S-nitrosohemoglobin deficiency: A mechanism for loss of physiological activity in banked blood
- James D. Reynolds*,
- Gregory S. Ahearn†,
- Michael Angelo†,
- Jian Zhang†,
- Fred Cobb†,‡, and
- Jonathan S. Stamler†,§,¶
- Departments of *Anesthesiology,
- †Medicine, and
- §Biochemistry, Duke University Medical Center, Durham, NC 27710
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Communicated by Irwin Fridovich, Duke University Medical Center, Durham, NC, August 24, 2007 (received for review June 13, 2007)
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.
Footnotes
- ¶To whom correspondence should be addressed at: Duke University Medical Center, Medical Science Research Building, Room 321, Box 2612, Durham, NC 27710. E-mail: staml001{at}mc.duke.edu
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Author contributions: J.D.R. and G.S.A. contributed equally to this work; J.D.R., G.S.A., and J.S.S. designed research; J.D.R., G.S.A., M.A., J.Z., and F.C. performed research; J.D.R. and J.S.S. contributed new reagents/analytic tools; J.D.R., G.S.A., M.A., and J.S.S. analyzed data; and J.D.R., G.S.A., M.A., and J.S.S. wrote the paper.
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↵ ‡Deceased January 30, 2006.
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Conflict of interest statement: J.S.S. and J.D.R. have consulting and/or equity relationships with Nitrox/N30, a company that is developing strategies for treating disorders of oxygen delivery
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This article contains supporting information online at www.pnas.org/cgi/content/full/0707958104/DC1.
- Abbreviations:
- Hb[FeNO],
- iron nitrosyl Hb;
- SNO,
- S-nitrosothiol;
- SNO-Hb,
- S-nitrosohemoglobin.
- © 2007 by The National Academy of Sciences of the USA
