Exchange Transfusion With vs-101: A New Pegylated-Hb Designed to Restore Perfusion and Increase O2 Carrying Capacity

Abstract

Blood products are the current standard for resuscitation of hemorrhagic shock. However, logistical constraints of perishable blood limit availability and pre-hospital use meaning alternatives that provide blood-like responses remain an area of active investigation and development. VS-101 is a new PEGylated human hemoglobin-based oxygen carrier that avoids the logistical hurdles of traditional blood transfusion. This study sought to determine the safety and ability of VS-101 to maintain circulatory function and capillary oxygen delivery in a severe (50%) exchange transfusion (ET) model. Anesthetized, male Sprague Dawley rats were prepared for cardiovascular monitoring and phosphorescence quenching microscopy of interstitial fluid oxygen tension (PISFO2) in the spinotrapezius muscle. 50% isovolemic ET of estimated total blood volume with either Lactated Ringer’s (LRS; N = 8) or VS-101 (N = 8) at 1 mL/kg/min was performed, and animals were observed for 240 min. VS-101 maintained PISFO2 at baseline (BL) with a transient 18 ± 4 mmHg decrease (p < 0.05) in mean arterial pressure (MAP). In contrast, ET with LRS decreased PISFO2 by ~50% (p < 0.05) and MAP by 74 ± 10 mmHg (p < 0.05). All VS-101 animals survived 240 min, the experimental endpoint, while 100% of LRS animals expired by 142 min. VS-101 animals maintained normal tissue oxygenation through 210 min, decreasing by 25% (p < 0.05 vs. BL) thereafter, likely from VS-101 vascular clearance. No arteriolar vasoconstriction was observed following VS-101 treatment. In this model of severe exchange transfusion, VS-101 effectively maintained blood pressure, perfusion, and PISFO2 with no vasoconstrictive effects. Further elucidation of these beneficial resuscitation effects of VS-101 is warranted to support future clinical trials.