Biorheology Research Laboratory, Menzies Health Institute Queensland, QLD, Australia.
Biorheology Research Laboratory, Menzies Health Institute Queensland, QLD, Australia.
Microvasc Res. 2022 Jan;139:104261. doi: 10.1016/j.mvr.2021.104261. Epub 2021 Oct 6.
Red blood cell (RBC) populations are inherently heterogeneous, given mature RBC lack the transcriptional machinery to re-synthesize proteins affected during in vivo aging. Clearance of older, less functional cells thus aids in maintaining consistent hemorheological properties. Scenarios occur, however, where portions of mechanically impaired RBC are re-introduced into blood (e.g., damaged from circulatory support, blood transfusion) and may alter whole blood fluid behavior. Given such perturbations are associated with poor clinical outcomes, determining the tolerable level of abnormal RBC in blood is valuable. Thus, the current study aimed to define the critical threshold of blood fluid properties to re-infused physically-impaired RBC. Cell mechanics of RBC were impaired through membrane cross-linking (glutaraldehyde) or intracellular oxidation (phenazine methosulfate). Mechanically impaired RBC were progressively re-introduced into the native cell population. Negative alterations of cellular deformability and high shear blood viscosity were observed following additions of only 1-5% rigidified RBC. Low-shear blood viscosity was conversely decreased following addition of glutaraldehyde-treated cells; high-resolution microscopy of these mixed cell populations revealed decreased capacity to form reversible aggregates and decreased aggregate size. Mixed RBC populations, when exposed to supraphysiological shear, presented with compounded mechanical impairment. Collectively, key determinants of blood flow behavior are sensitive to mechanical perturbations in RBC, even when only 1-5% of the cell population is affected. Given this fraction is well-below the volume of rigidified RBC introduced during circulatory support or transfusion practice, it is plausible that some adverse events following surgery and/or transfusion may be related to impaired blood fluidity.
红细胞（RBC）群体本质上是异质的，因为成熟的 RBC 缺乏转录机制来重新合成体内衰老过程中受影响的蛋白质。清除较老、功能较低的细胞有助于维持一致的血液流变学特性。然而，在某些情况下，部分机械损伤的 RBC 会重新进入血液（例如，循环支持、输血受损），并可能改变全血的流动行为。鉴于这些干扰与不良临床结局相关，确定血液中异常 RBC 的可接受水平是有价值的。因此，本研究旨在确定再输注物理损伤 RBC 时血液流体特性的临界阈值。通过膜交联（戊二醛）或细胞内氧化（吩嗪甲硫酸盐）来损伤 RBC 的细胞力学。逐渐将机械损伤的 RBC 重新引入到天然细胞群体中。仅添加 1-5%刚性 RBC 后，就观察到细胞变形性和高剪切血液粘度的负性改变。相反，添加戊二醛处理的细胞后低剪切血液粘度降低；对这些混合细胞群体进行高分辨率显微镜检查显示出可逆聚集能力降低和聚集物尺寸减小。当混合 RBC 群体暴露于超生理剪切力下时，会出现复合机械损伤。总之，血液流动行为的关键决定因素对 RBC 的机械扰动很敏感，即使只有 1-5%的细胞群体受到影响。鉴于在循环支持或输血实践中引入的刚性 RBC 体积远低于该分数，因此，手术后和/或输血后发生的一些不良事件可能与血液流动性受损有关。
