Rheological Properties of Hemoglobin Vesicles (Artificial Oxygen Carriers) Suspended in a Series of Plasma-Substitute Solutions

Sakai, Hiromi; Sato, Atsushi; Takeoka, Shinji; Tsuchida, Eishun

doi:10.1021/la7004503

Cited by 33 publications

(65 citation statements)

References 63 publications

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“…The occupied volume fraction of liposome is nearly 40%, and the fluid shows a "shear-thinning" profile because the liposome flocculation reversibly dissociates at a higher shear rate. At the center of the tube, where the shear rate is the lowest, viscosity is extremely high because of the presence of fractal-structured flocculation of liposomes (22). The parabolic velocity profile in a tube would become slightly blunted because of the presence of the liposome flocculation (2), which increases the shear rate near the wall where the flocculation tends to be dissociated.…”

Section: Discussionmentioning

confidence: 99%

“…A high-concentration liposomal suspension was prepared from a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine, cholesterol, and 1,5-bis-O-hexadecyl-N-succinyl-L-glutamate in a molar ratio of 5:5:1 (Nippon Fine Chemical, Osaka, Japan) and 1,2-distearoylsn-glycero-3-phosphatidylethanolamine-N-poly(ethylene glycol) (0.3 mol% of the total lipid; NOF, Tokyo, Japan) (21,22). The particle size was regulated using an extrusion method and suspended in physiological saline; the resultant particle diameter was 279 Ϯ 95 nm.…”

Section: Preparation Of Suspending Solutions and Their Viscometric Anmentioning

confidence: 99%

“…The particle size was regulated using an extrusion method and suspended in physiological saline; the resultant particle diameter was 279 Ϯ 95 nm. The liposomes contained a concentrated human Hb solution (35 g/dl) (21,22). The resulting liposomal suspension was once ultracentrifuged (50,000 g, 30 min) and resuspended in 5% recombinant human serum albumin, obtained from Nipro.…”

Section: Preparation Of Suspending Solutions and Their Viscometric Anmentioning

confidence: 99%

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Peculiar flow patterns of RBCs suspended in viscous fluids and perfused through a narrow tube (25 μm)

Sakai¹,

Sato²,

Okuda³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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(RBCs) generally deform to adopt a parachute-like, torpedo-like, or other configuration to align and flow through a capillary that is narrower than their major axis. As described herein, even in a narrow tube (25 m) with diameter much larger than that of a capillary, flowing RBCs at 1 mm/s align axially and deform to a paraboloid shape in a viscous Newtonian fluid (505 kDa dextran medium) with viscosity of 23.4 -57.1 mPa ⅐ s. A high-speed digital camera image showed that the silhouette of the tip of RBCs fits a parabola, unlike the shape of RBCs in capillaries, because of the longer distance of the RBC-free layer between the tube wall and the RBC surface (ϳ8.8 m). However, when RBCs are suspended in a "non-Newtonian" viscous fluid (liposome-40 kDa dextran medium) with a shear-thinning profile, they migrate toward the tube wall to avoid the axial lining, as "near-wall-excess," which is usually observed for platelets. This migration results from the presence of flocculated liposomes at the tube center. In contrast, such near-wall excess was not observed when RBCs were suspended in a nearly Newtonian liposome-albumin medium. Such unusual flow patterns of RBCs would be explainable by the principle; a larger particle tends to flow near the centerline, and a small one tends to go to the wall to flow with least resistance. However, we visualized for the first time the complete axial aligning and near-wall excess of RBCs in the noncapillary size tube in some extreme conditions. hemorheology; erythrocytes; viscometry; artificial red cells; microcirculation RED BLOOD CELLS (RBCs) or erythrocytes in mammals lost their nuclei during their evolution and specialization for their role of oxygen transport. Microcirculatory observation of capillaries (Ͼ4 m diameter) that are narrower than the RBC diameter (8 m) revealed that flowing RBCs alter their own morphology from a biconcave disk to various configurations resembling a parachute, umbrella, jellyfish, or torpedo, as though they were alive (10,11,29). This phenomenon was first reported in the 1960s.During blood flow in a capillary, a pressure gradient exists: a pressure drop in the direction of flow. The higher pressure in the rear tends to compress the rear portion of the RBCs. In response to such stress, the elastic cellular structure of RBCs (biconcave disc) is known to be effective to deform and stir the intracellular viscous hemoglobin (Hb) solution (Ͼ35 g/dl), thereby facilitating gas exchange (1,6,14). From conventional microscopic observation of peripheral tissues, it is difficult to discern the capillary shape, especially at a reduced hematocrit resulting from the Fahraeus effect and plasma skimming, but we can infer the presence of functional capillary walls near the RBCs by the presence of deformed and aligned RBC flow (25,29). In glass tubes (inner diameter, Ͻ12 m), similar deformation of RBCs is apparent (8, 35). On the other hand, the glycocalyx layer of the capillary endothelium interacts with the plasma layer fluid and retards its flow. Its hydraulic resista...

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Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Suspending Solutions and Their Viscometric Anmentioning

confidence: 99%

Section: Preparation Of Suspending Solutions and Their Viscometric Anmentioning

confidence: 99%

See 1 more Smart Citation

Peculiar flow patterns of RBCs suspended in viscous fluids and perfused through a narrow tube (25 μm)

Sakai¹,

Sato²,

Okuda³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

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“…HbV must be delivered in solution in a plasma expander, thus allowing the design of its rheological properties. The rheology of HbV suspended in albumin was nearly Newtonian, whereas starch, dextran, and gelatin caused the suspensions to be non-Newtonian with shear-thinning behavior, as solution viscosity decreases as the applied shearing stress increased (131).…”

Section: Molecular Sizementioning

confidence: 99%

Examining and Mitigating Acellular Hemoglobin Vasoactivity

Cabrales

2013

Antioxidants & Redox Signaling

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Significance: There has been a striking advancement in our understanding of red cell substitutes over the past decade. Although regulatory oversight has influenced many aspects of product development in this period, those who have approached the demonstration of efficacy of red cell substitutes have failed to understand their implication at the level of the microcirculation, where blood interacts closely with tissue. Recent Advances: The understanding of the adverse effects of acellular hemoglobin (Hb)-based oxygen carriers (HBOCs) has fortunately expanded from Hb-induced renal toxicity to a more complete list of biochemical mechanism. In addition, various unexpected adverse reactions were seen in early clinical studies. The effects of the presence of acellular Hb in plasma are relatively unique because of the convergence of mechanical and biochemical natures. Critical Issues: Controlling the variables using genetic engineering and chemical modification to change specific characteristics of the Hb molecule may allow for solving the complex multivariate problems of acellular Hb vasoactivity. HBOCs may never be rendered free of negative effects; however, quantifying the nature and extent of microvascular complications establishes a platform for designing new ameliorative therapies. Future Directions: It is time to leave behind the study of vasoactivity and toxicity based on bench-top measurements of biochemical changes and those based solely on systemic parameters in vivo, and move to a more holistic analysis of the mechanisms creating the problems, complemented with meaningful studies of efficacy. Antioxid. Redox Signal. 18, 2329-2341.

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“…These factors also cause blood to be shear-thinning, whereby its viscosity decreases as the shear rate increases. 75 Blood shear thinning properties redistribute shear rate dependent energy expenditure from the bulk of the flow (RBC core) to the periphery (CFL), increasing WSS. This effect is in part counteracted by the increase in CFL width.…”

Section: Blood Rheology and Plasma Expansionmentioning

confidence: 99%

Blood Substitutes

Cabrales¹,

Intaglietta²

2013

ASAIO Journal

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The development of oxygen (O2) carrying blood substitutes has evolved from the goal of replicating blood O2 transports properties to that of preserving microvascular and organ function, reducing the inherent or potential toxicity of the material used to carry O2, and treating pathologies initiated by anemia and hypoxia. Furthermore, the emphasis has shifted from blood replacement fluid to “O2 therapeutics” that restore tissue oxygenation to specific tissues regions. This review covers the different alternatives, potential and limitations of hemoglobin based O2 carriers (HBOCs) and perfluorocarbon based O2 carriers (PFCOCs), with emphasis on the physiological conditions disturbed in the situation that they will be used. It describes how concepts learned from plasma expanders without O2 carrying capacity can be applied to maintain O2 delivery and summarizes the microvascular responses due to HBOCs and PFCOCs. This review also presents alternative applications of HBOCs and PFCOCs namely: 1) How HBOC O2 affinity can be engineered to target O2 delivery to hypoxic tissues; and 2) How the high gas solubility of PFCOCs provides new opportunities for carrying, dissolving and delivering gases with biological activity. It is concluded that current blood substitutes development has amplified their applications horizon by devising therapeutic functions for oxygen carriers requiring limited O2 delivery capacity restoration. Conversely, full, blood-like O2 carrying capacity re-establishment awaits control of O2 carrier toxicity.

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Rheological Properties of Hemoglobin Vesicles (Artificial Oxygen Carriers) Suspended in a Series of Plasma-Substitute Solutions

Cited by 33 publications

References 63 publications

Peculiar flow patterns of RBCs suspended in viscous fluids and perfused through a narrow tube (25 μm)

Peculiar flow patterns of RBCs suspended in viscous fluids and perfused through a narrow tube (25 μm)

Examining and Mitigating Acellular Hemoglobin Vasoactivity

Blood Substitutes

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