Exchange Transfusion with VS-101: A New PEGylated-Hb Designed to Restore Perfusion and Increase O2 Carrying Capacity

Document Type

Article

Publication Date

12-13-2023

Institution/Department

Trauma & Acute Care Surgery

Journal Title

Shock (Augusta, Ga.)

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.

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