Lactate distribution in red blood cells and plasma after a high intensity running exercise in aerobically trained and untrained subjects

Introduction: To determine endurance capacity and to give specific training recommendations, blood lactate (LA) concentrations are frequently used in performance diagnostics. In blood, LA is stored in red blood cells (RBC) and in plasma. Higher LA uptake by RBC might lead to delayed muscle fatigue since RBC serve as a dilution space for LA and more LA can be taken up by plasma which is released from the working muscle. Therefore, the aim of this study was to investigate the distribution of lactate in plasma and RBC in aerobically well-trained athletes (AA) in comparison to an untrained control group (CG). Materials and Methods: 13 AA and 13 CG participated in this study and conducted a high intensive treadmill test consisting of 2x4 minutes of running at 95% of the maximal running velocity with an active break of 4 minutes. Venous blood was drawn before and after the test. LA was measured in whole blood, plasma and RBC. Further, the ratio (LARatio) was calculated using the following formula: LA of RBC / LA of plasma. Results: AA exhibit significantly higher values in VO2peak and maximum running velocity. After the running test, LA in whole blood, RBC and plasma is increased significantly in both groups. No interaction effect (group X time point) was observed in any parameter. Values of LARatio did not show any significant differences. Conclusion: This study showed that the LA distribution in RBC and plasma after a high intensity running test is very similar in well trained endurance athletes and in untrained control subjects. Hence, LA uptake by RBC cannot or only in part be seen as a contributor to aerobic athletic performance

Increase in Red Blood Cell-Nitric Oxide Synthase Dependent Nitric Oxide Production during Red Blood Cell Aging in Health and Disease: A Study on Age Dependent Changes of Rheologic and Enzymatic Properties in Red Blood Cells.

To investigate RBC-NOS dependent NO signaling during in vivo RBC aging in health and disease.RBC from fifteen healthy volunteers (HC) and four patients with type 2 diabetes mellitus (DM) were separated in seven subpopulations by Percoll density gradient centrifugation.The proportion of old RBC was significantly higher in DM compared to HC. In both groups, in vivo aging was marked by changes in RBC shape and decreased cell volume. RBC nitrite, as marker for NO, was higher in DM and increased in both HC and DM during aging. RBC deformability was lower in DM and significantly decreased in old compared to young RBC in both HC and DM. RBC-NOS Serine1177 phosphorylation, indicating enzyme activation, increased during aging in both HC and DM. Arginase I activity remained unchanged during aging in HC. In DM, arginase I activity was significantly higher in young RBC compared to HC but decreased during aging. In HC, concentration of L-arginine, the substrate of RBC-NOS and arginase I, significantly dropped from young to old RBC. In DM, L-arginine concentration was significantly higher in young RBC compared to HC and significantly decreased during aging. In blood from healthy subjects, RBC-NOS activation was additionally inhibited by N5-(1-iminoethyl)-L-Ornithine dihydrochloride which decreased RBC nitrite, and impaired RBC deformability of all but the oldest RBC subpopulation.This study first-time showed highest RBC-NOS activation and NO production in old RBC, possibly to counteract the negative impact of cell shrinkage on RBC deformability. This was even more pronounced in DM. It is further suggested that highly produced NO only insufficiently affects cell function of old RBC maybe because of isolated RBC-NOS in old RBC thus decreasing NO bioavailability. Thus, increasing NO availability may improve RBC function and may extend cell life span in old RBC

Nitrite concentration and maximum RBC deformability (EI_max) in RBC after L-NIO incubation in comparison to untreated RBC.

<p>(A) RBC nitrite concentration was decreased in all subpopulations by L-NIO. Data are presented as Mean ± Standard Error of MEAN (n = 10). (B) EI_<b>max</b> values significantly decreased in subpopulations of 1.064 g/ml to 1.068 g/ml after L-NIO incubation. No decrease was observed in old subpopulations (1.070 g/ml and 1.076+ g/ml). Data are presented as Mean ± Standard Deviation (n = 10).</p

Linear regression of RBC-NOS^Ser1177 immunostaining and RBC nitrite concentration in HC and DM.

<p>Calculation of R and R² (goodness of fit) revealed positive correlation of RBC-NOS^Ser1177 and RBC nitrite for both study groups.</p

Maximal RBC deformability (EI_max) and nitrite concentration in RBC of HC and DM during cell aging.

<p>(A) In RBC of HC, EI_<b>max</b> values increased from 1.064 g/ml to 1.065 g/ml (P < 0.001), remained constant to 1.068 g/ml and then decreased with increasing cell age. Oldest RBC (1.076+ g/ml) showed lowest EI_<b>max</b> (P < 0.001 compared to 1.072 g/ml). EI_<b>max</b> of middle aged RBC (1.065–1.068 g/ml) was significantly lower in DM compared to HC. EI_<b>max</b> of DM significantly decreased during aging. Data are presented as mean ± standard deviation of n = 15 (HC) and n = 4 (DM). (B) In HC, RBC nitrite concentration remained constant from 1.064 g/ml to 1.068 g/ml and then significantly increased reaching its maximum values at 1.076+ g/ml. RBC nitrite concentration was significantly higher in DM compared to HC for 1.064, 1.066, 1.0681.072 and 1.076+ g/ml. RBC nitrite concentration in RBC of DM increased during aging. Data are presented as mean ± standard deviation of n = 5 (HC) and n = 4 (DM).</p

Mean Cellular Volume (MCV) and phosphatidylserine (PS) externalisation with increasing cell age in HC and DM.

<p>(A) Mean cellular volume constantly decreased during aging in both groups. MCV of young and middle aged RBC was significantly decreased in DM compared to HC. RBC of HC lost 20% of MCV during aging (P < 0.001; comparison of old and young RBC). RBC of DM lost 12% of MCV during aging (P < 0.05; comparison of old and young RBC). Data are presented as mean ± standard deviation of n = 15 (HC) and n = 4 (DM). (B) In both groups, Annexin V, a marker for PS externalisation, significantly increased in the oldest subpopulation (P < 0.05 compared to 1.072 g/ml). Data are presented as mean ± standard deviation of n = 4 (HC) and n = 4 (DM).</p

RBC proportion of HC and DM in dependence of increased cell age.

<p>Bars show RBC proportion of fractionated subpopulations to total RBC volume, which were divided into young (1.064 g/ml), middle old (1.065–1.068 g/ml) and old (1.070–1.076+ g/ml) RBC. In both study groups, middle old RBC represented the main proportion on total RBC volume. DM showed significantly higher amount of old RBC compared to HC. Data are presented as mean ± standard deviation of n = 15 (HC) and n = 4 (DM).</p

Inflammation and severity of depressive symptoms in physically active individuals after COVID-19 – An exploratory immunopsychological study investigating the effect of inflammation on depressive symptom severity

Background: SARS-CoV-2 infection is a risk factor for the development of depressive symptoms such as lack of energy, loss of interest, and depressed mood. Inflammatory processes might underline this association. The aim of this study was to investigate the association between inflammatory markers and the severity of depression after SARS-CoV-2 infection and the predictive effect of inflammatory markers on the severity of depressive symptoms. Lifestyle factors and lifestyle-related diseases can influence inflammation and depressive symptoms. As these lifestyle factors and lifestyle-related diseases are less common in physically active individuals, they are a suitable population for investigating this research question. Methods: We investigated 61 at least moderate physically active individuals on average ∼6 months (SD = 4.22, range = 0.5–19 months) after SARS-CoV-2 infection (t0) and performed a follow-up after 3 months (t1). Depressive symptoms and biomarkers of inflammation (interleukin [IL]-1β, IL-8, IL-10, Ferritin, Lipopolysaccharide-binding-protein [LBP], neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR]) and kynurenine [KYN] were measured at both time points. Concentrations of inflammatory markers at t0 were used to predict the severity of depressive symptoms at t0 and t1. Results: Concentrations of KYN were negatively related to the severity of depressive symptoms at t0. Concentrations of LMR predicted higher depressive symptoms at t0 as well as at t1. Furthermore, individuals with lower concentrations of LBP at t0 showed a higher severity of depressive symptoms at t1. No correlation was found between severity of depressive symptoms and IL-1β, IL-8, IL-10, ferritin, NLR, and PLR at both time points. Conclusions: KYN, LBP and LMR might be useful as a predictive factor of depressive symptoms in physically active individuals after SARS-CoV-2 infection. While the results for KYN confirm the current scientific evidence, our results highlight the importance of the innovative inflammatory markers LMR and LBP. LMR and LBP might be interesting targets for predicting the development of depressive symptoms in SARS-CoV-2 infected populations and should be further investigated in future studies

Effect of acute exercise on RBC deformability and RBC nitric oxide synthase signalling pathway in young sickle cell anaemia patients

Sickle cell anaemia (SCA) is characterized by reduced red blood cell (RBC) deformability and nitric oxide (NO) bioavailability. The aim of the study was to investigate whether exercise might affect these parameters in SCA. SCA patients and healthy controls (AA) performed an acute submaximal exercise test until subjects reached the first ventilatory threshold (VT1). Blood was sampled at rest and at VT1. At rest, free haemoglobin level was higher and RBC count, haemoglobin and haematocrit were lower in SCA compared to AA. RBC deformability was lower in SCA. Exercise had no effect on the tested parameters. RBC NO level was higher in SCA compared to AA at rest and significantly decreased after exercise in SCA. This might be related to a reduction in RBC-NO synthase (RBC-NOS) activation which was only observed in SCA after exercise. Free radical levels were higher in SCA at rest but concentration was not affected by exercise. Marker for lipid peroxidation and antioxidative capacity were similar in SCA and AA and not affected by exercise. In conclusion, a single acute submaximal bout of exercise has no deleterious effects on RBC deformability or oxidative stress markers in SCA, and seems to modulate RBC-NOS signalling pathway