ABSTRACT
ABSTRACT: Blood products are the current standard for resuscitation of hemorrhagic shock. However, logistical constraints of perishable blood limit availability and prehospital 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 (P ISFo2 ) in the spinotrapezius muscle. Fifty-percent isovolemic ET of estimated total blood volume with either lactated Ringer's solution (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 P ISFo2 at baseline with a transient 18 ± 4 mm Hg decrease ( P < 0.05) in mean arterial pressure (MAP). In contrast, ET with LRS decreased P ISFo2 by approximately 50% ( P < 0.05) and MAP by 74 ± 10 mm Hg ( 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. baseline) thereafter, likely from VS -101 vascular clearance. No arteriolar vasoconstriction was observed following VS -101 treatment. In this model of severe ET, VS -101 effectively maintained blood pressure, perfusion, and P ISFo2 with no vasoconstrictive effects. Further elucidation of these beneficial resuscitation effects of VS -101 is warranted to support future clinical trials.
