P71: Nitrite and nitric oxide supplementation during erythrocyte storage

Abstract

Background Several studies have shown that aging red blood cells (RBCs) during storage reduces their ability to improve microvascular perfusion and oxygenation after transfusion. In this study we investigated the role of nitric oxide (NO) and nitrite supplementation during storage of RBCs. In order to study the roles of NO and nitrite in the various biochemical changes during RBC storage, NO-releasing agents, NO releasing nanoparticles (NO-nps) and nitrite were used. Methods Rat cells were stored for 14 days at 4 °C in CDPA-1, during storage NO-releasing agents, NO-nps and nitrite were supplemented at various doses. Biochemical and biomechanical changes were quantified and compared to fresh cells. Additionally, rats were instrumented and exchange transfused with stored cells with and without NO supplementation. Results During the storage duration 2,3-DPG concentration and pH decreased, and increased lactate. NO supplementation with NO-nps slowed down the biochemical changes including the depletion on important antioxidant factors, such as GSH, NADP and NADPH. NO supplementation with NO-nps decreased proteolytic enzymes, including connective tissue-activating peptide III, which participates in tissue remodeling and inflammatory process. Lastly, NO supplementation preserved static and dynamic red cell mechanics, which affect cell-to-cell and cell-to-wall interaction. Transfusion of stored cells without NO supplementation affected small arterioles hemodynamics, including diameter, velocity, blood flow, and oxygen delivery. While, infusion of cells stored under NO supplementation presented superior microvascular hemodynamics and oxygenation. Conclusions Although both NO and its donors and/or their decomposed products may have biological activities, most of the cellular responses to these donors have been postulated to reflect NO-dependent events. NO supplementation during storage preserved cell deformability, preserved antioxidant capacity and preserved microvascular endothelial cell mechanotransduction, and red cell hydrodynamics. Most of the storage changes were prevented or slowed down by NO, NO induced protection seems to be related to decrease oxidative stress in the storage conditions. Therefore, NO supplementation prevents ROS irreversible lesions in the early period of storage, rather then intervening a posteriori through the addition of rejuvenating solutions. Disclosure There is not financial interest. Supported by R01HL052684 P01HL11090.