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

亚硝酸钠对犬模型急性溶血的影响

• 批准号: 7593076
• 负责人: Charles Natanson
• 金额: $ 11.99万
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7593076
• 关键词: Acute; Binding; Blood Circulation; Blood flow; Canis familiaris; Cells; Equilibrium; Erythrocytes; Gases; Goals; Hemoglobin; Hemolysis; Injury; Intravenous; Manuscripts; Modeling; Nitric Oxide; Nitrites; Organ; Rate; Sodium Nitrite; Testing; Therapeutic; Vascular Endothelium; Vasodilator Agents; follow-up; prevent; vasoconstriction

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.

本研究的主要目的是确定静脉注射亚硝酸钠在急性血管内溶血犬模型中的治疗价值。一氧化氮（NO）是一种血管扩张剂，其由血管内皮持续产生。循环中可用的NO的量部分地由NO与血红蛋白的结合来调节。血红蛋白通常包含在红细胞中，并以相对缓慢的速度与一氧化氮反应。然而，循环中红细胞的破坏（血管内溶血）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以比红细胞内的血红蛋白快得多的速率与NO结合。无细胞血红蛋白对NO的快速结合破坏了循环中NO的正常平衡，并导致可用NO量的减少。这种可用NO量的减少导致血管收缩，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游离血红蛋白结合，并可能阻止游离血红蛋白与NO结合。如果亚硝酸盐可以阻止游离血红蛋白与NO结合，则可以防止溶血过程中发生的血管收缩和器官损伤。本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研究，该研究发现了使用一氧化氮气体阻断血管收缩的有效性，并最大限度地减少了血管内溶血期间引起的器官损伤。我们发现亚硝酸盐的作用类似于一氧化氮，但不如我们的发现那么强大。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。