S-nitrosylation therapy to improve oxygen delivery of banked blood

James D. Reynolds, Kyla M. Bennett, Anthony J. Cina, Diana L. Diesen, Matthew B. Henderson, Faisal Matto, Andrew Plante, Rachel A. Williamson, Keivan Zandinejad, Ivan T. Demchenko, Douglas T. Hess, Claude A. Piantadosi, Jonathan S. Stamler

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

From the perspectives of disease transmission and sterility maintenance, the world's blood supplies are generally safe. However, in multiple clinical settings, red blood cell (RBC) transfusions are associated with adverse cardiovascular events and multiorgan injury. Because ∼85 million units of blood are administered worldwide each year, transfusion-related morbidity and mortality is a major public health concern. Blood undergoes multiple biochemical changes during storage, but the relevance of these changes to unfavorable outcomes is unclear. Banked blood shows reduced levels of S-nitrosohemoglobin (SNO-Hb), which in turn impairs the ability of stored RBCs to effect hypoxic vasodilation. We therefore reasoned that transfusion of SNO-Hb-deficient blood may exacerbate, rather than correct, impairments in tissue oxygenation, and that restoration of SNO-Hb levels would improve transfusion efficacy. Notably in mice, administration of banked RBCs decreased skeletal muscle pO2, but infusion of renitrosylated cells maintained tissue oxygenation. In rats, hemorrhage-induced reductions in muscle pO2 were corrected by SNO-Hb-repleted RBCs, but not by control, stored RBCs. In anemic awake sheep, stored renitrosylated, but not control RBCs, produced sustained improvements in O2 delivery; in anesthetized sheep, decrements in hemodynamic status, renal blood flow, and kidney function incurred following transfusion of banked blood were also prevented by renitrosylation. Collectively, our findings lend support to the idea that transfusions may be causally linked to ischemic events and suggest a simple approach to prevention (i.e., SNO-Hb repletion). If these data are replicated in clinical trials, renitrosylation therapy could have significant therapeutic impact on the care of millions of patients.

Original languageEnglish (US)
Pages (from-to)11529-11534
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number28
DOIs
StatePublished - Jul 9 2013

Keywords

  • Ethyl nitrite
  • Hemoglobin cysbeta93
  • Nitric oxide
  • Storage lesion

ASJC Scopus subject areas

  • General

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    Reynolds, J. D., Bennett, K. M., Cina, A. J., Diesen, D. L., Henderson, M. B., Matto, F., Plante, A., Williamson, R. A., Zandinejad, K., Demchenko, I. T., Hess, D. T., Piantadosi, C. A., & Stamler, J. S. (2013). S-nitrosylation therapy to improve oxygen delivery of banked blood. Proceedings of the National Academy of Sciences of the United States of America, 110(28), 11529-11534. https://doi.org/10.1073/pnas.1306489110