Intravital microscopy of capillary hemodynamics in sickle cell disease.

Lipowsky, Herbert H.; Sheikh, N U; Katz, D M

doi:10.1172/jci113036

Cited by 99 publications

(79 citation statements)

References 23 publications

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“…RBC deformability was measured by using a laser-assisted optical rotational cell analyzer (LORCA) as described in SI Methods and previously (45,46). A priori, we defined two main levels of shear stress, 3 and 30 Pa (49), with 3 Pa representing a clinically relevant level of shear stress in the microcirculation (47,48). Cytokine assays.…”

Section: Methodsmentioning

confidence: 99%

“…We measured RBC deformability using the laser-assisted optical rotational cell analyzer (LORCA) assay, in which RBCs are subjected to increasing shear stress over several minutes (45,46). Our prespecified major shear stress of interest was 3 Pa, a level that may be encountered in the microcirculation of humans (47)(48)(49). Deformability also decreased significantly over the 42-day storage period at 30 Pa, suggesting that the membrane defect induced by storage is pronounced enough to moderately resist the ability to deform even at a very high level of shear stress.…”

Section: H) P Values Represent Comparison Between Values In Rbcs Assmentioning

confidence: 99%

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Evolution of adverse changes in stored RBCs

Bennett‐Guerrero¹,

Veldman²,

Doctor

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

552

556

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Recent studies have underscored questions about the balance of risk and benefit of RBC transfusion. A better understanding of the nature and timing of molecular and functional changes in stored RBCs may provide strategies to improve the balance of benefit and risk of RBC transfusion. We analyzed changes occurring during RBC storage focusing on RBC deformability, RBC-dependent vasoregulatory function, and S-nitrosohemoglobin (SNO-Hb), through which hemoglobin (Hb) O2 desaturation is coupled to regional increases in blood flow in vivo (hypoxic vasodilation). Five hundred ml of blood from each of 15 healthy volunteers was processed into leukofiltered, additive solution 3-exposed RBCs and stored at 1-6°C according to AABB standards. Blood was subjected to 26 assays at 0, 3, 8, 24 and 96 h, and at 1, 2, 3, 4, and 6 weeks. RBC SNO-Hb decreased rapidly (1.2 ؋ 10 ؊4 at 3 h vs. 6.5 ؋ 10 ؊4 (fresh) mol S-nitrosothiol (SNO)/mol Hb tetramer (P ‫؍‬ 0.032, mercuric-displaced photolysis-chemiluminescence assay), and remained low over the 42-day period. The decline was corroborated by using the carbon monoxide-saturated copper-cysteine assay [3.0 ؋ 10 ؊5 at 3 h vs. 9.0 ؋ 10 ؊5 (fresh) mol SNO/mol Hb]. In parallel, vasodilation by stored RBCs was significantly depressed. RBC deformability assayed at a physiological shear stress decreased gradually over the 42-day period (P < 0.001). Time courses vary for several storage-induced defects that might account for recent observations linking blood transfusion with adverse outcomes. Of clinical concern is that SNO levels, and their physiological correlate, RBC-dependent vasodilation, become depressed soon after collection, suggesting that even ''fresh'' blood may have developed adverse biological characteristics.adenosine triphosphate ͉ hemoglobin ͉ nitric oxide ͉ S-nitrosothiols ͉ transfusion

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Section: Methodsmentioning

confidence: 99%

Section: H) P Values Represent Comparison Between Values In Rbcs Assmentioning

confidence: 99%

Evolution of adverse changes in stored RBCs

Bennett‐Guerrero¹,

Veldman²,

Doctor

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

552

556

View full text Add to dashboard Cite

show abstract

“…13 The relevance of both types of adhesion is suggested by in vivo observations of laminar, intermittent, and antegraderetrograde flow in the microvasculature of sickle cell subjects and sickle cell mouse models. [14][15][16] Initial events likely involve the adhesion of sickle erythrocytes to activated endothelial cells under laminar flow. The resultant adhesion of cells to the vascular wall creates nonlaminar and arrested flow, which propagates vascular occlusion by both static and flow adhesion mechanisms.…”

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confidence: 99%

Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin

Matsui

Varki

Embury

2002

Blood

115

110

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The adhesion of sickle erythrocytes to vascular endothelium is important to the generation of vascular occlusion. Interactions between sickle cells and the endothelium use several cell adhesion molecules. We have reported that sickle cell adhesion to endothelial cells under static conditions involves P-selectin. Others have shown that sickle cell adhesion is decreased by unfractionated heparin, but the molecular target of this inhibition has not been defined. We postulated that the adhesion of sickle cells to P-selectin might be the pathway blocked by unfractionated heparin. In this report we demonstrate that the flow adherence of sickle cells to thrombin-treated human vascular endothelial cells also uses P-selectin and that this component of adhesion is inhibited by unfractionated heparin. We also demonstrate that sickle cells adhere to immobilized recombinant P-selectin under flow conditions. This adhesion too was inhibited by unfractionated heparin, in a concentration range that is clinically attainable. These findings and the general role of P-selectin in initiating adhesion of blood cells to the endothelium suggest that unfractionated heparin may be useful in preventing IntroductionVascular occlusion is responsible for much of the morbidity associated with sickle cell disease. 1,2 Although the underlying cause of sickle cell disease is a single nucleotide mutation that directs the production of an easily polymerized hemoglobin protein, 3,4 both the erythrocyte sickling caused by hemoglobin polymerization and the interactions between a proadhesive population of sickle cells and the vascular endothelium are essential to vascular occlusion. 5,6 The correlation between sickle cell adhesiveness and the severity of vascular occlusion 7 led to extensive studies of the molecular mechanisms of adhesion. These pathways recently have been reviewed [8][9][10][11][12] and are briefly described here. Sickle red cells express adhesion molecules including integrin ␣ 4 ␤ 1 , CD36, band 3 protein, sulfated glycolipid, Lutheran protein, phosphatidylserine, and integrin-associated protein. The proadhesive sickle cells may bind to endothelial cell P-selectin, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), CD36, and integrins. Activation of endothelial cells by specific agonists enhances adhesion by inducing the expression of cellular adhesion molecules and by causing cell contraction, which exposes extracellular matrix proteins, such as thrombospondin (TSP), laminin, and fibronectin. Bridging molecules from the plasma such as von Willebrand factor (VWF) and TSP also participate in certain of these adhesive interactions.Sickle cell adhesion has been studied under both static and flow conditions. 13 The relevance of both types of adhesion is suggested by in vivo observations of laminar, intermittent, and antegraderetrograde flow in the microvasculature of sickle cell subjects and sickle cell mouse models. [14][15][16] Initial events likely involve the adhesion of sickle erythrocytes to activated endothelial cells under ...

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“…PIV is not restricted to optically acquired images only; US imaging has been used to measure the velocity distribution in the porcine left ventricle [4], with reported spatial and temporal resolutions of 0.4 mm and 0.5 ms, respectively [420]. In addition, X-ray velocimetry has been suggested as a Figure 31 Illustration of television microscopy methods of capillary velocity estimation [408].…”

Section: Particle Tracking Velocimetrymentioning

confidence: 99%

‘Go with the flow ’: A review of methods and advancements in blood flow imaging

Daly

Leahy

2012

Journal of Biophotonics

110

108

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Physics has delivered extraordinary developments in almost every facet of modern life. From the humble thermometer and stethoscope to X‐Ray, CT, MRI, ultrasound, PET and radiotherapy, our health has been transformed by these advances yielding both morphological and functional metrics. Recently high resolution label‐free imaging of the microcirculation at clinically relevant depths has become available in the research domain. In this paper, we present a comprehensive review on current imaging techniques, state‐of‐the‐art advancements and applications, and general perspectives on the prospects for these modalities in the clinical realm. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

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Intravital microscopy of capillary hemodynamics in sickle cell disease.

Cited by 99 publications

References 23 publications

Evolution of adverse changes in stored RBCs

Evolution of adverse changes in stored RBCs

Heparin inhibits the flow adhesion of sickle red blood cells to P-selectin

‘Go with the flow ’: A review of methods and advancements in blood flow imaging

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