MICROVASCULAR FUNCTION IN SICKLE CELL DISEASE

这项拟议的研究旨在阐明红细胞的动力学 镰状细胞病患者毛细血管(RBC)的隔离 (SCD)。基本方法是使用非侵入性的甲皱技术 显微镜观察红血球在皮肤毛细血管中的转运 指甲底部。录像带将由毛细血管在 SCD患者处于稳定期(无危象)和脉管期- 闭塞危机。这些录音将被数字化并进行分析以 测定安静状态下的红细胞速度(V RBC) 阻断反应后充血(PORH)激发试验。The PRH 会因血液流动停止一分钟而诱发 近指周围的压力袖带充气。在发病期间 由咬合引起的停滞，以及在较短的时间内 此外，还将分析V-RBC的瞬时减少 获取红细胞在皮肤中蓄积的定量指标 毛细血管开始停滞。初步研究有助于 制定一个累积指数，表示 RBC流量流入毛细血管，该毛细血管在 毛细血管；AI显示随着切变的减少而显著增加 低于过渡值YT的速率(Y)，并显示对于HbSS 被试的AI和Y-T在稳态时显著增加(与 到正常的HbAA对象)，并进一步增加交易危机，假设 由于红细胞与内皮细胞的粘附性增强。因此，拟议的研究 将寻找这些参数与发生和频率的相关性 在个体的危机中，红细胞的大小和变形性 各种血红蛋白疾病(如HbSSα-地中海贫血)和血浆水平 可溶性黏附分子ICAM-1，VCAM-1已被证明是 与红细胞-内皮细胞黏附增强相关。此外，RBC 甲皱的动态将与全身白细胞计数相关 和黏附分子I-CAM和V-CAM的循环水平，L- 选择素、P-选择素和E-选择素。HbSS和其他红细胞的变形性 将获得与甲皱显微镜研究相关的数据 通过测试它们通过5微米直径的毛孔的体外过滤能力 核孔过滤器。预计这些研究的结果 将为指导临床管理提供新的有用信息 SCD.

The proposed studies aims to elucidate the dynamics of red blood cell (RBC) sequestration in capillaries of patients with sickle cell disease (SCD). The basic approach is to use the non-invasive technique of nailfold microscopy to observe the transit of RBCs through skin capillaries at the base of the fingernail. Video recordings will be made of capillaries in patients with SCD during periods of steady state (crisis free) and vaso- occlusive crisis. These recordings will be digitized and analyzed to obtain red blood cell velocity (V RBC) in the resting state during the provocation test of post-occlusive reaction hyperemia (PORH). The PORH will be induced by cessation of blood flow for period of one minute by inflation of a pressure cuff around the proximal digit. During the onset of stasis induced by the occlusion, and during shorter periods of occlusion as well, the transient reductions in V RBC will be analyzed to obtain quantitative indices of accumulation of RBCs in the skin capillaries with the onset of stasis. Preliminary studies have served to formulate an accumulation index (AI) that represents the percentage of the RBC flux flowing into a capillary that becomes sequestered in the capillary; AI show shown to increase dramatically with reductions in shear rate (Y) below a transition value, YT and it was shown that for HbSS subjects, AI and Y T are significantly increased in steady state (compared to normal HbAA subjects) and increase further dealing crisis, presumable due to enhanced RBC to endothelium adhesion. Thus the proposed studies will seek correlates of these parameters with the occurrence and frequency of crisis in individual subjects, the size and deformability of RBCs of various hemoglobinopathies (e.g. HbSS alpha-thalassemia) and plasma levels of soluble adhesion molecule ICAM-1, VCAM-1 that have been shown to be correlated with enhanced RBC-endothelium adhesion. In addition, RBC dynamics in the nailfold will be correlated with systemic leukocyte count and circulating levels of the adhesion molecules I-CAM and V-CAM, L- selectin, P-selectin and E-selectin. Deformability of HbSS and other RBCs will be obtained for correlation with the studies of nailfold microscopy by examining their in vitro filterability through the 5mum diameter pores of Nuclepore filters. It is anticipated that the results of these studies will provide new and useful information to guide the clinical management of SCD.