The Effect of Sodium Nitrite on Acute Hemolysis in a Canine Model

本研究的主要目的是确定静脉注射亚硝酸钠在犬急性血管内溶血模型中的治疗价值。一氧化氮(NO)是一种血管扩张剂，由血管内皮细胞持续产生。循环中可利用的NO的数量部分地受NO与血红蛋白结合的调节。血红蛋白通常包含在红细胞中，与一氧化氮的反应速度相对较慢。然而，循环内红细胞的破坏(血管内溶血)会导致血红蛋白(无细胞血红蛋白)从红细胞释放到循环中。在溶血过程中释放到循环中的无细胞血红蛋白与NO的结合速度比红细胞内的血红蛋白快得多。这种NO与无细胞血红蛋白的快速结合破坏了循环内NO的正常平衡，并导致可用的NO数量减少。这种可利用的NO数量的减少会导致血管收缩，随后导致血流量减少和器官损伤。静脉注射亚硝酸钠可以与无细胞血红蛋白结合，并可能阻止无细胞血红蛋白与NO结合。如果亚硝酸盐能阻止无细胞血红蛋白与NO结合，它可能会防止溶血过程中发生的血管收缩和器官损伤。这项研究测试了亚硝酸盐在溶血过程中阻止NO与无细胞血红蛋白结合的能力。 这项使用静脉注射亚硝酸钠的研究是一项研究的后续，该研究发现使用一氧化氮气体可以有效地阻断血管收缩，并将血管内溶血过程中造成的器官损害降至最低。我们发现亚硝酸盐在效果上类似于我们发现的一氧化氮，但没有我们发现的那么强大。这项研究已经完成，目前正在分析结果。手稿预计将在未来3-4个月内完成。

The primary goal of this study was to determine the therapeutic value of intravenous sodium nitrite in a canine model of acute intravascular hemolysis. Nitric oxide (NO) is a vasodilator which is constantly produced by the vascular endothelium. The amount of NO available in the circulation is, in part, regulated by the binding of NO to hemoglobin. Hemoglobin is normally contained within the red blood cell and reacts with nitric oxide at a relatively slow rate. However, the destruction of red blood cells within the circulation (intravascular hemolysis) causes the release of hemoglobin (cell-free hemoglobin) from the red blood cell into the circulation. The cell-free hemoglobin released into the circulation during hemolysis binds to NO at a much faster rate than hemoglobin within the red blood cell. This rapid binding of NO by cell-free hemoglobin disrupts the normal balance of NO within the circulation and leads to a decrease in the amount of NO available. This decrease in the amount of available NO leads to vasoconstriction and subsequently to decreased blood flow and organ injury. Intravenous sodium nitrite can bind to cell-free hemoglobin and may prevent the cell-free hemoglobin from binding to NO. If the nitrite can prevent the cell-free hemoglobin from binding NO, it may prevent the vasoconstriction and organ injury that occurs during hemolysis. This study tested the ability of nitrite to prevent cell-free hemoglobin binding of NO during hemolysis. This study using intravenous sodium nitrite is a follow-up to a study which found efficacy in using nitric oxide gas to block vasoconstriction and minimize organ damage caused during intravascular hemolysis. We found that nitrite is similar to in effect but not as powerful as our finding with nitric oxide. This study has been completed and the results are presently being analyzed. A manuscript is expected to be completed in the next 3-4 months.