Biphasic impairment of erythrocyte deformability in response to repeated, short duration exposures of supraphysiological, subhaemolytic shear stress

McNamee, Antony P.; Tansley, Geoff; Sabapathy, Surendran; Simmonds, Michael J.

doi:10.3233/bir-15108

Cited by 23 publications

(34 citation statements)

References 27 publications

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“…Furthermore, we carefully monitored maximal areal deformations of the lipid bilayer during these processes and note that even under extreme conditions, such as the case of Figure 6 , they were only ~1−2%; this is significantly smaller than the approximate areal strain of 10% a cell can sustain under dynamic (i.e., impact) conditions (Li et al, 2013 ). It is also at, or below, the somewhat lower values in the range 2–3% found under different deformation conditions (Leverett et al, 1972 ; Sandza et al, 1974 ; Sutera and Mehrjardi, 1975 ; Evans et al, 1976 ; Sutera et al, 1977 ; Daily et al, 1984 ; Watanabe et al, 2006 ; Wantanbe et al, 2007 ; Meram et al, 2013 ; Hashimoto, 2014 ; McNamee et al, 2016 ; Horobib et al, 2017 ). We thus conclude that pressure-induced cell bursting due to large area deformation of the bilayer is not likely to occur in these conditions as discussed further in section 4.5 along with additional detail and perspective.…”

Section: Overview Of the Simulation Model And Resultsmentioning

confidence: 87%

Erythrocyte Aging, Protection via Vesiculation: An Analysis Methodology via Oscillatory Flow

2018

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We demonstrate that erythrocyte deformations, specifically of a type as occur in splenic flow (Zhu et al., 2017), and of the type that promote vesiculation can be caused by simple, yet tailored, oscillatory shear flow. We show that such oscillatory shear flow provides an ideal environment to explore a wide variety of metabolic and biochemical effects that promote erythrocyte vesiculation. Deformation details, typical of splenic flow, such as in-folding and implications for membrane/skeleton interaction are demonstrated and quantitatively analyzed. We introduce a theoretical, essentially analytical, vesiculation model that directly couples to our more complex numerical, multilevel, model that clearly delineates various fundamental elements, i.e., sub-processes, that are involved and mediate the vesiculation process. This analytical model highlights particulary important vesiculation precursors such as areas of membrane/skeleton disruptions that trigger the vesiculation process. We demonstrate, using flow cytometry, that the deformations we experimentally induce on cells, and numerically simulate, do not induce lethal forms of cell damage but do induce vesiculation as theoretically forecasted. This, we demonstrate, provides a direct link to cell membrane/skeletal damage such as is associated with metabolic and aging damage. An additional noteworthy feature of this approach is the avoidance of artificial devices, e.g., micro-fluidic chambers, in which deformations and their time scales are often unrepresentative of physiological processes such as splenic flow.

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Section: Overview Of the Simulation Model And Resultsmentioning

confidence: 87%

Erythrocyte Aging, Protection via Vesiculation: An Analysis Methodology via Oscillatory Flow

2018

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“…Given impairments in RBC deformability lead to detrimental functional implications, including the diminished regulation of microcirculatory blood flow and the precipitation of complete cell destruction (8,16), an index of RBC susceptibility to mechanical damage was expressed by calculating the differences in SS 1/2 :EI max relative to control measures (prior to shearing), as a percentage of the control value (22,24):…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress Increases Erythrocyte Sensitivity to Shear‐Mediated Damage

et al. 2017

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Patients 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). Incubated RBC and negative controls were assessed for their deformability and susceptibility to mechanical damage (using ektacytometry) prior to the application of shear stress, and also following exposure to 25 different shear conditions of varied magnitudes (shear stress 1, 4, 16, 32, 64 Pa) and durations (1, 4, 16, 32, 64 s). The salient findings demonstrate that incubation with PMS impaired important indices of RBC deformability indicating altered cell mechanics by ∼19% in all conditions (pre- and postexposure to shear stress). The typical trends in shear-mediated changes in RBC susceptibility to mechanical damage, following conditioning shear stresses, were maintained for PMS incubated and control conditions. We demonstrated that free radicals hinder the ability of RBC to deform; however, RBC retained their typical mechanical response to shear stress, albeit at a decreased level compared with control following exposure to PMS. Our findings also indicate that low shear exposure may decrease cell sensitivity to mechanical damage upon subsequent shear stress exposures. As patients receiving mechanical circulatory support have elevated exposure to free radicals (which limits RBC deformability), concomitant exposure to high shear environments needs to be minimized.

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“…The impact of shear removal of membrane-bound sialic acid content may also explain the decreased RBC deformability and increased membrane rigidity observed in other studies (Horobin et al, 2017;McNamee et al, 2017;McNamee et al, 2016b;Simmonds et al, 2014;Simmonds and Meiselman, 2017). As sialic acid is negatively ionized, and cytosolic hemoglobin is positively charged, membrane-bound sialic acid is proposed to be an important regulator of hemoglobin distribution in the cytoplasm, thus also playing a role in maintaining the oxygen carrying capacity of RBCs (Huang et al, 2016).…”

Section: Accepted Manuscriptmentioning

confidence: 88%

“…complications have been reported with long-term use that are suggestive of blood damage and malfunction, without remarkable hemolysis. This damage, which is due to bloodinteraction with non-physiological environments (i.e., contact with foreign surfaces, elevated shear forces, turbulence and cavitation), can cause dangerous complications of altered perfusion and rheological properties of blood (Horobin et al, 2017;McNamee et al, 2017;McNamee et al, 2016b;Ruggeri et al, 2006). The observed complications of hemorrhagic events, thrombotic events, tissue ischemia and anemia, leading to multi-system organ failure (Kirklin et al, 2014), may be partially explained by altered RBC aggregation behavior.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…One of the primary contributors to the negative charge of the RBC is the abundant distribution of sialic acid across the cell surface (Eylar et al, 1962), accounting for ~90% of the cell's net negative charge and hydrophobicity (Mehdi et al, 2012). High shear environments have been reported to induce ultrastructural changes to RBCs, causing changed morphology (McNamee et al, 2016b), cell fragmentation (Watanabe et al, 2007), and disruption of the lipid bilayer (Dao et al, 1993). Given the significant surface alterations that occur to the cell membrane of RBCs with subhemolytic trauma, it is likely that supraphysiological shear stress cleaved sialic acid from the cell membrane, decreasing the electrostatic surface charge and thus also the disaggregating force intrinsic to the glycocalyx.…”

Section: Electrophoretic Mobility and Zeta Potentialmentioning

confidence: 99%

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Sublethal mechanical trauma alters the electrochemical properties and increases aggregation of erythrocytes

McNamee

Tansley

Simmonds

2018

Microvascular Research

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Circulation 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. Isolated RBCs from healthy donors (n = 20) were suspended in polyvinylpyrrolidinone. Using a Poiseuille shearing system, RBC suspensions were exposed to 125 Pa for 1.5 s for three duty-cycles. Following the first and third shear duty-cycle, samples were assessed for: RBC aggregation; the ability of RBCs to aggregate independent of plasma ("aggregability"); disaggregation shear rate; membrane-bound sialic acid content, and; cell electrophoretic mobility. Initial shear exposure significantly increased RBC aggregation, aggregability, and the shear required for rouleaux dispersion. Sialic acid concentration significantly decreased on isolated RBC membranes ghosts, and increased in the supernatant following shear. Initial shear exposure decreased the electrophoretic mobility of RBCs, decreasing the electronegative charge from -15.78 ± 0.31 to -7.55 ± 0.21 mV. Three exposures to the shear duty-cycle did not further compound altered RBC measures. A single exposure to supraphysiological and subhemolytic shear significantly decreased the electrochemical charge of the RBC membrane, concurrently increasing cell aggregation/aggregability. The cascading implications of hyperaggregation appears to potentially explain the ischemia-associated complications commonly reported following mechanical circulatory support.

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Biphasic impairment of erythrocyte deformability in response to repeated, short duration exposures of supraphysiological, subhaemolytic shear stress

Abstract: Repeat applications of short duration supraphysiological, subhaemolytic shear stress induces a biphasic RBC deformability response that appears to progressively improve initially impaired RBC populations.

Cited by 23 publications

References 27 publications

Erythrocyte Aging, Protection via Vesiculation: An Analysis Methodology via Oscillatory Flow

Erythrocyte Aging, Protection via Vesiculation: An Analysis Methodology via Oscillatory Flow

Oxidative Stress Increases Erythrocyte Sensitivity to Shear‐Mediated Damage

Sublethal mechanical trauma alters the electrochemical properties and increases aggregation of erythrocytes

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