Abstract：
UNASSIGNED: Hemorrhagic shock is a major source of morbidity and mortality worldwide. While whole blood or blood product transfusion is a first-line treatment, maintaining robust supplies presents significant logistical challenges, particularly in austere environments. OMX is a novel nonhemoglobin (Hb)-based oxygen carrier derived from the H-NOX (heme-nitric oxide/oxygen binding) protein family. Because of their engineered oxygen (O 2 ) affinities, OMX proteins only deliver O 2 to severely hypoxic tissues. Additionally, unlike Hb-based oxygen carriers, OMX proteins do not scavenge nitric oxide in the vasculature. To determine the safety and efficacy of OMX in supporting tissue oxygen delivery and cardiovascular function in a large animal model of controlled hemorrhage, 2-3-week-old lambs were anesthetized, intubated, and mechanically ventilated. Hypovolemic shock was induced by acute hemorrhage to obtain a 50% reduction over 30 min. Vehicle (n = 16) or 400 mg/kg OMX (n = 13) treatment was administered over 15 min. Hemodynamics, arterial blood gases, and laboratory values were monitored throughout the 6-h study. Comparisons between groups were made using t tests, Wilcoxon rank sum test, and Fisher\'s exact test. Survival was assessed using Kaplan-Meier curves and the log-rank test. We found that OMX was well-tolerated and significantly improved lactate and base deficit trends, and hemodynamic indices ( P < 0.05). Median survival time was greater in the OMX-treated group (4.7 vs. 6.0 h, P < 0.003), and overall survival was significantly increased in the OMX-treated group (25% vs. 85%, P = 0.004). We conclude that OMX is well-tolerated and improves metabolic, hemodynamic, and survival outcomes in an ovine model of controlled hemorrhagic shock.
摘要：
失血性休克是全世界发病率和死亡率的主要来源。虽然全血或血液制品输血是一线治疗，维持稳健的供应带来了重大的后勤挑战，特别是在Autere环境中。OMX是衍生自H-NOX(血红素-一氧化氮/氧结合)蛋白家族的新型非血红蛋白(Hb)基氧载体。由于其工程氧（O2）亲和力，OMX蛋白仅将O2递送至严重缺氧组织。此外,与基于Hb的氧载体不同，OMX蛋白不能清除脉管系统中的一氧化氮。为了确定OMX在控制出血的大型动物模型中支持组织氧气输送和心血管功能的安全性和有效性，2-3周大的羔羊被麻醉，插管,机械通风。急性出血引起低血容量性休克，在30分钟内减少50％。在15分钟内施用载体(n=16)或400mg/kgOMX(n=13)治疗。血流动力学,动脉血气，在整个6小时的研究中监测实验室值。组间比较采用T检验，Wilcoxon秩和检验,和费希尔的精确检验。使用Kaplan-Meier曲线和Log-Rank检验评估存活率。我们发现OMX具有良好的耐受性，并显着改善了乳酸和碱缺乏趋势，和血液动力学指标（p<0.05）。OMX治疗组的中位生存时间更长（4.7vs.6.0小时。,p<0.003),OMX治疗组的总生存率显着提高（25％vs.85%,p=0.004)。我们得出的结论是，OMX耐受性良好，可以改善代谢，控制性失血性休克绵羊模型的血流动力学和生存结果.
