Hemolysis in sickle cell disease (SCD) releases cell free hemoglobin, which scavenges nitric oxide (NO), leading to pulmonary vascular vasoconstriction, increased pulmonary vascular resistance (PVR), and the development of PH. However, PVR is only one component of right ventricular (RV) afterload. Whether sickled red blood cells increase the total RV afterload, including compliance and wave reflections, is unclear. Patients with SCD and pulmonary hypertension (PH) have a significantly increased risk of sudden death compared to patients with SCD alone. Sickled red blood cells (RBCs) are fragile and lyse easily. Here, we sought to determine the acute effects of SCD RBCs and increased cell free hemoglobin on RV afterload. Main pulmonary artery pressures and flows were measured in C57BL6 mice before and after exchanges of whole blood (~200 uL, Hct = 45%) with an equal volume of SCD RBCs in plasma (Hct = 45%) or cell free hemoglobin (Hb+) in solution. After transfusions, animals were additionally stressed with acute hypoxia (AH; 10% O2). SCD RBCs increased PVR only compared to control RBCs; cell free hemoglobin increased PVR and wave reflections. These increases in RV afterload increased further with AH. The release of cell free hemoglobin from fragile SCD RBCs in vivo increases the total RV afterload and may impair RV function more than the SCD RBCs themselves.

中文翻译：

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红细胞镰状化对体内右心室后负荷的影响

镰状细胞病 (SCD) 中的溶血释放细胞游离血红蛋白，清除一氧化氮 (NO)，导致肺血管收缩、肺血管阻力 (PVR) 增加和肺动脉高压 (PH) 的发生。然而，PVR 只是右心室 (RV) 后负荷的组成部分之一。镰状红细胞是否会增加总右心室后负荷（包括顺应性和波反射）尚不清楚。与单纯 SCD 患者相比，SCD 合并肺动脉高压 (PH) 患者猝死的风险显着增加。镰状红细胞 (RBC) 很脆弱，很容易裂解。在这里，我们试图确定 SCD 红细胞和增加的无细胞血红蛋白对 RV 后负荷的急性影响。在将全血（~200 uL，Hct = 45%）与血浆中等体积的 SCD RBC（Hct = 45%）或无细胞血红蛋白（Hb+）交换之前和之后，测量 C57BL6 小鼠的主肺动脉压力和流量在溶液中。输血后，动物还承受急性缺氧（AH；10% O2）的压力。与对照红细胞相比，SCD 红细胞仅增加了 PVR；无细胞血红蛋白增加 PVR 和波反射。RV 后负荷的增加随着 AH 的增加而进一步增加。体内脆弱的 SCD RBC 释放的无细胞血红蛋白增加了总 RV 后负荷，并且可能比 SCD RBC 本身更损害 RV 功能。