Abstract
BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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% O(2)). RESULTS: 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. CONCLUSIONS: 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.