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Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature.

Abstract

In sickle cell (SS) vaso-occlusion, the culminating event is blockage of blood vessels by sickled red blood cells (SS RBCs). As shown in animal models, SS RBC-induced vaso-occlusion is often partial, allowing for a residual flow, hence oxygen delivery to partially occluded vessels could reduce vaso-occlusion. The efficacy of an oxygenated perflubron-based fluorocarbon emulsion (PFE) was tested for its anti-vaso-occlusive effects in the ex vivo mesocecum vasculature of the rat. Microvascular obstruction was induced by the infusion of deoxygenated SS RBCs into ex vivo preparations with or without pretreatment with platelet-activating factor (PAF). PAF induced enhanced SS RBC-endothelium interactions, leading to greater vaso-occlusion. Microvascular blockage resulted in increased peripheral resistance units (PRU). Deoxygenated SS RBCs caused a persistent 1.5-fold PRU increase in untreated preparations and approximately a 2-fold PRU increase in PAF-treated preparations. The greater PRU in PAF-treated preparations was caused by widespread adhesion and postcapillary blockage. Oxygenated PFE, but not deoxygenated PFE, resulted in PRU decreases to baseline values in both groups of experiments (with or without PAF). The PRU decrease caused by oxygenated PFE infusion was caused by unsickling of SS RBCs in partially occluded vessels, with no antiadhesive effect on already adherent SS RBCs as assessed by intravital microscopy. PFE had no effect on vascular tone. The efficacy of PFE appears to result from its greater capacity to dissolve oxygen (10-fold higher than plasma). The dislodgement of trapped SS RBCs and an increase in wall shear rates will help reverse the partial obstruction. Thus, oxygenated PFE is capable of reducing SS RBC-induced vaso-occlusion, and further development of this approach is advisable.

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  • Authors+Show Affiliations

    ,

    Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. kaul@aecom.yu.edu

    ,

    Source

    Blood 98:10 2001 Nov 15 pg 3128-31

    MeSH

    Adult
    Anemia, Sickle Cell
    Animals
    Cecum
    Cell Adhesion
    Drug Carriers
    Drug Evaluation, Preclinical
    Emulsions
    Endothelium, Vascular
    Erythrocytes, Abnormal
    Fluorocarbons
    Humans
    Microcirculation
    Oxygen
    Perfusion
    Platelet Activating Factor
    Rats
    Solubility
    Vascular Resistance

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    11698300

    Citation

    Kaul, D K., et al. "Ameliorating Effects of Fluorocarbon Emulsion On Sickle Red Blood Cell-induced Obstruction in an Ex Vivo Vasculature." Blood, vol. 98, no. 10, 2001, pp. 3128-31.
    Kaul DK, Liu X, Nagel RL. Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature. Blood. 2001;98(10):3128-31.
    Kaul, D. K., Liu, X., & Nagel, R. L. (2001). Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature. Blood, 98(10), pp. 3128-31.
    Kaul DK, Liu X, Nagel RL. Ameliorating Effects of Fluorocarbon Emulsion On Sickle Red Blood Cell-induced Obstruction in an Ex Vivo Vasculature. Blood. 2001 Nov 15;98(10):3128-31. PubMed PMID: 11698300.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature. AU - Kaul,D K, AU - Liu,X, AU - Nagel,R L, PY - 2001/11/8/pubmed PY - 2002/1/5/medline PY - 2001/11/8/entrez SP - 3128 EP - 31 JF - Blood JO - Blood VL - 98 IS - 10 N2 - In sickle cell (SS) vaso-occlusion, the culminating event is blockage of blood vessels by sickled red blood cells (SS RBCs). As shown in animal models, SS RBC-induced vaso-occlusion is often partial, allowing for a residual flow, hence oxygen delivery to partially occluded vessels could reduce vaso-occlusion. The efficacy of an oxygenated perflubron-based fluorocarbon emulsion (PFE) was tested for its anti-vaso-occlusive effects in the ex vivo mesocecum vasculature of the rat. Microvascular obstruction was induced by the infusion of deoxygenated SS RBCs into ex vivo preparations with or without pretreatment with platelet-activating factor (PAF). PAF induced enhanced SS RBC-endothelium interactions, leading to greater vaso-occlusion. Microvascular blockage resulted in increased peripheral resistance units (PRU). Deoxygenated SS RBCs caused a persistent 1.5-fold PRU increase in untreated preparations and approximately a 2-fold PRU increase in PAF-treated preparations. The greater PRU in PAF-treated preparations was caused by widespread adhesion and postcapillary blockage. Oxygenated PFE, but not deoxygenated PFE, resulted in PRU decreases to baseline values in both groups of experiments (with or without PAF). The PRU decrease caused by oxygenated PFE infusion was caused by unsickling of SS RBCs in partially occluded vessels, with no antiadhesive effect on already adherent SS RBCs as assessed by intravital microscopy. PFE had no effect on vascular tone. The efficacy of PFE appears to result from its greater capacity to dissolve oxygen (10-fold higher than plasma). The dislodgement of trapped SS RBCs and an increase in wall shear rates will help reverse the partial obstruction. Thus, oxygenated PFE is capable of reducing SS RBC-induced vaso-occlusion, and further development of this approach is advisable. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/11698300/Ameliorating_effects_of_fluorocarbon_emulsion_on_sickle_red_blood_cell_induced_obstruction_in_an_ex_vivo_vasculature_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=11698300 DB - PRIME DP - Unbound Medicine ER -