Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Curr Opin Hematol. 2009 Nov;16(6):515-23. doi: 10.1097/MOH.0b013e32833157f4.
Whereas blood storage is associated with an increased risk of cardiovascular events and multiorgan failure, the fundamental mechanisms underlying the 'storage lesion' in blood remain uncertain. A major abnormality in aged blood is the reduced red cell life-span after infusion, which is associated with microparticle and free hemoglobin release, and age-related loss of enzymatic functionality. However, the degree of intravascular hemolysis and microparticle formation in humans post-transfusion due to both storage and physiological shear has not been well studied.
Our laboratories have discovered that even low levels of intravascular hemolysis severely disrupt nitric oxide bioavailability at the endothelium, via accelerated nitric oxide dioxygenation reactions with free plasma hemoglobin. This process contributes to endothelial dysfunction, adhesion molecule expression, platelet and hemostatic activation, and reactive oxygen species generation. Recent studies also suggest that red cells possess nitric oxide-generating functionality via nitrite reduction and red cell endothelial nitric oxide synthase activity, potentially providing novel pathways to therapeutically alleviate the 'storage lesion'.
The understanding of the pathological effects of red cell hemolysis on endothelial function suggests that nitric oxide dysregulation may underlie the red cell storage lesion, driven by increased nitric oxide catabolism and loss of nitric oxide-generating functionality.
尽管血液储存与心血管事件和多器官衰竭的风险增加有关，但血液“储存损伤”的基本机制仍不确定。老年血液的一个主要异常是输注后红细胞寿命缩短，这与微粒体和游离血红蛋白的释放以及与年龄相关的酶功能丧失有关。然而，由于储存和生理剪切，输注后人体中由于储存和生理剪切导致的血管内溶血和微粒体形成的程度尚未得到很好的研究。
我们的实验室发现，即使是低水平的血管内溶血也会通过与游离血浆血红蛋白的加速一氧化氮双加氧反应，严重破坏内皮细胞中一氧化氮的生物利用度。这个过程导致内皮功能障碍、黏附分子表达、血小板和止血激活以及活性氧生成。最近的研究还表明，红细胞通过亚硝酸盐还原和红细胞内皮型一氧化氮合酶活性产生一氧化氮生成功能，可能为治疗性缓解“储存损伤”提供新的途径。
对红细胞溶血对内皮功能的病理影响的认识表明，一氧化氮失调控可能是红细胞储存损伤的基础，其原因是一氧化氮分解代谢增加和一氧化氮生成功能丧失。
