Nitric Oxide Scavenging by Red Blood Cell Microparticles and Cell-Free Hemoglobin as a Mechanism for the Red Cell Storage Lesion

被引:493
作者
Donadee, Chenell [1 ,2 ]
Raat, Nicolaas J. H. [1 ,2 ,6 ]
Kanias, Tamir [1 ]
Tejero, Jesus [1 ]
Lee, Janet S. [1 ,2 ]
Kelley, Eric E. [1 ,4 ]
Zhao, Xuejun [1 ,2 ]
Liu, Chen [7 ]
Reynolds, Hannah [7 ]
Azarov, Ivan [7 ]
Frizzell, Sheila [1 ]
Meyer, E. Michael [8 ]
Donnenberg, Albert D. [3 ,8 ]
Qu, Lirong [5 ,9 ]
Triulzi, Darrel [5 ,9 ]
Kim-Shapiro, Daniel B. [7 ]
Gladwin, Mark T. [1 ,2 ]
机构
[1] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA
[2] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA
[3] Univ Pittsburgh, Sch Med, Div Hematol Oncol, Pittsburgh, PA USA
[4] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA
[5] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA
[6] Erasmus MC, Dept Expt Anesthesiol, Rotterdam, Netherlands
[7] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA
[8] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA
[9] Inst Transfus Med, Pittsburgh, PA USA
基金
美国国家卫生研究院;
关键词
hemoglobin; microparticles; cell-derived; nitric oxide; blood transfusion; blood; storage lesion; reactive oxygen species; PULMONARY-HYPERTENSION; CLINICAL CONSEQUENCES; HUMAN ERYTHROCYTES; PLASMA HEMOGLOBIN; TRANSFUSED BLOOD; S-NITROSOTHIOLS; CRITICALLY-ILL; RISK-FACTOR; HEMOLYSIS; VESICLES;
D O I
10.1161/CIRCULATIONAHA.110.008698
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Intravascular red cell hemolysis impairs nitric oxide (NO)-redox homeostasis, producing endothelial dysfunction, platelet activation, and vasculopathy. Red blood cell storage under standard conditions results in reduced integrity of the erythrocyte membrane, with formation of exocytic microvesicles or microparticles and hemolysis, which we hypothesized could impair vascular function and contribute to the putative storage lesion of banked blood. Methods and Results-We now find that storage of human red blood cells under standard blood banking conditions results in the accumulation of cell-free and microparticle-encapsulated hemoglobin, which, despite 39 days of storage, remains in the reduced ferrous oxyhemoglobin redox state and stoichiometrically reacts with and scavenges the vasodilator NO. Using stopped-flow spectroscopy and laser-triggered NO release from a caged NO compound, we found that both free hemoglobin and microparticles react with NO about 1000 times faster than with intact erythrocytes. In complementary in vivo studies, we show that hemoglobin, even at concentrations below 10 mu mol/L (in heme), produces potent vasoconstriction when infused into the rat circulation, whereas controlled infusions of methemoglobin and cyanomethemoglobin, which do not consume NO, have substantially reduced vasoconstrictor effects. Infusion of the plasma from stored human red blood cell units into the rat circulation produces significant vasoconstriction related to the magnitude of storage-related hemolysis. Conclusions-The results of these studies suggest new mechanisms for endothelial injury and impaired vascular function associated with the most fundamental of storage lesions, hemolysis. (Circulation. 2011; 124: 465-476.)
引用
收藏
页码:465 / U294
页数:24
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