Peter Goedhart died during the writing process.
Red blood cell storage increases hypoxia-induced nitric oxide bioavailability and methemoglobin formation in vitro and in vivo
Article first published online: 18 JUN 2014
© 2014 AABB
Volume 54, Issue 12, pages 3178–3185, December 2014
How to Cite
Almac, E., Bezemer, R., Hilarius-Stokman, P. M., Goedhart, P., de Korte, D., Verhoeven, A. J. and Ince, C. (2014), Red blood cell storage increases hypoxia-induced nitric oxide bioavailability and methemoglobin formation in vitro and in vivo. Transfusion, 54: 3178–3185. doi: 10.1111/trf.12738
This study was in part supported by the Landsteiner Foundation for Blood Transfusion Research (grant no. 0329).
- Issue published online: 11 DEC 2014
- Article first published online: 18 JUN 2014
- Manuscript Accepted: 20 APR 2014
- Manuscript Revised: 19 APR 2014
- Manuscript Received: 19 OCT 2013
- Landsteiner Foundation for Blood Transfusion Research. Grant Number: 0329
In this study we investigated whether storage of red blood cells (RBCs) leads to alterations in nitrite reductase activity, hence in altered hypoxia-induced nitric oxide (NO) bioavailability and methemoglobin formation.
Study Design and Methods
Hypoxia-induced NO bioavailability and methemoglobin formation were measured in vitro after nitrite administration to fresh (<1 week of storage) and aged (5-6 weeks of storage) human RBC units and in blood samples of hemodiluted rats subjected to hypoxic ventilation after transfusion with fresh or aged human RBCs.
In vitro, NO and methemoglobin levels 10 minutes after nitrite administration were lower in the fresh RBC samples compared to the aged RBC samples (p = 0.026 and p = 0.022, respectively). In vivo, NO bioavailability was also significantly lower in the rats receiving fresh RBCs compared to the group receiving aged RBCs (p = 0.003). In line with NO bioavailability, methemoglobin levels were higher, albeit not significantly, in the group receiving aged RBCs compared to in the group receiving fresh RBCs (p = 0.154). The difference in methemoglobin formation after nitrite administration between fresh and aged RBCs was only present under deoxygenated conditions and not under oxygenated conditions. There were no differences in methemoglobin reductase activity between fresh and aged RBCs.
Storage of RBCs leads to an increased rate of hypoxia-induced nitrite reduction to NO and this is associated with increased methemoglobin formation. The increased methemoglobin formation and consequent decrease in oxygen delivery capacity might contribute to the storage-related impairment of aged RBCs to oxygenate the microcirculation.