Extracellular fluid tonicity impacts sickle red blood cell deformability and adhesion
Extracellular fluid tonicity impacts sickle red blood cell deformability and adhesion
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DOI：
10.1182/blood-2017-04-780635
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发表时间：
2017-12-14
期刊：
影响因子：
20.3
通讯作者：
Lam, Wilbur A.
中科院分区：
文献类型：
--
作者：
Carden, Marcus A.;Fay, Meredith E.;Lam, Wilbur A.
异常镰状红细胞（sRBC）生物力学，包括病理变形性和粘附性，与镰状细胞病（SCD）的临床严重程度相关。在治疗血管闭塞性疼痛发作（VOE）（SCD发病的主要原因）期间，经常使用各种张力的临床静脉内液体（IVF）。然而，缺乏循证指南，并且对于在VOE期间使用哪些IVF没有共识。此外，尚不清楚IVF如何改变细胞外液张力，影响微循环中的sRBC生物力学，其中发生血管闭塞。在这里，我们报告了如何通过利用新型微循环体外微流体模型来改变临床IVF混合物的细胞外液张力，从而影响sRBC的生物力学特性，其中包括能够对sRBC环境进行脱氧以监测微通道阻塞风险变化的1个模型和一个“内皮化”微血管模型，该模型可测量毛细血管后微静脉条件下sRBC/内皮粘附的变化。具有较高张力的混合物（钠5 141 mEq/L）通过降低sRBC变形性、增加常氧和缺氧条件下的sRBC闭塞以及增加我们的微流体人类微血管模型中的sRBC粘附来影响sRBC生物力学。与过度低渗（钠= 103 mEq/L）的混合物，相反，减少sRBC粘附，但过度肿胀延长sRBC在毛细血管大小的微通道的通过时间。具有中等张力（钠= 111-122 mEq/L）的混合物导致sRBC生物力学的最佳变化，从而降低了我们模型中血管闭塞的风险。这些结果对SCD患者具有重要的转化意义，并保证了一项大规模的前瞻性临床研究，以解决SCD VOE期间的最佳IVF管理。
Abnormal sickle red blood cell (sRBC) biomechanics, including pathological deformability and adhesion, correlate with clinical severity in sickle cell disease (SCD). Clinical intravenous fluids (IVFs) of various tonicities are often used during treatment of vasoocclusive pain episodes (VOE), the major cause of morbidity in SCD. However, evidence-based guidelines are lacking, and there is no consensus regarding which IVFs to use during VOE. Further, it is unknown how altering extracellular fluid tonicity with IVFs affects sRBC biomechanics in the microcirculation, where vaso-occlusion takes place. Here, we report how altering extracellular fluid tonicity with admixtures of clinical IVFs affects sRBC biomechanical properties by leveraging novel in vitro microfluidic models of the microcirculation, including 1 capable of deoxygenating the sRBC environment to monitor changes in microchannel occlusion risk and an "endothelialized" microvascular model that measures alterations in sRBC/endothelium adhesion under postcapillary venular conditions. Admixtures with higher tonicities (sodium 5 141 mEq/L) affected sRBC biomechanics by decreasing sRBC deformability, increasing sRBC occlusion under normoxic and hypoxic conditions, and increasing sRBC adhesion in our microfluidic human microvasculature models. Admixtures with excessive hypotonicity (sodium = 103 mEq/L), in contrast, decreasedsRBC adhesion, but overswelling prolonged sRBC transit times in capillary-sized microchannels. Admixtures with intermediate tonicities (sodium = 111-122 mEq/L) resulted in optimal changes in sRBC biomechanics, thereby reducing the risk for vaso-occlusion in our models. These results have significant translational implications for patients with SCD and warrant a large-scale prospective clinical study addressing optimal IVF management during VOE in SCD.