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.

这项研究的主要目的是确定急性血管内溶血犬模型中静脉内钠的治疗值。一氧化氮（NO）是一种血管扩张剂，由血管内皮不断产生。循环中没有可用的量部分由NO与血红蛋白的结合所调节。血红蛋白通常包含在红细胞内，并以相对较慢的速率与一氧化氮反应。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。 溶血期间释放到循环中的无细胞血红蛋白的结合速度比红细胞内的血红蛋白快得多。 NO对无细胞血红蛋白的这种快速结合破坏了循环内NO的正常平衡，并导致NO可用量减少。可用的无导致血管收缩的数量减少，随后导致血流和器官损伤减少。 亚硝酸钠可以与无细胞的血红蛋白结合，并可能阻止无细胞血红蛋白结合至NO。如果亚硝酸盐可以防止无细胞的血红蛋白结合NO，则可以防止在溶血期间发生的血管收缩和器官损伤。这项研究测试了亚硝酸盐预防溶血中NO的无细胞血红蛋白结合的能力。 这项使用静脉内硝酸钠的研究是一项研究的后续研究，该研究发现使用一氧化氮气体来阻断血管收缩并最大程度地减少血管内溶解过程中的器官损伤。我们发现亚硝酸盐与生效相似，但不如一氧化氮发现那么强大。这项研究已经完成，目前正在分析结果。预计将在未来3-4个月内完成手稿。