Omx: A Novel Oxygen Delivery Biotherapeutic Improves Outcomes in an Ovine Model of Controlled Hemorrhagic Shock

Abstract

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 autere environments. OMX is a novel non-hemoglobin (Hb)-based oxygen carrier derived from the H-NOX (Heme-Nitric Oxide/Oxygen binding) protein family. Due to their engineered oxygen (O2) affinities, OMX proteins only deliver O2 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 minutes. Vehicle (n = 16) or 400 mg/kg OMX (n = 13) treatment was administered over 15 minutes. Hemodynamics, arterial blood gases, and laboratory values were monitored throughout the 6 hour 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 hr., 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.