Herein, the investigators bring together previously unconnected data to propose a unifying hypothesis, centered on insufficient NO bioavailability (INOBA), to explain the increased morbidity and mortality observed in some patients following RBC transfusion. In this model, variables associated with RBC units (storage time; 2,3-DPG concentration) and transfusion recipients (endothelial dysfunction; hematocrit [Hct]) collectively lead to changes in NO levels in vascular beds. Under certain circumstances, these variables are "aligned" such that NO concentrations are markedly reduced, leading to vasoconstriction, decreased local blood flow and insufficient O2 delivery to end organs. Under these circumstances, the likelihood of morbidity and mortality escalates. The INOBA hypothesis is attractive because of its explanatory power and because it leads to a number of readily testable predictions, which will be investigated in the following aims: