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 bl ood 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 f low, hence oxygen delivery to partially occluded vessels could reduce vaso- occlusion. The efficacy of an oxygenated perflubron-based fluorocarbon emul sion (PFE) was tested for its anti-vaso-occlusive effects in the ex vivo me socecum vasculature of the rat. Microvascular obstruction was induced by th e infusion of deoxygenated SS RBCs into ex vivo preparations with or withou t pretreatment with platelet-activating factor (PAF). PAF induced enhanced SS RBC-endothelium interactions, leading to greater vaso-occlusion. Microva scular blockage resulted in increased peripheral resistance units (PRU). De oxygenated SS RBCs caused a persistent 1.5-fold PRU increase in untreated p reparations and approximately a 2-fold PRU increase in PAF-treated preparat ions. The greater PRU in PAF-treated preparations was caused by widespread adhesion and postcapillary blockage. Oxygenated PFE, but not deoxygenated P FE, resulted in PRU decreases to baseline values in both groups of experime nts (with or without PAF). The PRU decrease caused by oxygenated PFE infusi on was caused by un-sickling of SS RBCs in partially occluded vessels, with no antiadhesive effect on already adherent SS RBCs as assessed by intravit al microscopy. PFE had no effect on vascular tone. The efficacy of PFE appe ars 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 s hear rates will help reverse the partial obstruction. Thus, oxygenated PFE is capable of reducing SS RBC-induced vaso-occlusion, and further developme nt of this approach is advisable. (C) 2001 by The American Society of Hemat ology.