In vivo demonstration of red cell-endothelial interaction, sickling and altered microvascular response to oxygen in the sickle transgenic mouse.

摘要: Intravascular sickling, red cell-endothelium interaction, and altered microvascular responses have been suggested to contribute the pathophysiology of human sickle cell disease, but never demonstrated under in vivo flow. To address this issue, we examined a transgenic mouse line, alphaHbetaSbetaS-Antilles [betaMDD] which has combined high (78%) expression beta S S-Antilles globins. In microcirculatory studies using cremaster muscle preparation showed adhesion cells, restricted postcapillary venules, mice not control mice. Electron microscopy revealed distinct contacts between membrane endothelium surface. Some cells exhibiting sickling were regularly observed venular Infusion into ex mesocecum vasculature also exclusively venules. Under resting conditions (pO2, 15-20 mmHg), there no differences diameters mice; however, drastic reduction velocities (Vrbc) with maximal Vrbc decrease (> 60%) occurring sites sickling. Local, transient hyperoxia 150 mmHg) resulted striking controls, oxygen caused 69% arteriolar constriction, accompanied by 75% Vrbc. contrast, mice, only 8% diameter 68% increase VrBC; latter is probably due an improved flow behavior as consequence unsickling. summary, hemoglobin results intravascular interaction. The response could be secondary blood rheological changes, although possible intrinsic endothelial cell/vascular smooth function may contribute. These serve useful model investigate vasoocclusive mechanisms, well test potential therapies.