional weight lifters.

PURPOSE: Weight lifting training has gained much popularity in recent years and is frequently used in non-professional and professional settings. However, little is known about the acute effects of a highly intensive weight lifting exercise (clean and jerk) on the hemodynamic reaction. METHODS: 18 non-professional experienced weight lifters were recruited. Hemodynamic parameters were obtained and measured at baseline (T1), after warming up (T2), and after a highly intensive clean and jerk exercise (90-95% of personal best; T3). Further, 15 (T4), and 30 min (T5) post-exercise measurements were conducted. Evaluated parameters were heart rate (HR) (b/min), peripheral and central systolic and diastolic blood pressure (pSysBP, pDiaBP, cSysBP, cDiaBP) (mmHg), pulse wave velocity (PWV) (m/s), and double product (DP). RESULTS: All hemodynamic values increased from T1 up to T3 with significantly higher values measured at T3 compared to T1 and T2. Values of measured parameters at T3 were as follows: HR: 94.4 ± 15.6 b/min, pSysBP: 147.1 ± 15.9 mmHg, pDiaBP: 87.4 ± 12.2 mmHg, cSysBP: 129.3 ± 13.8 mmHg, cDiaBP: 89.9 ± 12.8 mmHg, and: 5.8 ± 0.5 m/s, DP: 14053 ± 3669. Post-exercise (T4, T5), all values returned to baseline levels. CONCLUSIONS: Results indicate that a highly intensive weight lifting exercise led to an acute increase of blood pressure and an acute stiffening of the arteries. Yet, increases were moderate and did not reach disproportionately high levels and returned to baseline levels within 15 min post-exercise. Hence, no negative acute effects of a maximum weight lifting exercise on the hemodynamic system are observed.

Acute alterations in the hematological and hemorheological profile induced by resistance training and possible implication for microvascular functionality.

Depending on the exercise variables and training design, resistance exercise can be applied to gain muscle mass, prevent diseases like osteoporosis and sarcopenia or generally increase strength capacity. But the influence on blood flow parameters and possible consequences in health and disease are less understood. To examine the possible impact of resistance exercise of different duration on hemorheology, oxidative stress and microvascular function, participants (n = 6) performed lower-limb resistance exercise of the quadriceps femoris. Loading consisted of 1 (S1), 5 (S5) and 10 (S10) sets, on separated days, at the individual 10 repetition maximum. Blood samples were taken before (Pre) and after (Post0) each set as well after a 25-min recovery period (Post25). Hemograms were measured to analyze hematocrit, white blood cell (WBC) count and red blood cell (RBC) count. RBC deformability and aggregation were measured by ektacytometry and syllectometry to determine hemorheological responses. Plasma and RBC nitrate were measured by chemiluminescence detection to determine nitric oxide production. Formation of N-tyrosine and plasma malondialdehyde to determine oxidative stress and lipid peroxidation were measured by immunostaining and ELISA, respectively. Hematocrit, RBC, WBC count and aggregation increased Post0 in each protocol with subsequently decreased values Post25 below Pre values. High effect size was observed regarding deformability during the different sets. RBC nitrite analysis revealed effect size alterations between the trainings, whereas plasma nitrite was not affected. Effects size was evident in lipid peroxidation, whereas N-tyrosine concentration was not altered. Lower-limb resistance exercise induced acute changes in hematological and hemorheological parameters, whereby intermittent hemodilution and plasma shifts seemed the major contributor. The acute adaptations of RBC function seen during short duration resistance exercise might contribute to beneficial effects on microvascular circulation with a low oxidative stress response.

Hydroxyurea therapy modulates sickle cell anemia red blood cell physiology: Impact on RBC deformability, oxidative stress, nitrite levels and nitric oxide synthase signalling pathway.

Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU+ than in HU- and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU- than in HU+. RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation were decreased in HU+ compared to HU- and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal hemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.

Cryopreservation of red blood cells: Effect on rheologic properties and associated metabolic and nitric oxide related parameters.

AIM: High glycerol cryopreservation of red blood cells (RBCs) reduces metabolic processes at ultralow temperatures but less is known regarding the effect of cryopreservation on RBC nitric oxide (NO) metabolism, haemorheological properties, structural behaviour and membrane fragility. METHODS: Blood from ten healthy participants was sampled, glycerolized and stored at -80 °C (SB). Aliquots were thawed and further processed after 4, 8 and 12 weeks, respectively. At these time points, fresh blood (FB) was additionally sampled from each participant. FB/SB mixtures were prepared corresponding to transfusion of 1-3 blood bags. Additionally, mixtures were exposed to shear stress similar to that found in the circulation and deformability was measured to estimate possible behaviour of cryopreserved RBC in vivo. RESULTS: Ageing of RBC was reduced during cryopreservation. Markers for RBC metabolism (ATP, 2,3-DPG) were not altered but RBC sodium levels increased and potassium and calcium decreased, respectively. Mean cellular volume was higher and accordingly, mean cellular haemoglobin concentration was lower in SB. Deformability was altered during storage with less shear stress necessary to deform RBCs. Changes were also detectable in blood mixtures. Deformability remained unaltered in shear stress settings in FB and SB. RBC viscosity was reduced in SB. RBC-NOS content and phosphorylation sites as well as nitrite and RxNO levels seem not to be affected by the intervention. CONCLUSION: Cryopreservation maintains RBC metabolic function in vitro, but structure and function of cryopreserved RBC seems to be altered. Impact of these alterations in vivo seems to be less but needs further investigation.

Impact of Type of Sport, Gender and Age on Red Blood Cell Deformability of Elite Athletes.

Our objective was to detect possible differences in red blood cell (RBC) deformability of elite athletes performing different types of sports and being of different age and gender.182 athletes were included in this cross-sectional study. RBC deformability was measured using the laser-assisted optical rotational cell-analyzer. Maximal elongation index (EI max) and shear stress at half-maximum deformation (SS 1/2) were calculated. The ratio SS 1/2 /EI max (EI Ratio) was calculated with low values representing high RBC deformation. Hematocrit (Hct) and mean cellular volume (MCV) were determined in venous blood. Overall RBC deformability did not differ between male and female athletes but, when separated by age of the subjects, RBC deformability increased with age in male but not in female athletes. RBC deformability was lower in Combat sports compared other sport groups. Hct was higher in male compared to female athletes while no difference was observed for MCV. MCV and Hct increased with increasing age. A negative correlation was found between the EI Ratio and MCV and between EI Ratio and Hct. CONCLUSION: RBC deformability is influenced by age and endurance rate of the sport which suggests that the RBC system may adapt to changing conditions such as adolescence with the onset effects of sex hormones or physical exercise.

Ischemic Preconditioning Enhances Performance and Erythrocyte Deformability of Responders.

This pilot study aimed to evaluate the differential effects of a remote ischemic preconditioning (rIPC) manoeuvre on performance and red blood cell (RBC) deformability compared to a sham control and a placebo setting. Ten male subjects performed three test settings in a single-blind, crossover, and randomized control design. All settings started with 20 min of rest and were followed by 4 cycles of occlusion/reperfusion consisting of 5 min each. During rIPC and placebo, the cuff pressure was inflated to 200 mmHg and 120 mmHg, respectively. During the sham control setting, 10 mmHg pressure was applied. All tests were followed by a cycle exercise with lactate diagnostics. Power at 2 and 4 mmol/l lactate thresholds were calculated. RBC deformability was measured before and after the respective manoeuvre. Results showed that no effect resulted from any manoeuvre on performance values or RBC deformability. But 6 subjects showed a higher power at the 2 mmol/l threshold, and 5 subjects exerted higher power at the 4 mmol/l threshold when the rIPC manoeuvre preceded the exercise. In these responsive subjects, RBC deformability also improved. Hence, rIPC effects are much influenced by the subjects' responsiveness, and improved RBC deformability might contribute to enhanced performance in responsive subjects.

Effects of a Whole-Body Electrostimulation Program on Strength, Sprinting, Jumping, and Kicking Capacity in Elite Soccer Players.

The aim of the present study was to investigate the effect of a 14-week dynamic Whole-Body Electrostimulation (WB-EMS) training program on muscular strength, soccer relevant sprint, jump and kicking velocity performance in elite soccer players during competitive season. Twenty-two field-players were assigned to 2 groups: WB-EMS group (EG, n = 12), jump-training group (TG, n = 10). The training programs were conducted twice a week concurrent to 6-7 soccer training sessions during the 2nd half of the season. Participants were tested before (baseline), during (wk-7) and after (wk-14). Blood serum samples for analyzing IGF-1 and CK were taken before each testing, 15-30min post and 24h post the training program. Our findings of the present study were that a 14-week in-season WB-EMS program significant increased one-leg maximal strength (1RM) at the leg press machine (1.99 vs. 1.66 kg/kg, p = 0.001), and improved linear sprinting (5m: 1.01 vs. 1.04s, p=0.039), sprinting with direction changes (3.07 vs. 3.25s, p = 0.024), and vertical jumping performance (SJ: 38.8 vs. 35.9cm p = 0.021) as well as kicking velocity (1step: 93.8 vs. 83.9 km·h-1, p < 0.001). The TG showed no changes in strength and performance. The EG revealed significantly increased CK levels 24h post training and yielded significantly higher CK levels compared to the TG. IGF-1 serum levels neither changed in the EG nor in the TG. The results give first hints that two sessions of a dynamic WB-EMS training in addition to 6-7 soccer sessions per week can be effective for significantly enhancing soccer relevant performance capacities in professional players during competitive season.

High red blood cell nitric oxide synthase activation is not associated with improved vascular function and red blood cell deformability in sickle cell anaemia.

Human red blood cells (RBC) express an active and functional endothelial-like nitric oxide (NO) synthase (RBC-NOS). We report studies on RBC-NOS activity in sickle cell anaemia (SCA), a genetic disease characterized by decreased RBC deformability and vascular dysfunction. Total RBC-NOS content was not significantly different in SCA patients compared to healthy controls; however, using phosphorylated RBC-NOS-Ser(1177) as a marker, RBC-NOS activation was higher in SCA patients as a consequence of the greater activation of Akt (phosphorylated Akt-Ser(473) ). The higher RBC-NOS activation in SCA led to higher levels of S-nitrosylated α- and ß-spectrins, and greater RBC nitrite and nitrotyrosine levels compared to healthy controls. Plasma nitrite content was not different between the two groups. Laser Doppler flowmetric experiments demonstrated blunted microcirculatory NO-dependent response under hyperthermia in SCA patients. RBC deformability, measured by ektacytometry, was reduced in SCA in contrast to healthy individuals, and pre-shearing RBC in vitro did not improve deformability despite an increase of RBC-NOS activation. RBC-NOS activation is high in freshly drawn blood from SCA patients, resulting in high amounts of NO produced by RBC. However, this does not result in improved RBC deformability and vascular function: higher RBC-NO is not sufficient to counterbalance the enhanced oxidative stress in SCA.

Influence of Whole-Body Electrostimulation on Human Red Blood Cell Deformability.

Red blood cell-nitric oxide synthase (RBC-NOS)-dependent NO production is essential for the maintenance of RBC deformability, which is known to improve oxygen supply to the working tissue. Electrostimulation of the whole body (WB-EMS) has been shown to improve maximal strength, springiness, and jumping power of trained and untrained athletes. To examine whether these 2 parameters are associated, this study, for the first time, aimed to investigate the effects of an 18-week dynamic WB-EMS program on RBC deformability in addition to maximal strength performance (1 repetition maximum [1RM]) in elite soccer players. Fifteen test persons were assigned in either WB-EMS group (EG, n = 10) or training group (TG, n = 5). Next to their weekly training sessions, EG performed 3 × 10 squat jumps under the influence of WB-EMS twice per week between weeks 1 and 14 and once per week between weeks 14 and 18. Training group only performed 3 × 10 squat jumps. Performance was assessed by a maximal strength test on the leg press machine (1RM). Subjects were tested at baseline and after weeks 7, 14, and 18 with blood sampling before (Pre), 15-30 minutes after (Post), and 24 hours after (24-hour Post) the training. The results showed that maximal strength was significantly improved in EG (p < 0.01). Maximum RBC deformability (EImax) increased on EMS stimulus in EG while it remained unaffected in the TG. Acute increase in EImax at baseline was explained by an increase in RBC-NOS activation while chronic increase of deformability must be caused by different, yet unknown, mechanisms. EImax decreased between weeks 14 and 18 suggesting that 1 WB-EMS session per week is not sufficient to alter deformability (EImax). In contrast, the deformability at low shear stress (EI 3 Pa), comparable with conditions found in the microcirculation, significantly increased in EG until week 14, whereas in TG deformability only, increased until week 7 due to increasing training volume after the winter break. The results indicate that WB-EMS represents a useful and time-saving addition to conventional training sessions to improve RBC deformability and possibly oxygen supply to the working tissue and thus promoting general force components in high performance sport.

Skeletal muscle function during exercise-fine-tuning of diverse subsystems by nitric oxide.

Skeletal muscle is responsible for altered acute and chronic workload as induced by exercise. Skeletal muscle adaptations range from immediate change of contractility to structural adaptation to adjust the demanded performance capacities. These processes are regulated by mechanically and metabolically induced signaling pathways, which are more or less involved in all of these regulations. Nitric oxide is one of the central signaling molecules involved in functional and structural adaption in different cell types. It is mainly produced by nitric oxide synthases (NOS) and by non-enzymatic pathways also in skeletal muscle. The relevance of a NOS-dependent NO signaling in skeletal muscle is underlined by the differential subcellular expression of NOS1, NOS2, and NOS3, and the alteration of NO production provoked by changes of workload. In skeletal muscle, a variety of highly relevant tasks to maintain skeletal muscle integrity and proper signaling mechanisms during adaptation processes towards mechanical and metabolic stimulations are taken over by NO signaling. The NO signaling can be mediated by cGMP-dependent and -independent signaling, such as S-nitrosylation-dependent modulation of effector molecules involved in contractile and metabolic adaptation to exercise. In this review, we describe the most recent findings of NO signaling in skeletal muscle with a special emphasis on exercise conditions. However, to gain a more detailed understanding of the complex role of NO signaling for functional adaptation of skeletal muscle (during exercise), additional sophisticated studies are needed to provide deeper insights into NO-mediated signaling and the role of non-enzymatic-derived NO in skeletal muscle physiology.

Immunostaining-Based Detection of Dynamic Alterations in Red Blood Cell Proteins.

Antibody labeling of red blood cell (RBC) proteins is a commonly used, semi-quantitative method to detect changes in overall protein content or acute alterations in protein activation states. It facilitates the assessment of RBC treatments, characterization of differences in certain disease states, and description of cellular coherencies. The detection of acutely altered protein activation (e.g., through mechanotransduction) requires adequate sample preparation to preserve otherwise temporary protein modifications. The basic principle includes immobilizing the target binding sites of the desired RBC proteins to enable the initial binding of specific primary antibodies. The sample is further processed to guarantee optimal conditions for the binding of the secondary antibody to the corresponding primary antibody. The selection of non-fluorescent secondary antibodies requires additional treatment, including biotin-avidin coupling and the application of 3,3-diaminobenzidine-tetrahydrochloride (DAB) to develop the staining, which needs to be controlled in real-time under a microscope in order to stop the oxidation, and thus staining intensity, on time. For staining intensity detection, images are taken using a standard light microscope. In a modification of this protocol, a fluorescein-conjugated secondary antibody can be applied instead, which has the advantage that no further development step is necessary. This procedure, however, requires a fluorescence objective attached to a microscope for staining detection. Given the semi-quantitative nature of these methods, it is imperative to provide several control stains to account for non-specific antibody reactions and background signals. Here, we present both staining protocols and the corresponding analytical processes to compare and discuss the respective results and advantages of the different staining techniques.

Changes in Hematological and Hemorheological Parameters Following Mild COVID-19: A 4-Month Follow-Up Study.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) was described to affect red blood cells (RBC) in both severe and mild disease courses. The aim of this study was to investigate whether hematological and hemorheological changes that were previously described for COVID-19 patients after the acute infection state are still prominent after another 4 months to assess potential long-term effects. METHODS: Hematological and RBC rheological parameters, including deformability and aggregation, were measured 41 days after infection in COVID-19 patients and non-COVID control (T0) and 4 months later in COVID-19 patients (T1). RESULTS: The data confirm alterations in hematological parameters, mainly related to cell volume and hemoglobin concentration, but also reduced deformability and increased aggregation at T0 compared to control. While RBC deformability seems to have recovered, hemoglobin-related parameters and RBC aggregation were still impaired at T1. The changes were thus more pronounced in male COVID-19 patients. CONCLUSION: COVID-19-related changes of the RBC partly consist of several months and might be related to persistent symptoms reported by many COVID-19 patients.

Effects of Recurring IPC vs. rIPC Maneuvers on Exercise Performance, Pulse Wave Velocity, and Red Blood Cell Deformability: Special Consideration of Reflow Varieties.

Beneficial effects of (remote) ischemia preconditioning ((r)IPC), short episodes of blood occlusion and reperfusion, are well-characterized, but there is no consensus regarding the effectiveness of (r)IPC on exercise performance. Additionally, direct comparisons of IPC and rIPC but also differences between reflow modes, low reflow (LR) and high reflow (HR) in particular, are lacking, which were thus the aims of this study. Thirty healthy males conducted a performance test before and after five consecutive days with either IPC or rIPC maneuvers (n = 15 per group). This procedure was repeated after a two-week wash-out phase to test for both reflow conditions in random order. Results revealed improved exercise parameters in the IPC LR and to a lesser extent in the rIPC LR intervention. RBC deformability increased during both rIPC LR and IPC LR, respectively. Pulse wave velocity (PWV) and blood pressures remained unaltered. In general, deformability and PWV positively correlated with performance parameters. In conclusion, occlusion of small areas seems insufficient to affect large remote muscle groups. The reflow condition might influence the effectiveness of the (r)IPC intervention, which might in part explain the inconsistent findings of previous investigations. Future studies should now focus on the underlying mechanisms to explain this finding.

Influence of 24 h Simulated Altitude on Red Blood Cell Deformability and Hematological Parameters in Patients with Fontan Circulation.

Patients with Fontan circulation are particularly dependent on low pulmonary vascular resistance because their lungs are passively perfused. Hypoxia drives pulmonary vasoconstriction; thus, red blood cell (RBC) deformability and stability of hematological parameters might be of particular importance, because alterations during hypoxia might further influence circulation. This study aimed to measure respective parameters in patients with Fontan circulation exposed to normobaric hypoxia. A total of 18 patients with Fontan circulation (16 to 38 years) were exposed to normobaric hypoxia (15.2% ambient oxygen). Blood samples were taken in normoxia, after 24 h in hypoxia, and 60 min after return to normoxia. Blood count, RBC age distribution, EPO, RBC deformability, marker of RBC nitric oxide, oxidative state, and RBC ATP were measured. Hypoxia increased oxidative stress in RBC, but without affecting RBC deformability. RBC age distribution remained unaffected, although EPO concentrations increased, followed by a rise in reticulocyte count at an already high hematocrit. NO metabolism was not affected by hypoxia. Modest normobaric hypoxia for 24 h did not impair RBC deformability in patients with Fontan circulation; however, the oxidative system seemed to be stressed. Given the high baseline Hct in these patients, hypoxia-induced erythropoiesis could adversely affect rheology with more prolonged hypoxia exposure.