Early adulthood exercise capacity, but not muscle strength, associates with subclinical atherosclerosis 40 years later in Swedish men.

AIMS: Poor exercise capacity and muscle strength in early adulthood are risk factors for cardiovascular disease (CVD). However, it is unclear how these factors relate to subclinical atherosclerosis due to a lack of longitudinal studies. This study investigated whether early adulthood exercise capacity and muscle strength associated with later adulthood subclinical atherosclerosis. METHODS AND RESULTS: This study included Swedish men (n = 797) who were eligible for military conscription (at ∼18-years of age) and who participated in the baseline assessment of the visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention trial between 2013 and 2016 (at 60 years of age). At conscription, isometric muscle strength (dynamometer) and maximum exercise capacity (maximal load cycle ergometer test) were measured. During later adulthood (at 60 years old), the presence of carotid plaques and intima media thickness were measured by using high-resolution ultrasound. At follow-up, plaques were present in 62% (n = 493) of men. Exercise capacity in early adulthood associated with 19% lower odds of plaques [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.68-0.96], independent of muscle strength. This association was not mediated by any single CVD risk factor. However, the total indirect effect of later, but not early, adulthood CVD risk factors was significant, while the direct effect was non-significant (OR 0.85, 95% CI 0.71-1.02). Associations between muscle strength and subclinical atherosclerosis were non-significant. CONCLUSION: Higher exercise capacity during early adulthood, but not muscle strength, may protect against carotid plaque development during adulthood mediated by the combination rather than a single later adulthood CVD risk factors.

Swedish men who had high fitness at ∼18 years of age (early adulthood) had a lower prevalence of atherosclerotic plaques 40 years later (later adulthood), independent of muscle strength. The underlying mechanism of this protective association of higher fitness on the presence of plaques may be through the combination of later adulthood body mass index, systolic blood pressure, glucose tolerance status, non-HDL cholesterol, and triglycerides instead of through any single risk factor.Muscle strength during early adulthood was not associated with atherosclerosis during later adulthood.

Feasibility of an Online Delivered, Home-Based Resistance Training Program for Older Adults - A Mixed Methods Approach.

Background: Physical inactivity and low muscle mass are risk factors for falls, fractures and overall poor health. However, physical activity is reduced with increased age and only a fraction of older adults engages in resistance training (RT). Thus, strategies that facilitate RT among older adults are needed. The aim of the present study was to evaluate the effectiveness and user experience, and explore barriers and motivators toward an online delivered, home-based RT program in older adults with low muscle mass. Methods: Thirty men and women, 70-71 years of age with low muscle mass were assigned home-based RT with online exercise videos (3 times/week, 45 min/session for 10 weeks) accompanied with an initial supervised try-out session. Quantitative outcome measures included changes in lean body mass and physical function. Semi structured one-to-one interviews with a subset of the participants (n = 8) were also conducted to generate a greater understanding of the participants experience of the digitally supported RT. The material was transcribed and analyzed with qualitative content analysis. Results: Twenty-seven participants (90%) completed the trial. Lean body mass increased by 0.39 kg (95% CI: 0.06-0.72, p < 0.05) and chair stand time improved by 1.6 s (95% CI: 0.8-2.3, p < 0.001). No significant improvements were seen for balance or gait speed. The theme "Engaging in Digital Resistance Training with Personal Adaptation Leads to a Sense of Strength and Vitality" captured the participants experience of the intervention, where a sense of how the body was changing toward a more active lifestyle was described. Instructions, feedback, and intrinsic motivation were identified as key elements for compliance. Conclusion: The online delivered RT program for older adults with low muscle mass was feasible based on high compliance, user satisfaction, increased lean mass and improved chair-stand time. The participant experiences may explain the high compliance to the intervention and effects on outcomes. Based on these results, online delivered RT could be an accessible exercise routine for older adults with low muscle mass. More research is needed to verify the present findings and assess changes in a long-term perspective.

Short-term balance training and acute effects on postural sway in balance-deficient older adults: a randomized controlled trial.

BACKGROUND: We aimed to determine the effectiveness of 4 weeks of balance exercise compared with no intervention on objectively measured postural sway. METHODS: This was a single-center parallel randomized controlled, open label, trial. A six-sided dice was used for allocation at a 1:1-ratio between exercise and control. The trial was performed at a university hospital clinic in Sweden and recruited community-dwelling older adults with documented postural instability. The intervention consisted of progressively challenging balance exercise three times per week, during 4 weeks, with follow-up at week five. Main outcome measures were objective postural sway length during eyes open and eyes closed conditions. RESULTS: Sixty-five participants aged 70 years (balance exercise n = 32; no intervention n = 33) were randomized. 14 participants were excluded from analysis because of early dropout before follow-up at week five, leaving 51 (n = 22; n = 29) participants for analysis. No significant differences were detected between the groups in any of the postural sway outcomes. Within-group analyses showed significant improvements in hand grip strength for the intervention group, while Timed Up & Go improvements were comparable between groups but only statistically significant in the control group. CONCLUSIONS: Performing balance exercise over a four-week intervention period did not acutely improve postural sway in balance-deficient older adults. The lower limit in duration and frequency to achieve positive effects remains unclear. TRIAL REGISTRATION: Clinical trials NCT03227666 , July 24, 2017, retrospectively registered.

A multiple risk factor program is associated with decreased risk of cardiovascular disease in 70-year-olds: A cohort study from Sweden.

BACKGROUND: In individuals below 65 years of age, primary prevention programs have not been successful in reducing the risk of cardiovascular disease (CVD) and death. However, no large study to our knowledge has previously evaluated the effects of prevention programs in individuals aged 65 years or older. The present cohort study evaluated the risk of CVD in a primary prevention program for community-dwelling 70-year-olds. METHOD AND FINDINGS: In 2012-2017, we included 3,613 community-dwelling 70-year-olds living in Umeå, in the north of Sweden, in a health survey and multidimensional prevention program (the Healthy Ageing Initiative [HAI]). Classic risk factors for CVD were evaluated, such as blood pressure, lipid levels, obesity, and physical inactivity. In the current analysis, each HAI participant was propensity-score-matched to 4 controls (n = 14,452) from the general Swedish population using national databases. The matching variables included age, sex, diagnoses, medication use, and socioeconomic factors. The primary outcome was the composite of myocardial infarction, angina pectoris, and stroke. The 18,065 participants and controls were followed for a mean of 2.5 (range 0-6) years. The primary outcome occurred in 128 (3.5%) HAI participants and 636 (4.4%) controls (hazard ratio [HR] 0.80, 95% CI 0.66-0.97, p = 0.026). In HAI participants, high baseline levels of blood pressure and lipids were associated with subsequent initiation of antihypertensive and lipid-lowering therapy, respectively, as well as with decreases in blood pressure and lipids during follow-up. In an intention-to-treat approach, the risk of the primary outcome was lower when comparing all 70-year-olds in Umeå, regardless of participation in HAI, to 70-year-olds in the rest of Sweden for the first 6 years of the HAI project (HR 0.87, 95% CI 0.77-0.97, p = 0.014). In contrast, the risk was similar in the 6-year period before the project started (HR 1.04, 95% CI 0.93-1.17, p = 0.03 for interaction). Limitations of the study include the observational design and that changes in blood pressure and lipid levels likely were influenced by regression towards the mean. CONCLUSIONS: In this study, a primary prevention program was associated with a lower risk of CVD in community-dwelling 70-year-olds. With the limitation of this being an observational study, the associations may partly be explained by improved control of classic risk factors for CVD with the program.

Web-based exercise versus supervised exercise for decreasing visceral adipose tissue in older adults with central obesity: a randomized controlled trial.

BACKGROUND: Visceral adipose tissue (VAT) is a strong risk factor for cardiovascular disease and increases with age. While supervised exercise (SE) may be an effective approach, web-based exercise (WE) have other advantages such as being more readily accessible. Therefore, we evaluated the effects of WE on VAT, body composition and cardiometabolic risk markers in centrally obese older adults and compared the effects of WE to SE. We also explored the feasibility of WE. METHODS: In a randomized controlled trial conducted in Umeå, Sweden during January 2018 - November 2018, N = 77, 70-year-old men and women with central obesity (> 1 kg VAT for women, > 2 kg for men) were randomized to an intervention group (n = 38) and a wait-list control group (n = 39). The intervention group received 10 weeks of SE while the wait-list control group lived as usual. Following a 10-week wash-out-period, the wait-list control group received 10 weeks of WE. The primary outcome was changes in VAT. Secondary outcomes included changes in fat mass (FM), lean body mass (LBM), blood lipids, fasting blood glucose. Additionally, we explored the feasibility of WE defined as adherence and participant experiences. RESULTS: WE had no significant effect on VAT (P = 0.5), although it decreased FM by 450 g (95% confidence interval [CI], 37 to 836, P < 0.05). The adherence to WE was 85% and 87-97% of the participants rated aspects of the WE intervention > 4 on a scale of 1-5. Comparing SE to WE, there was no significant difference in decrease of VAT (Cohen's δ effect size [ES], 0.5, 95% CI, - 24 to 223, P = 0.11), although SE decreased FM by 619 g (ES, 0.5, 95% CI, 22 to 1215, P < 0.05) compared to WE. CONCLUSIONS: Ten weeks of vigorous WE is insufficient to decrease VAT in centrally obese older adults, but sufficient to decrease FM while preserving LBM. The high adherence and positive experiences of the WE intervention implies that it could serve as an alternative exercise strategy for older adults with central obesity, with increased availability for a larger population. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03450655), retrospectively registered February 28, 2018.

In vitro phagocytosis of liquid-stored red blood cells requires serum and can be inhibited with fucoidan and dextran sulphate.

BACKGROUND AND OBJECTIVES: Red-blood-cells (RBCs) undergo structural and metabolic changes with prolonged storage, which ultimately may decrease their survival after transfusion. Although the storage-induced damage to RBCs has been rather well described biochemically, little is known about the mechanisms underlying the recognition and rapid clearance of the damaged cells by macrophages. MATERIALS AND METHODS: We, here, used a murine model for cold (+4°C) RBC storage and transfusion. Phagocytosis of human or murine RBCs, liquid stored for 6-8 weeks or 10-14 days, respectively, was investigated in murine peritoneal macrophages. RESULTS: The effects of storage on murine RBCs resembled that described for stored human RBCs with regard to decreased adenosine triphosphate (ATP) levels, accumulation of microparticles (MPs) during storage, and RBC recovery kinetics after transfusion. Under serum-free conditions, phagocytosis of stored human or murine RBCs in vitro was reduced by 70-75%, as compared with that in the presence of heat-inactivated fetal calf serum (FCS). Human serum promoted phagocytosis of stored human RBCs similar to that seen with FCS. By adding fucoidan or dextran sulphate (blockers of scavenger receptors class A (SR-A)), phagocytosis of human or murine RBCs was reduced by more than 90%. Phagocytosis of stored human RBCs was also sensitive to inhibition by the phosphatidylinositol 3 kinase-inhibitor LY294002, the ERK1/2-inhibitor PD98059, or the p38 MAPK-inhibitor SB203580. CONCLUSION: RBCs damaged during liquid storage may be recognized by macrophage SR-A and serum-dependent mechanisms. This species-independent recognition mechanism may help to further understand the rapid clearance of stored RBCs shortly after transfusion.

Digital exercise interventions for improving measures of central obesity: a systematic review.

OBJECTIVES: We aimed to systematically review the potential benefits of digital exercise interventions for improving measures of central obesity including visceral adipose tissue (VAT) and anthropometric surrogates for VAT in overweight or centrally obese adults aged 18 or over. METHODS: A systematic literature search was conducted in three databases up until March 2020 (PROSPERO registration nr CRD42019126764). RESULTS: N = 5 studies including 438 participants (age 48-80) with body mass index ≥ 25 kg/m2 met the eligibility criteria and were included. The duration of the interventions ranged from 8 to 24 weeks. No study measured the primary outcome VAT, although in N = 4 studies, waist circumference (WC) decreased by between 1.3 and 5.6 cm in the intervention groups. CONCLUSIONS: This systematic review shows that there is no evidence for the effects of digital exercise on VAT, although digital exercise may decrease WC. These findings highlight the need for additional randomized controlled trials to confirm the findings with respect to WC, and to further investigate the effects of digital exercise on VAT. Together, this may have important implications for reducing the burden of physical inactivity and obesity.

Effects of interval training on quality of life and cardiometabolic risk markers in older adults: a randomized controlled trial.

PURPOSE: To explore the effects of 10 weeks of progressive vigorous interval training as a single intervention on health-related quality of life (HRQoL) and cardiometabolic risk markers in centrally obese 70-year-old individuals. PARTICIPANTS AND METHODS: A randomized controlled trial (ClinicalTrials.gov registration no. NCT03450655) including seventy-seven community-dwelling 70-year-old men and women with central obesity defined as > 1 kg visceral adipose tissue for women and > 2 kg for men. Participants randomized to the intervention group were offered a 10-week progressive vigorous interval training program performed three times per week. Control subjects were asked to maintain their daily living and routines throughout the trial. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation. Prespecified outcome measures included: changes in HRQoL using the Short Form Health Survey Questionnaire (SF-36), blood pressure; resting heart rate (HR) and blood lipids. All analyses were conducted on an intention-to-treat basis. RESULTS: The intervention resulted in significant effects on the SF-36 mental component summary (MCS) score and the mental health (MH) subscale (P< 0.05 for both), when compared to the control group. Specifically, the intervention group increased their MCS score by 6.3 points (95% confidence interval [CI] = 0.3-12.3) and their MH score by 6.0 points (95% CI = 1.7-10.4) compared to the control group. Moreover, significant effects were seen on resting HR, total cholesterol and LDL-cholesterol (P<0.05 for all). CONCLUSION: It was shown that 10 weeks of vigorous interval training as a single intervention was sufficient to improve mental aspects of HRQoL in older individuals with central obesity, which is a critical aspect of healthy ageing. Positive effects were seen also on cardiometabolic risk markers.

Objectively Measured Physical Activity in Older Adults With and Without Diabetes.

In Brief People with known diabetes were found to be 20% less active than people without diabetes as measured by objective accelerometers. A threshold of 6,000 steps per day was associated with the lowest risk of prevalent diabetes. The study also emphasizes the use of objective techniques to measure physical activity in subjects with diabetes.

Effects of Interval Training on Visceral Adipose Tissue in Centrally Obese 70-Year-Old Individuals: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of 10 weeks of progressive vigorous-intensity interval training as a single intervention on body composition among 70-year-old individuals with central obesity. DESIGN: Randomized controlled trial (ClinicalTrials.gov registration No. NCT03450655). SETTING: Community-dwelling 70-year-old men and women living in the Umeå municipality in Sweden. PARTICIPANTS: Seventy-seven 70-year-old men and women with central obesity (greater than 1 kg visceral adipose tissue [VAT] for women and greater than 2 kg VAT for men). INTERVENTION: Participants allocated to the intervention group were offered a 10-week progressive concurrent exercise program performed three times per week. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation. MEASUREMENTS: The primary outcome was changes in VAT, and secondary outcomes included changes in total fat mass (FM), total lean body mass (LBM), and body mass index. RESULTS: Comparing the groups, there were no significant differences in decrease of VAT mass (P = .10), although the intervention group significantly decreased FM by 716 g (P = .01) and gained LBM by 508 g (P = .03), compared to the control group. Furthermore, the effects of the training were significantly greater in the male subcohort (P < .05 for interaction), with positive effects also on VAT and FM, where men in the intervention group decreased VAT by 175 g (P < .05) and FM by 1364 g (P = .004), compared to the male controls. CONCLUSIONS: The present trial demonstrates that 10 weeks of progressive vigorous interval training is sufficient to significantly decrease FM in older adults with central obesity, with positive effects also on LBM. J Am Geriatr Soc 67:1625-1631, 2019.

Effects of Resistance Training on Functional Strength and Muscle Mass in 70-Year-Old Individuals With Pre-sarcopenia: A Randomized Controlled Trial.

OBJECTIVE: Sarcopenia has been defined as age-related loss of muscle mass and function. The aim of this randomized controlled trial was to examine the effects of a 10-week instructor-led resistance training program on functional strength and body composition in men and women aged 70 years with pre-sarcopenia. DESIGN, SETTING, AND PARTICIPANTS: Participants were randomized to either 10 weeks of a physical training regimen including optional nutritional supplementation (n = 36) or to a control group (n = 34) (ClinicalTrials.gov, no. NCT03297632). The main outcome was changes in the Short Physical Performance Battery (SPPB) score. Secondary outcomes included the Timed Up and Go test, chair sit-stand time, lean body mass, and fat mass. RESULTS: The intervention had no significant effect on SPPB in the total cohort (P = .18), when comparing changes in the intervention group with the control group. However, those given the intervention in the male subcohort increased 0.5 ± 0.4 (mean ± standard error for the difference) points in SPPB during follow-up (P = .02) compared to male controls. With respect to secondary outcomes, the intervention group decreased 0.9 ± 0.6 seconds in chair sit-stand time compared to controls (P = .01). Furthermore, the intervention resulted in significantly greater improvements for the training group than control group in all measures of body composition (P ≤ .01 for all). For example, lean body mass increased by a mean of 1147 ± 282 g (P < .001), and total fat mass decreased by a mean of 553 ± 225 g (P = .003), favoring the intervention group. CONCLUSION/IMPLICATIONS: The main finding of this intervention study is that an easy-to-use, functional resistance training program was effective in maintaining functional strength and increasing muscle mass in older adults with pre-sarcopenia.

Self-reported protein intake and properties of bone in community-dwelling older individuals.

This study revealed that a quick and simple estimation of protein intake was related to measures of bone density and area in 70-year-old individuals. Furthermore, these associations were mediated by muscle mass when investigating peripheral measurement sites such as arms and legs. PURPOSE: Recent evidence suggests that dietary protein is beneficial for bone health in older individuals, but less is known about the influence of muscle mass on this relationship. This cross-sectional study aimed to investigate associations among protein intake, bone health, and muscle mass in 2332 men and women aged 70 years. METHODS: Volumetric bone mineral density of the radius and tibia was measured using peripheral quantitative computed tomography. Using dual-energy X-ray absorptiometry, we measured areal bone mineral density (aBMD) at the L1-L4 vertebrae, radius, and femoral neck, together with appendicular lean mass. Participants reported their average meal size and proportion of meat/fish intake. Associations were investigated using multiple linear regression models, adjusted for multiple covariates. RESULTS: Self-reported protein intake was associated with aBMD of the femoral neck (ß = 0.082) and L1-L4 vertebrae (ß = 0.063) in men (both p < 0.05) after adjusting for multiple covariates, including appendicular muscle mass. No significant association was detected among women. In addition, protein intake was associated with tibial cortical area (ß = 0.08), periosteal circumference (ß = 0.072), radial aBMD (ß = 0.064), and trabecular area (ß = 0.078) in men (all p < 0.05), although these associations were attenuated after adjustment for appendicular muscle mass (all p > 0.05). CONCLUSION: Self-reported protein intake was associated with bone properties in 70-year-old men. The strength of these associations in peripheral bone sites may be partially mediated by muscle mass from protein intake.

Dairy product intake and bone properties in 70-year-old men and women.

In the present population-based study including 70-year-old men and women, total dairy product intake was associated with a weak positive association with tibia trabecular and cortical cross-sectional areas. PURPOSE: Milk consumption has recently been suggested to increase fracture risk. Therefore, we aimed to investigate associations between dairy product consumption and peripheral bone properties. Furthermore, we explored whether consumption of milk and fermented dairy products affected bone properties differently. METHODS: The Healthy Aging Initiative is a population-based, cross-sectional study investigating the health of 70-year-old men and women. Out of the 2904 individuals who met the inclusion criteria, data on self-reported daily dairy product consumption (dl/day), peripheral quantitative computed tomography (pQCT) examinations at the 4 and 66% scan sites of the tibia and radius, and dual-energy X-ray absorptiometry (DXA) scans were collected from 2040 participants. Associations between dairy product consumption and bone properties were examined using multiple linear regression models adjusted for sex, muscle area, meal size, dietary protein proportion, current smoking status, and objectively measured physical activity. RESULTS: Total dairy product intake was associated with larger trabecular (2.296 (95% CI, 0.552-4.039) mm2, per dl/day increase, p = 0.01) and cortical cross-sectional areas (CSAs) in the tibia (1.757 (95% CI, 0.683-2.830 mm2, p = 0.001) as measured by pQCT and higher areal bone mineral density (aBMD) of the radius (3.231 (95% CI, 0.764-5.698) mg/cm2, p = 0.01) as measured by DXA. No other measurement in the tibia, radius, femoral neck, or lower spine was associated significantly with dairy product intake. Bone properties did not differ according to the type of dairy product consumed. CONCLUSION: No evidence of a negative association between dairy product consumption and bone health was found. Furthermore, total dairy product consumption was associated with increased CSAs in the tibia, regardless of dairy product type. Collectively, our findings indicate the existence of a weak but significant positive association between dairy product consumption bone properties in older adults.

Autologous Doping with Cryopreserved Red Blood Cells - Effects on Physical Performance and Detection by Multivariate Statistics.

The discovery of erythropoietin (EPO) simplified blood doping in sports, but improved detection methods, for EPO has forced cheating athletes to return to blood transfusion. Autologous blood transfusion with cryopreserved red blood cells (RBCs) is the method of choice, because no valid method exists to accurately detect such event. In endurance sports, it can be estimated that elite athletes improve performance by up to 3% with blood doping, regardless of method. Valid detection methods for autologous blood doping is important to maintain credibility of athletic performances. Recreational male (N = 27) and female (N = 11) athletes served as Transfusion (N = 28) and Control (N = 10) subjects in two different transfusion settings. Hematological variables and physical performance were measured before donation of 450 or 900 mL whole blood, and until four weeks after re-infusion of the cryopreserved RBC fraction. Blood was analyzed for transferrin, iron, Hb, EVF, MCV, MCHC, reticulocytes, leucocytes and EPO. Repeated measures multivariate analysis of variance (MANOVA) and pattern recognition using Principal Component Analysis (PCA) and Orthogonal Projections of Latent Structures (OPLS) discriminant analysis (DA) investigated differences between Control and Transfusion groups over time. Significant increase in performance (15 ± 8%) and VO2max (17 ± 10%) (mean ± SD) could be measured 48 h after RBC re-infusion, and remained increased for up to four weeks in some subjects. In total, 533 blood samples were included in the study (Clean = 220, Transfused = 313). In response to blood transfusion, the largest change in hematological variables occurred 48 h after blood donation, when Control and Transfused groups could be separated with OPLS-DA (R2 = 0.76/Q2 = 0.59). RBC re-infusion resulted in the best model (R2 = 0.40/Q2 = 0.10) at the first sampling point (48 h), predicting one false positive and one false negative. Over all, a 25% and 86% false positives ratio was achieved in two separate trials. In conclusions, autologous re-infusion of RBCs increased VO2max and performance as hypothesized, but hematological profiling by multivariate statistics could not reach the WADA stipulated false positive ratio of <0.001% at any time point investigated. A majority of samples remained within limits of normal individual variation at all times.

Red blood cells with elevated cytoplasmic Ca(2+) are primarily taken up by splenic marginal zone macrophages and CD207+ dendritic cells.

BACKGROUND: The normal red blood cell (RBC) life span may be significantly reduced when RBCs are stored under blood bank conditions, resulting in a reduced 24-hour survival after transfusion. The damage of stored RBCs is probably multifactorial as stored RBCs share features of both senescence and suicidal RBC death (eryptosis). Since an increased intracellular Ca(2+) concentration ([Ca(2+) ]i ) is one key feature of eryptosis, we here investigated if stored human RBCs had increased [Ca(2+) ]i and the mechanisms behind uptake of such RBCs in a murine model. STUDY DESIGN AND METHODS: The intracellular Ca(2+) content of RBCs was determined using the Ca(2+) probe Fluo-3 and flow cytometry. In vivo uptake of Ca(2+) ionophore-treated murine RBCs (Ca(2+) -RBCs) was investigated in recipient mice, using flow cytometry and immunohistochemical analysis. RESULTS: A small fraction of human RBCs accumulated [Ca(2+) ]i during storage for up to 42 days under blood bank conditions. In a murine model, where fresh or Ca(2+) -RBCs were transfused, Ca(2+) -RBCs were mainly trapped by MARCO+ splenic marginal zone macrophages and CD11c+ CD207+ dendritic cells (DCs) within 1 hour after transfusion. In marked contrast, freshly transfused RBCs aging normally in circulation were cleared much slower and preferentially by F4/80+ red pulp macrophages. CD47 on the Ca(2+) -RBCs did not affect their clearance by splenic phagocytic cells. CONCLUSIONS: A small fraction of RBCs accumulate [Ca(2+) ]i during storage, and in a murine model such RBCs are recognized by splenic macrophages and DCs in ways similar to what has been reported for nucleated apoptotic cells.

Transfusion of cryopreserved human red blood cells into healthy humans is associated with rapid extravascular hemolysis without a proinflammatory cytokine response.

BACKGROUND: Transfusion of stored red blood cells (RBCs) can be associated with adverse side effects. Recent studies in mice transfused with stored RBCs showed that a strong proinflammatory cytokine storm was induced due to extravascular hemolysis already at 2 hours after transfusion. Therefore, we here investigated if transfusion of 2 units of cryopreserved autologous RBCs induced a proinflammatory response in healthy human volunteers. STUDY DESIGN AND METHODS: Two units of autologous RBCs, cryopreserved for 16 weeks, were transfused into 10 healthy human volunteers. Serum and blood samples taken at 2 hours before and at 2 and 48 hours after transfusion were analyzed for signs of extravascular hemolysis and the presence of proinflammatory cytokines. RESULTS: At 2 hours after transfusion, transferin-bound serum iron, as well as transferin saturation and total bilirubin, were already significantly increased. These measures all returned back toward that in pretransfusion samples at 48 hours after transfusion. No increases in the production of the proinflammatory cytokines interleukin (IL)-1ß, IL-6, IL-8, monocyte chemotactic protein-1, macrophage inflammatory protein-1ß, or tumor necrosis factor-α were detected at any time point after transfusion. CONCLUSION: Although a significant level of extravascular hemolysis already occurred at 2 hours after transfusion of cryopreserved RBCs, there were no signs of proinflammatory cytokine production up to 48 hours after transfusion.