Abstract 14081: Preservation of Myocardial Cotractility During Acute Hypoxia With OMX, a Novel Oxygen Delivery Biotherapeutic
Introduction: The heart has the highest oxygen consumption per tissue mass of any organ. During acute hypoxia, myocardial O2 consumption is further elevated as the heart attempts to preserve systemic O2 delivery by increasing heart rate. This exposes the heart to potential ischemic stress, myocardial dysfunction and cardiac failure. Omniox, Inc. has developed a stable, well characterized and easily administered agent, OMX, that belongs to the oxygen-carrying protein family, H-NOX, and is derived from a thermostable protein originating from the thermophilic bacterium, Thermoanaerobacter tengcongensis. OMX restores physiologic oxygen levels in oxygen-deprived tissues, but does not hyper-oxygenate tissues that have physiologic levels of oxygen. Additionally, unlike previous hemoglobin-based oxygen carriers whose development was blocked by the FDA from further development due to their vasoconstrictive effects, OMX does not scavenge nitric oxide.
Hypothesis: OMX will preserve myocardial contractility in the setting of global hypoxia.
Methods: Juvenile lambs (age 4-6 weeks) were sedated, mechanically ventilated, and instrumented to measure vascular pressure and flow. Admittance catheters were inserted into the left and right ventricle to perform pressure-volume (PV) loop analysis. Systemic hypoxia was induced by ventilating the lambs with 10% oxygen for one hour. Fifteen minutes into hypoxia, the lambs received OMX (200 mg/kg IV) or vehicle (n=5 per group).
Results: Acute hypoxia induced a significant increase in HR, PBF, PVR, and a decrease in systemic PaO2 (p value <0.05). There were no significant differences in hemodynamics or blood gases between the groups. After one hour of systemic hypoxia, PV loop analysis demonstrated a reproducible decrease in right and left ventricle (RV and LV) contractile function in vehicle-treated lambs, as evidenced by a decrease in the slope of the end systolic PV relationship, Ees (RV 64±24% baseline, LV 53±25% baseline, p value <0.05). OMX infusion, however, maintained RV and LV Ees at baseline normoxia levels.
Conclusions: OMX represents a promising novel oxygen delivery biotherapeutic for the preservation of myocardial contractility in the setting of acute hypoxia.
Author Disclosures: J. Boehme: None. N. LeMoan: Ownership Interest; Significant; Omniox, Inc.. R.J. Kameny: None. A. Loucks: Ownership Interest; Significant; Omniox, Inc.. M. Johengen: None. A. Lesneski: None. W. Gong: None. Y. He: None. T. Davis: Employment; Significant; Omniox, Inc.. S. Datar: None. J. Fineman: Consultant/Advisory Board; Significant; Omniox, Inc. A. Krtolica: Ownership Interest; Significant; Omniox, Inc. E. Maltepe: Consultant/Advisory Board; Significant; Omniox, Inc..
- © 2016 by American Heart Association, Inc.