Role of Altered Blood Properties in the Propagation of Ischemic Blood Flow: Contribution of Aging and Oxidative Stress

The red blood cell (RBC) undergoes enhanced oxidative processes at reduced oxygen pressures. They originate from the dramatic increase in the rates of autoxidation for partially oxygenated hemoglobin and the associated production of superoxide. The basis for this form of oxidative stress and its ramifications have been reviewed. The release of superoxide by hemoglobin has been implicated in heme degradation, damage to the RBC membrane, leakage of reactive oxygen molecules into the plasma, and the potential beneficial release of NO from S-nitrosylated hemoglobin. It has further been shown that these oxidative reactions can escape the RBC antioxidant defenses when taking place on the hemoglobin bound to the RBC membrane. During aging increased hypoxia results in enhanced oxidative stress, which is consistent with large RBCs, decreased deformability and increased viscosity. Furthermore, the deficiency in vitamin B12 may limit the level of S-nitrosylation decreasing the release of NO associated with hemoglobin autoxidation. The synergistic relation coupling hypoxia-oxidative stress-altered RBC properties further increases hypoxia and provides a mechanism for exacerbated decrements in flow during aging or pathological conditions, which can result in ischemic stress. The relevance of these hemorheological and oxidative perturbations has been validated by blood flow velocity studies of the cerebral and carotid arteries.