S -nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood

Abstract

RBCs distribute oxygen to tissues, but, paradoxically, blood transfusion does not always improve oxygen delivery and is associated with ischemic events. We hypothesized that storage of blood would result in loss of NO bioactivity, impairing RBC vasodilation and thus compromising blood flow, and that repleting NO bioactivity would restore RBC function. We report that S-nitrosohemoglobin (SNO-Hb) concentrations declined rapidly after storage of fresh venous blood and that hypoxic vasodilation by banked RBCs correlated strongly with the amounts of SNO-Hb (r 2 ‫؍‬ 0.90; P < 0.0005). Renitrosylation of banked blood during storage increased the SNO-Hb content and restored its vasodilatory activity. In addition, canine coronary blood flow was greater during infusion of renitrosylated RBCs than during infusion of S-nitrosothiol-depleted RBCs, and this difference in coronary flow was accentuated by hypoxemia (P < 0.001). Our findings indicate that NO bioactivity is depleted in banked blood, impairing the vasodilatory response to hypoxia, and they suggest that SNO-Hb repletion may improve transfusion efficacy.blood preservation ͉ blood transfusion ͉ erythrocytes ͉ hypoxic vasodilation ͉ S-nitrosylation

Anemia and splenomegaly in cGKI-deficient mice

“…Similar to what has been shown in nucleated cells (43,44), NO may further be effective in erythrocytes through nitrosylation of enzymes necessary for induction of cell membrane scrambling (42). Because NO is released from deoxygenated erythrocytes (45)(46)(47), the antieryptotic effect of NO would be particularly important in hypoxic tissue. Impaired NO formation in erythrocytes has been implicated in the vasoconstriction and ischemia after transfusion (46,47), pulmonary hypertension (39), and deranged microcirculation in sickle cell anemia (48).…”

Stiffness increase of red blood cells during storage

“…Interestingly, this timing matches well with the degradation pattern of SNO. It is known that the SNO level decreases by 70% after only one day of RBC storage and that by the end of the first week of storage, up to 90% of the SNO is depleted 40 , as shown in Figure 6b. Thus, we reason that the significant depletion of SNO in the first week of RBC storage caused the significant RBC stiffness increase by the first week as our data revealed (1 week: 37.2 ± 8.6 μN m −1 ; fresh: 26.5 ± 8.3 μN m −1 ).…”

“…Another protein, protein 4.1, also plays a key role in regulating membrane stiffness by interacting with spectrin and glycophorin, and their interactions are modulated by phosphorylation, a process that involves the addition of a phosphate to an organic compound by consuming ATP 39 . The structure and the interactions between these proteins change during RBC storage due to the degradation of several biochemical parameters, such as SNO and ATP [40][41][42] . The degradation of these biochemical parameters over the RBC storage process has been widely reported, and the depletion of SNO and ATP has been speculated to play important roles in regulating RBCs' mechanical properties 39,[43][44][45] .…”

“…The degradation of these biochemical parameters over the RBC storage process has been widely reported, and the depletion of SNO and ATP has been speculated to play important roles in regulating RBCs' mechanical properties 39,[43][44][45] . During RBC storage, the SNO level becomes lower, leading to a lower activity of S-nitrosylation 40 . The detachment between spectrin and ankryin, which is induced by S-nitrosylation, becomes less frequent, and the detached end of spectrin thermally diffuses back to ankyrin and reattaches 38,46 .…”

“…There also are some technical issue that deserves more investigation. To better understand the effect of biochemical degradation on the changes in RBC stiffness, performing biochemical measurements on single RBCs and stiffness measurements on the same RBCs, different from existing studies on RBC populations [40][41][42] , would permit a more precise correlation.…”