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Restoration of intracellular ATP production in banked red blood cells improves inducible ATP export and suppresses RBC-endothelial adhesion.

Publication ,  Journal Article
Kirby, BS; Hanna, G; Hendargo, HC; McMahon, TJ
Published in: Am J Physiol Heart Circ Physiol
December 15, 2014

Transfusion of banked red blood cells (RBCs) has been associated with poor cardiovascular outcomes. Storage-induced alterations in RBC glycolytic flux, attenuated ATP export, and microvascular adhesion of transfused RBCs in vivo could contribute, but the underlying mechanisms have not been tested. We tested the novel hypothesis that improving deoxygenation-induced metabolic flux and the associated intracellular ATP generation in stored RBCs (sRBCs) results in an increased extracellular ATP export and suppresses microvascular adhesion of RBCs to endothelium in vivo following transfusion. We show deficient intracellular ATP production and ATP export by human sRBCs during deoxygenation (impairments ~42% and 49%, respectively). sRBC pretreatment with a solution containing glycolytic intermediate/purine/phosphate precursors (i.e., "PIPA") restored deoxygenation-induced intracellular ATP production and promoted extracellular ATP export (improvement ~120% and 50%, respectively). In a nude mouse model of transfusion, adhesion of human RBCs to the microvasculature in vivo was examined. Only 2% of fresh RBCs (fRBCs) transfused adhered to the vascular wall, compared with 16% of sRBCs transfused. PIPA pretreatment of sRBCs significantly reduced adhesion to just 5%. In hypoxia, adhesion of sRBCs transfused was significantly augmented (up to 21%), but not following transfusion of fRBCs or PIPA-treated sRBCs (3.5% or 6%). Enhancing the capacity for deoxygenation-induced glycolytic flux within sRBCs increases their ability to generate intracellular ATP, improves the inducible export of extracellular anti-adhesive ATP, and consequently suppresses adhesion of stored, transfused RBCs to the vascular wall in vivo.

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Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

December 15, 2014

Volume

307

Issue

12

Start / End Page

H1737 / H1744

Location

United States

Related Subject Headings

  • Organ Preservation Solutions
  • Microvessels
  • Mice, Nude
  • Mice
  • Humans
  • Erythrocytes
  • Cell Hypoxia
  • Cell Adhesion
  • Cardiovascular System & Hematology
  • Blood Transfusion
 

Citation

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Kirby, B. S., Hanna, G., Hendargo, H. C., & McMahon, T. J. (2014). Restoration of intracellular ATP production in banked red blood cells improves inducible ATP export and suppresses RBC-endothelial adhesion. Am J Physiol Heart Circ Physiol, 307(12), H1737–H1744. https://doi.org/10.1152/ajpheart.00542.2014
Kirby, Brett S., Gabi Hanna, Hansford C. Hendargo, and Timothy J. McMahon. “Restoration of intracellular ATP production in banked red blood cells improves inducible ATP export and suppresses RBC-endothelial adhesion.Am J Physiol Heart Circ Physiol 307, no. 12 (December 15, 2014): H1737–44. https://doi.org/10.1152/ajpheart.00542.2014.
Kirby BS, Hanna G, Hendargo HC, McMahon TJ. Restoration of intracellular ATP production in banked red blood cells improves inducible ATP export and suppresses RBC-endothelial adhesion. Am J Physiol Heart Circ Physiol. 2014 Dec 15;307(12):H1737–44.
Kirby, Brett S., et al. “Restoration of intracellular ATP production in banked red blood cells improves inducible ATP export and suppresses RBC-endothelial adhesion.Am J Physiol Heart Circ Physiol, vol. 307, no. 12, Dec. 2014, pp. H1737–44. Pubmed, doi:10.1152/ajpheart.00542.2014.
Kirby BS, Hanna G, Hendargo HC, McMahon TJ. Restoration of intracellular ATP production in banked red blood cells improves inducible ATP export and suppresses RBC-endothelial adhesion. Am J Physiol Heart Circ Physiol. 2014 Dec 15;307(12):H1737–H1744.

Published In

Am J Physiol Heart Circ Physiol

DOI

EISSN

1522-1539

Publication Date

December 15, 2014

Volume

307

Issue

12

Start / End Page

H1737 / H1744

Location

United States

Related Subject Headings

  • Organ Preservation Solutions
  • Microvessels
  • Mice, Nude
  • Mice
  • Humans
  • Erythrocytes
  • Cell Hypoxia
  • Cell Adhesion
  • Cardiovascular System & Hematology
  • Blood Transfusion