Low-volume Resuscitation with VS-101, a Next-Generation PEGylated HBOC, Improves Survival after Severe Hemorrhagic Shock in Rats.

Abstract

Abstract: Over 30% of trauma-related deaths are from massive hemorrhage with 90% of potentially preventable battlefield deaths occurring pre-hospital. Immediate resuscitation with whole blood is ideal but often limited to hospital and medical treatment facilities. Shelf-stable hemoglobin-based oxygen carriers (HBOCs) are designed to relieve the hypoperfusion and hypoxia of shock during the critical pre-hospital period. A new PEGylated human HBOC product, VS-101, with high oxygen affinity and hyperoncotic pressure, has been designed for hypovolemic resuscitation protocols at the point of injury. Thirty-six Sprague-Dawley rats underwent a severe, pressure-guided 45% total blood volume (TBV) hemorrhage. Shocked animals were randomly assigned to receive 20% TBV Lactated Ringers' (LRS), Plasma, Blood, or VS-101. Cardiovascular parameters, arterial blood gases, 8-hr survival, arteriolar diameters, and oxygenation of the spinotrapezius microvasculature were measured. Even compared with whole blood, VS-101 was the only group with survivors (67%) at the end of the 8-hr observation period. Mean survival times were 49, 95, 197, and 426 min for LRS, Plasma, Blood, and VS-101 (p < 0.05 vs all), respectively. VS-101 produced the highest spinotrapezius interstitial oxygenation and recovery of MAP with no evidence of hypertension or arteriolar vasoconstriction. Hypovolemic resuscitation with VS-101 was effective in stabilizing hemorrhagic shock in a simulated pre-hospital setting, which was associated with its combination of high oncotic pressure and oxygen carrying constituent. The lack of arteriolar vasoconstriction and hypertension suggests VS-101 is poised to pass critical safety and efficacy checkpoints for treatment of severe hemorrhage.