Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature.
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.
Kaul
D K
DK
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. kaul@aecom.yu.edu
Liu
X
X
Nagel
R L
RL
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000188:drug therapy; D000818:Animals; D002432:Cecum / Q000098:blood supply; D002448:Cell Adhesion / Q000187:drug effects; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D004655:Emulsions; D004730:Endothelium, Vascular / Q000166:cytology; D004913:Erythrocytes, Abnormal / Q000187:drug effects / Q000473:pathology; D005466:Fluorocarbons / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006842:Hydrocarbons, Brominated; D008833:Microcirculation / Q000187:drug effects*; D010100:Oxygen / Q000008:administration & dosage* / Q000097:blood; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D012995:Solubility; D014655:Vascular Resistance / Q000187:drug effects
D004337:Drug Carriers; D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D010972:Platelet Activating Factor; C003072:perflubron; D010100:Oxygen