Hematopoietic stem cells surrender organelles during differentiation, leaving mature red blood cells (RBC) devoid of transcriptional machinery and mitochondria. The resultant absence of cellular repair capacity limits RBC circulatory longevity, and old cells are removed from circulation. The specific age-dependent alterations required for this apparently targeted removal of RBC, however, remain elusive.
View Article and Find Full Text PDFJ Heart Lung Transplant
November 2024
Mechanical circulatory support devices have profoundly transformed the management of severe cardiothoracic disorders. While heart transplantation is the gold standard therapy for end-stage heart disease, long-term mechanical support devices are a viable alternative for those ineligible and/or those awaiting organ availability. Major technological advancements were made over first 5 decades of development, resulting in improved durability and survival with reduced adverse events.
View Article and Find Full Text PDFBackground: Von Willebrand factor (VWF) is a critical glycoprotein in hemostasis and is an important factor in diagnosing bleeding disorders. Albeit the analysis of VWF is often compromised by inconsistent methodologies and challenges quantifying multimeric size. Current VWF multimer analysis methods are costly, time-consuming, and often inconsistent; thus, demanding skilled professionals.
View Article and Find Full Text PDFEx vivo hemocompatibility testing is a vital element of preclinical assessment for blood-contacting medical devices. Current approaches are resource intensive; thus, we investigated the feasibility of accelerating hemocompatibility testing by standardizing the number of pump exposures in loops of various sizes. Three identical blood loops were constructed, each with a custom-molded reservoir able to facilitate large-volume expansion.
View Article and Find Full Text PDFObstructive sleep apnoea (OSA) is a prevalent disorder that causes repetitive, temporary collapses of the upper airways during sleep, resulting in intermittent hypoxaemia and sleep fragmentation. Given those with OSA also exhibit decreased blood fluidity, this clinical population is at heightened risk for cardiovascular disease (CVD) development. Continuous positive airway pressure (CPAP) remains a primary therapy in OSA, which improves sleep quality and limits sleep fragmentation.
View Article and Find Full Text PDFBlood is a complex fluid owing to its two-phase suspension of formed cellular elements within a protein-rich plasma. Vital to its role in distributing nutrients throughout the circulatory system, the mechanical properties of blood - and particularly red blood cells (RBC)-primarily determine bulk flow characteristics and microcirculatory flux. Various factors impair the physical properties of RBC, including cellular senescence, many diseases, and exposure to mechanical forces.
View Article and Find Full Text PDFInertial microfluidics functions solely based on the fluid dynamics at relatively high flow speed. Thus, channel geometry is the critical design parameter that contributes to the performance of the device. Four basic channel geometries (, straight, expansion-contraction, spiral and serpentine) have been proposed and extensively studied.
View Article and Find Full Text PDFAnimal blood products are routinely used as surrogates for human tissue in haemocompatibility testing of rotary blood pumps. Bovine blood is particularly attractive due to the animal's large blood volume; however, bovine red blood cells (RBC) differ substantially from those of human, both in biophysical properties and molecular composition. We aimed to determine whether differences also exist in the sensitivity of bovine RBC to a standardised shear stress protocol.
View Article and Find Full Text PDFInvestigating flowing red blood cell (RBC) morphology and orientation is important for elucidating physiology and disease; existing commercially available products are limited to observing cell populations or single cells. In this protocol, we create a custom apparatus that combines coaxial brightfield microscopy with laser diffractometry to inspect near-real-time deformability, morphology, and orientation of flowing RBCs. There are difficulties associated with building optical systems for biological inspection; however, this protocol provides a suitable framework for developing an "ektacytoscope" for studying blood cells.
View Article and Find Full Text PDFPlasma extraction from blood is essential for diagnosis of many diseases. The critical process of plasma extraction requires removal of blood cells from whole blood. Fluid viscoelasticity promotes cell migration towards the central axis of flow due to differences in normal stress and physical properties of cells.
View Article and Find Full Text PDFThe viscoelastic properties of red blood cells (RBC) facilitate flexible shape change in response to extrinsic forces. Their viscoelasticity is intrinsically linked to physical properties of the cytosol, cytoskeleton, and membrane-all of which are highly sensitive to supraphysiological shear exposure. Given the need to minimise blood trauma within artificial organs, we observed RBC in supraphysiological shear through direct visualisation to gain understanding of processes leading to blood damage.
View Article and Find Full Text PDFRed blood cell (RBC) populations are inherently heterogeneous, given mature RBC lack the transcriptional machinery to re-synthesize proteins affected during in vivo aging. Clearance of older, less functional cells thus aids in maintaining consistent hemorheological properties. Scenarios occur, however, where portions of mechanically impaired RBC are re-introduced into blood (e.
View Article and Find Full Text PDFDespite technological advances in ventricular assist devices (VADs) to treat end-stage heart failure, hemocompatibility remains a constant concern, with supraphysiological shear stresses an unavoidable reality with clinical use. Given that impeller rotational speed is related to the instantaneous shear within the pump housing, it is plausible that the modulation of pump speed may regulate peak mechanical shear stresses and thus ameliorate blood damage. The present study investigated the hemocompatibility of the HeartWare HVAD in three configurations typical of clinical applications: standard systemic support left VAD (LVAD), pediatric support LVAD, and pulmonary support right VAD (RVAD) conditions.
View Article and Find Full Text PDFBlood is a non-Newtonian, shear-thinning fluid owing to the physical properties and behaviors of red blood cells (RBCs). Under increased shear flow, pre-existing clusters of cells disaggregate, orientate with flow, and deform. These essential processes enhance fluidity of blood, although accumulating evidence suggests that sublethal blood trauma-induced by supraphysiological shear exposure-paradoxically increases the deformability of RBCs when examined under low-shear conditions, despite obvious decrement of cellular deformation at moderate-to-higher shear stresses.
View Article and Find Full Text PDFBackground: Hemochromatosis (HH) is characterized by chronic iron accumulation, leading to deleterious effects to various organ systems. A common approach to managing iron load involves large-volume venesection. Some countries authorize HH venesections to be used in the development of transfusable blood products, although concerns remain regarding suitability.
View Article and Find Full Text PDFBackground: Individuals with hereditary hemochromatosis (HH) receive frequent blood withdrawals (ie, venesections) as part of their primary treatment to assist in normalizing blood iron levels. It remains unclear whether this source of blood is suitable for use in blood product development, as current data indicate that red blood cell (RBC) deformability, both before and after shear stress exposure, is impaired in individuals with HH, relative to healthy controls. Given that venesection therapy is known to significantly reduce circulating iron levels in individuals with HH, the current study examined whether venesection therapy is effective at improving RBC mechanical properties, both before and after shear stress exposure, in individuals with HH.
View Article and Find Full Text PDFBlood exposure to supraphysiological shear stress within mechanical circulatory support is suspected of reducing red blood cell (RBC) deformability and being primal in the pathogenesis of several secondary complications. No prior works have explored RBC dynamics with the resolution required to determine shear elastic modulus, and/or cell capillary velocity, following exposure to mechanical stresses. Healthy RBCs were exposed to 0, 5, 50, and 100 Pa in a Couette shearing system.
View Article and Find Full Text PDFIntroduction:: Accumulating evidence demonstrates that subhaemolytic mechanical stresses, typical of circulatory support, induce physical and biochemical changes to red blood cells. It remains unclear, however, whether cell age affects susceptibility to these mechanical forces. This study thus examined the sensitivity of density-fractionated red blood cells to sublethal mechanical stresses.
View Article and Find Full Text PDFCirculation of blood depends, in part, on the ability of red blood cells (RBCs) to aggregate, disaggregate, and deform. The primary intrinsic disaggregating force of RBCs is derived from their electronegativity, which is largely determined by sialylated glycoproteins on the plasma membrane. Given supraphysiological shear exposure - even at levels below those which induce hemolysis - alters cell morphology, we hypothesized that exposure to supraphysiological and subhemolytic shear would cleave membrane-bound sialic acid, altering the electrochemical and physical properties of RBCs, and thus increase RBC aggregation.
View Article and Find Full Text PDFHaemochromatosis remains the most prevalent genetic disorder of Caucasian populations in Australia and the United States, occurring in ∼1 of 200 individuals and having a carrier frequency of 10-14%. Hereditary haemochromatosis is an autosomal recessive condition, that is phenotypically characterised by a gradual accumulation of iron, above and beyond that required for biological function. Once the binding capacity of iron carriers reaches saturation, the highly reactive free iron generates radicals that may lead to widespread cellular dysfunction.
View Article and Find Full Text PDFPatients receiving mechanical circulatory support often present with heightened inflammation and free radical production associated with pre-existing conditions in addition to that which is due to blood interactions with nonbiological surfaces. The aim of this experimental laboratory study was to assess the deformability of red blood cells (RBC) previously exposed to oxygen free radicals and determine the susceptibility of these cells to mechanical forces. In the present study, RBC from 15 healthy donors were washed and incubated for 60 min at 37°C with 50 µM phenazine methosulfate (PMS; an agent that generates superoxide within RBC).
View Article and Find Full Text PDFClassic features of polycystic ovary syndrome (PCOS) include derangement of metabolic and cardiovascular health, and vascular dysfunction is commonly reported. These comorbidities indicate impaired blood flow; however, other than limited reports of increased plasma viscosity, surprisingly little is known regarding the physical properties of blood in PCOS. We aimed to investigate whether haemorheology was impaired in women with PCOS.
View Article and Find Full Text PDFIntroduction: Despite current generation mechanical assist devices being designed to limit shear stresses and minimise damage to formed elements in blood, severe secondary complications suggestive of impaired rheological functioning are still observed. At present, the precise interactions between the magnitude-duration of shear stress exposure and the deformability of red blood cells (RBC) remain largely undescribed for repeated subhaemolytic shear stress duty-cycles of less than 15 s. Given that the time taken for blood to traverse mechanical devices (e.
View Article and Find Full Text PDFIntroduction: Given the severity of the current imbalance between blood donor supply and recipient demand, discarded blood drawn from the routine venesections of haemochromatosis (HFE-HH) patients may serve as a valuable alternative source for blood banks and transfusion. We investigated whether functional or biochemical differences existed between HFE-HH and control blood samples, with particular focus upon the haemorheological properties, to investigate the viability of venesected blood being subsequently harvested for blood products.
Methods: Blood samples were collected from HFE-HH patients undergoing venesection treatment (n = 19) and healthy volunteers (n = 8).