• all-cause mortality
• arterial oxygen partial pressure
• cardiac surgery

• Humans
• Retrospective Studies
• Cardiac Surgical Procedures/mortality
• Cardiac Surgical Procedures/trends
• Cardiac Surgical Procedures/adverse effects
• Male
• Female
• Aged
• Middle Aged
• Hospital Mortality/trends
• Critical Care/methods
• Critical Care/trends
• Cohort Studies
• Oxygen/blood
• Follow-Up Studies
• Postoperative Complications/mortality
• Postoperative Complications/blood

• Cryopreservation
• Nanoprotectant
• Red blood cell biopreservation
• Refrigeration storage
• Storage lesion

• Erythrocytes/cytology
• Humans
• Cryopreservation/methods
• Nanostructures/chemistry
• Blood Preservation/methods
• Refrigeration

• 22372061 National Natural Science Foundation of China
• 2019QN01Y314 Guangdong Provincial Pearl River Talents Program
• 2019ZT08Y318 Program for Guangdong Introducing Innovative and Entrepreneurial Teams
• 2021 A1515220051 Natural Science Foundation of Guangdong Province, China
• 2024KQNCX005 Program for Young Innovation Talents in Higher Education of Guangdong Province, China
• Fundamental Research Funds for the Central Universities of China

• Krogh cylinder
• Microcirculation
• Phosphorescence quenching microscopy
• Storage lesion
• Transfusion

• Animals
• Mesocricetus
• Oxygen/metabolism
• Cricetinae
• Microvessels/diagnostic imaging
• Erythrocytes/metabolism
• Models, Cardiovascular
• Male
• Luminescent Measurements/methods
• Diffusion
• Intravital Microscopy

• R01 HL126945 NHLBI NIH HHS
• R01 HL138116 NHLBI NIH HHS

• blood cell
• computational fluid dynamics
• haemodynamics
• machine learning
• microcirculation

• Blood Flow Velocity/physiology
• Capillaries/physiology
• Erythrocytes
• Hematocrit
• Hemodynamics
• Machine Learning

• R01 EY033003 NEI NIH HHS
• National Institute of Health

Capillary blood vessels, the smallest vessels in the body, form an intricate network with constantly bifurcating, merging and winding vessels. Red blood cells (RBCs) must navigate through such complex microvascular networks in order to maintain tissue perfusion and oxygenation. Normal, healthy RBCs are extremely deformable and able to easily flow through narrow vessels. However, RBC deformability is reduced in many pathological conditions and during blood storage. The influence of reduced cell deformability on microvascular hemodynamics is not well established. Here we use a high-fidelity, 3D computational model of blood flow that retains exact geometric details of physiologically realistic microvascular networks, and deformation of every one of nearly a thousand RBCs flowing through the networks. We predict that reduced RBC deformability alters RBC trafficking with significant and heterogeneous changes in hematocrit. We quantify such changes along with RBC partitioning and lingering at vascular bifurcations, perfusion and vascular resistance, and wall shear stress. We elucidate the cellular-scale mechanisms that cause such changes. We show that such changes arise primarily due to the altered RBC dynamics at vascular bifurcations, as well as cross-stream migration. Less deformable cells tend to linger less at majority of bifurcations increasing the fraction of RBCs entering the higher flow branches. Changes in vascular resistance also seen to be heterogeneous and correlate with hematocrit changes. Furthermore, alteration in RBC dynamics is shown to cause localized changes in wall shear stress within vessels and near vascular bifurcations. Such heterogeneous and focal changes in hemodynamics may be the cause of morphological abnormalities in capillary vessel networks as observed in several diseases.

• biophysical phenotyping
• microcirculation
• microfluidics
• oxidative stress
• red blood cells

• Anemia/blood
• Anemia/chemically induced
• Anemia/etiology
• Anemia/pathology
• Erythrocyte Count
• Erythrocytes/drug effects
• Erythrocytes/pathology
• Humans
• Hydrogen Peroxide/metabolism
• Microcirculation/drug effects
• Microfluidic Analytical Techniques
• Neoplasms/blood
• Neoplasms/complications
• Neoplasms/drug therapy
• Oxidative Stress/drug effects
• Oxidative Stress/genetics
• tert-Butylhydroperoxide/pharmacology

• Raman spectroscopy
• erythrocytes
• hemoglobin
• living cells
• membrane proteins
• metal nanoparticles

• Cell Membrane/metabolism
• Erythrocytes/metabolism
• Hemoglobins/analysis
• Humans
• Metal Nanoparticles/chemistry
• Particle Size
• Silver/chemistry
• Spectrum Analysis, Raman

during the storage of transfusion blood, it may undergo a series of cellular changes that in speculation could be the reason behind the risk of using prolonged stored blood. It's important therefore to monitor the cellular changes that may reduce its survival and function. The objective was to assess the cellular changes in whole blood stored for transfusion at Bungoma county referral hospital.

a single center, prospective and observational study design involving 20 randomly selected donor blood units in citrate phosphate dextrose adenine (CPDA-1) anticoagulant was employed, cellular changes were evaluated for 35 days. The changes were tested using the Celtac F Haematology analyzer. Statistical Analysis of variance was employed in the descriptive statistics. All the investigation was executed using statistical package for social sciences (SPSS V.23). Results were regarded as significant at P<0.05. Results were presented in tables and charts.

at the end of the 35 days blood storage at blood bank conditions, WBC, RBC, platelets counts and MCHC decreased significantly (P<0.0001, =0.0182, <0.0001, =0.0035). The MCV, HCT and MCH increased significantly (P <0.0001, =0.0003, =0.0115) while HGB had insignificant variance (P =0.4185).

platelets, WBC, RBC counts, and indices are significantly altered in stored blood especially when stored over two weeks based on most of the cellular components analyzed in this study. The study, therefore, recommends the utilization of fresh blood to avoid the adverse outcome of cellular changes of reserved blood.

• Blood transfusion
• Kenya
• cellular changes
• storage

During storage, transfusion blood may undergo a series of biochemical changes that could pose risks to patients when used. It is important therefore to monitor biochemical changes that may reduce survival or function of stored blood cells.

This study assessed biochemical changes in whole blood stored for transfusion at Bungoma County Referral Hospital in the western region of Kenya between February 2019 and August 2019.

A prospective study design involving 20 randomly selected donor blood units in citrate phosphate dextrose adenine anticoagulant was employed. Biochemical changes were evaluated for 35 days. Potassium and sodium levels were tested using the HumaLyte Plus5 analyser. Blood pH level was estimated using the Hanna pH meter.

At the end of the 35 days of storage under blood bank conditions, the mean potassium level significantly increased from 7.31 mmol/L at baseline to 20.14 mmol/L at week 5 (p < 0.0001), and the mean sodium level significantly decreased from 150.72 mmol/L at baseline to 121.56 mmol/L at week 5 (p < 0.0001). The pH level decreased insignificantly from 7.48 at baseline to 7.38 at the end of week 1 (p = 0.0757) but decreased significantly to 6.15 at the end of week 5 (p < 0.0001).

Potassium increased and sodium concentrations decreased significantly from the first week of blood storage. The pH decreased significantly from the second week of storage. Therefore, aged blood should be avoided to circumvent potential adverse outcomes from biochemical changes and stored blood should be tested before use.

• Kenya
• biochemical changes
• blood
• storage
• transfusion

• cytoskeleton nanostructure
• long-term storage
• membrane stiffness
• pRBCs
• storage lesion

• Blood Preservation/methods
• Cell Adhesion/physiology
• Endothelium, Vascular/physiology
• Erythrocytes/physiology
• Glycocalyx/metabolism
• Humans
• Microcirculation/physiology
• Microfluidics/methods
• Shock, Hemorrhagic/physiopathology
• Stress, Physiological/physiology

• Engineering
• Other photonics

• P01 HL086773 NHLBI NIH HHS
• R01 HL095479 NHLBI NIH HHS
• R21 ES029791 NIEHS NIH HHS
• U.S. Department of Health & Human Services | National Institutes of Health (NIH)
• National Science Foundation (NSF)

• blood transfusion
• blood banking
• storage lesion
• clinical sequelae

• Blood Preservation
• Erythrocyte Transfusion/adverse effects
• Erythrocyte Transfusion/methods
• Erythrocytes/cytology
• Erythrocytes/metabolism
• Humans
• Oxygen/metabolism
• Pharmaceutical Solutions/pharmacology
• Time Factors

• R44 HL132172 NHLBI NIH HHS

• Blood
• Cardiac surgery
• Complications
• Oxidation reduction potential
• Pediatrics
• Red blood cells

• Banked blood
• blood storage
• blood transfusion
• deformability
• storage lesions

BACKGROUND: Erythrocytes undergo irreversible morphological and biochemical changes during storage. Reduced levels of deformability have been reported for stored erythrocytes. Erythrocyte deformability is essential for healthy microcirculation.

OBJECTIVE: The aim of this study is to evaluate shear stress (SS) induced improvements of erythrocyte deformability in stored blood.

METHODS: Deformability changes were evaluated by applying physiological levels of SS (5 and 10 Pa) in metabolically depleted blood for 48 hours and stored blood for 35 days with citrate phosphate dextrose adenine-1 (CPDA-1). Laser diffractometry was used to measure erythrocyte deformability before and after application of SS.

RESULTS: Erythrocyte deformability, as a response to continuous SS, was significantly improved in metabolically depleted blood, whereas it was significantly impaired in the blood stored for 35 days with CPDA-1 (p≤0.05). The SS-induced improvements of deformability were deteriorated due to storage and relatively impaired according to the storage time. However, deformability of stored blood after exposure to mechanical stress tends to increase at low levels of shear while decreasing at high SS levels.

CONCLUSION: Impairment of erythrocyte deformability after storage may contribute to impairments in the recipient’s microcirculation after blood transfusion. The period of the storage should be considered to prevent microcirculatory problems and insufficient oxygen delivery to the tissues.

• CPDA-1
• Erythrocyte deformability
• blood storage
• metabolic depletion
• shear stress

• Blood Preservation/methods
• Erythrocyte Deformability/physiology
• Erythrocytes/physiology
• Humans
• Stress, Mechanical

Hyperoxia has long been perceived as a desirable or at least an inevitable part of cardiopulmonary bypass. Recent evidence suggest that it might have multiple detrimental effects on patient homeostasis. The aim of the study was to identify the determinants of supra-physiological values of partial oxygen pressure during on-pump cardiac surgery and to assess the impact of hyperoxia on clinical outcomes.

Retrospective data analysis of the institutional research database was performed to evaluate the effects of hyperoxia in patients undergoing elective cardiac surgery with cardiopulmonary bypass, 246 patients were included in the final analysis. Patients were divided in three groups: mild hyperoxia (MHO, PaO₂ 100–199 mmHg), moderate hyperoxia (MdHO, PaO₂ 200–299 mmHg), and severe hyperoxia (SHO, PaO₂ >300 mmHg). Postoperative complications and outcomes were defined according to standardised criteria of the Society of Thoracic Surgeons.

The extent of hyperoxia was more immense in patients with a lower body mass index (p = 0.001) and of female sex (p = 0.005). A significant link between severe hyperoxia and a higher incidence of infectious complications (p – 0.044), an increased length of hospital stay (p – 0.044) and extended duration of mechanical ventilation (p < 0.001) was confirmed.

Severe hyperoxia is associated with an increased incidence of postoperative infectious complications, prolonged mechanical ventilation, and increased hospital stay.

• Hyperoxia
• cardiac surgery
• cardiopulmonary bypass
• infectious complications
• reactive oxygen species

To investigate the microvascular (skeletal muscle tissue oxygenation; SmO₂) response to transfusion in patients undergoing elective complex spine surgery.

After IRB approval and written informed consent, 20 patients aged 18 to 85 years of age undergoing > 3 level anterior and posterior spine fusion surgery were enrolled in the study. Patients were followed throughout the operative procedure, and for 12 h postoperatively. In addition to standard American Society of Anesthesiologists monitors, invasive measurements including central venous pressure, continual analysis of stroke volume (SV), cardiac output (CO), cardiac index (CI), and stroke volume variability (SVV) was performed. To measure skeletal muscle oxygen saturation (SmO₂) during the study period, a non-invasive adhesive skin sensor based on Near Infrared Spectroscopy was placed over the deltoid muscle for continuous recording of optical spectra. All administration of fluids and blood products followed standard procedures at the Hospital for Special Surgery, without deviation from usual standards of care at the discretion of the Attending Anesthesiologist based on individual patient comorbidities, hemodynamic status, and laboratory data. Time stamps were collected for administration of colloids and blood products, to allow for analysis of SmO₂ immediately before, during, and after administration of these fluids, and to allow for analysis of hemodynamic data around the same time points. Hemodynamic and oxygenation variables were collected continuously throughout the surgery, including heart rate, blood pressure, mean arterial pressure, SV, CO, CI, SVV, and SmO₂. Bivariate analyses were conducted to examine the potential associations between the outcome of interest, SmO₂, and each hemodynamic parameter measured using Pearson’s correlation coefficient, both for the overall cohort and within-patients individually. The association between receipt of packed red blood cells and SmO₂ was performed by running an interrupted time series model, with SmO₂ as our outcome, controlling for the amount of time spent in surgery before and after receipt of PRBC and for the inherent correlation between observations. Our model was fit using PROC AUTOREG in SAS version 9.2. All other analyses were also conducted in SAS version 9.2 (SAS Institute Inc., Cary, NC, United States).

Pearson correlation coefficients varied widely between SmO₂ and each hemodynamic parameter examined. The strongest positive correlations existed between ScvO₂ (P = 0.41) and SV (P = 0.31) and SmO₂; the strongest negative correlations were seen between albumin (P = -0.43) and cell saver (P = -0.37) and SmO₂. Correlations for other laboratory parameters studied were weak and only based on a few observations. In the final model we found a small, but significant increase in SmO₂ at the time of PRBC administration by 1.29 units (P = 0.0002). SmO₂ values did not change over time prior to PRBC administration (P = 0.6658) but following PRBC administration, SmO₂ values declined significantly by 0.015 units (P < 0.0001).

Intra-operative measurement of SmO₂ during large volume, yet controlled hemorrhage, does not show a statistically significant correlation with either invasive hemodynamic, or laboratory parameters in patients undergoing elective complex spine surgery.

• Transfusion
• Complex spine surgery
• Near infrared spectroscopy
• Microvascular blood flow
• Hemodynamic monitoring

• Fluid–cell interaction
• Multiscale modeling
• RBC translocation
• Spleen

• Clinical relevance
• Donor variation
• Extracellular vesicles
• Omics
• Red blood cell storage lesion

• U01 AA021902 NIAAA NIH HHS

• red blood cell aggregation
• hyperthermia
• plasma viscosity
• red blood cell deformability

• Adult
• Blood Viscosity/physiology
• Body Temperature/physiology
• Cell Aggregation/physiology
• Dehydration/physiopathology
• Erythrocyte Membrane/physiology
• Erythrocytes/physiology
• Exercise/physiology
• Female
• Fever/physiopathology
• Hematocrit/methods
• Hot Temperature
• Humans
• Male

• R01 HL052684 NHLBI NIH HHS
• T32 HL105373 NHLBI NIH HHS
• P01 HL110900 NHLBI NIH HHS
• R56-HL123015 NHLBI NIH HHS
• R01-HL52684 NHLBI NIH HHS
• P01-HL110900 NHLBI NIH HHS
• R56 HL123015 NHLBI NIH HHS

Blood transfusions are used to treat reduced O₂-carrying capacity consequent to anemia. In many cases anemia is caused by a major blood loss, which also creates a state of hypovolemia. Whereas O₂ transport capacity is restored by increasing levels of circulating Hb, transfusion does not resolve the hypoperfusion, the hypoxia and the inflammatory cascades initiated during the anemia and hypovolemia. This explains why blood transfusion is not always an effective treatment and why transfusion of stored blood has been associated with increased morbidity and mortality, especially in patient populations receiving multiple transfusions. Epidemiologic data indicate that adverse events after transfusion are relatively common, having a great impact on the patients outcome and on the costs of public health. In this chapter, we explain why classical transfusion strategies target the reversal of hypoxia only, but do not address the inflammatory cascades initiated during anemic states and the importance of the flow and vascular endothelium interactions. We also establish the relation between red blood cells storage lesions, limited NO bioavailability and transfusion-associated adverse events. Lastly, we explain the potential use of long-lived sources of bioactive NO to reverse the hypoxic inflammatory cascades, promote a sustained increase in tissue perfusion and thereby allow transfusions to achieve their intended goal. The underlying premise is that adverse effects associated with transfusions are intimately linked to vascular dysfunction. Understanding of these mechanisms would lead to novel transfusion medicine strategies to preserve red cell function and to correct for functional changes induced by hemoglobinopathies that affect cell structure and function.

• blood transfusion
• hemorrhagic shock
• no releasing nanoparticles
• red blood cells

• Aged
• Blood Transfusion
• Female
• Hemodynamics
• Hemoglobins/metabolism
• Humans
• Male
• Microcirculation
• Microvessels/metabolism
• Middle Aged
• Pulmonary Gas Exchange
• Sepsis/blood
• Sepsis/physiopathology
• Sepsis/therapy

• Blood Preservation
• Blood Transfusion
• Erythrocytes/cytology
• Erythrocytes/physiology
• Humans

• Hemodynamics
• Hemorrhage
• Immunomodulation
• Microvascular
• Randomized controlled trial
• Red blood cell
• Storage lesion
• Transfusion
• Trauma

Many premature babies, especially those with a low birth weight are given multiple transfusions during their first few weeks of life. The major serious complications of prematurity include bronchopulmonary dysplasia, with lesser incidences of retinopathy of prematurity, intraventricular haemorrhage, and necrotising enterocolitis. Many studies have shown correlations between the receipt of blood transfusions and the development of these conditions, but little is known of the underlying pathophysiology of this relationship. Recent studies are beginning to provide some answers. This review examines recent findings with regard to the influence of preparation and storage of paediatric packed red blood cell units on heme, iron, and oxidative status of the units and relates these to the ability of the premature baby to deal with these changes following the receipt of blood transfusions. Paediatric packed red blood cell units are a potential source of heme, redox active iron and free radicals, and this increases with storage age. Haemolysis of transfused red blood cells may add further iron and cell free haemoglobin to the recipient baby. Premature babies, particularly those with low birth weight and gestational age appear to have little reserve to cope with any additional iron, heme and/or oxidative load. The consequences of these events are discussed with regard to their contribution to the major complications of prematurity and a novel hypothesis regarding transfusion-related morbidity in premature babies is presented. The review concludes with a discussion of potential means of limiting transfusion related iron/heme and oxidative load through the preparation and storage of packed red blood cell units and through modifications in clinical practice.

• Blood transfusions
• Premature babies
• Iron
• Heme
• Oxidative stress
• Storage lesion
• Complications of prematurity