Effects of Sanguinate on Systemic and Microcirculatory Variables in a Model of Prolonged Hemorrhagic Shock

Abstract

Hemorrhage and its complications are the leading cause of preventable death from trauma in young adults, especially in remote locations. To address this, deliverable, shelf-stable resuscitants that provide therapeutic benefits throughout the time course of hemorrhagic shock and the progressive ischemic injury it produces are needed. SANGUINATE is a novel bovine PEGylated carboxyhemoglobin-based oxygen carrier, which has desirable oxygen-carrying and oncotic properties as well as a CO moiety to maintain microvascular perfusion. To compare the crystalloid (Lactated Ringer's Solution; LRS), and the colloid (Hextend) standards of care with SANGUINATE in a post "golden hour" resuscitation model. Rats underwent a controlled, stepwise blood withdrawal (45% by volume), were maintained in untreated hemorrhagic shock state for >60 min, resuscitated with a 20% bolus of one of the three test solutions, and observed till demise. Parameters of tissue oxygenation (PISFO2), arteriolar diameters, and mean arterial pressure (MAP) were collected. SANGUINATE-treated animals survived significantly longer than those treated with Hextend and LRS. SANGUINATE also significantly increased tissue PISFO2 2 h after resuscitation, whereas LRS and Hextend did not. SANGUINATE also produced a significantly higher MAP, which was hypotensive compared to baseline, that endured until demise. Resuscitation with SANGUINATE after prolonged hemorrhagic shock improves survival, MAP, and PISFO2 compared with standard of care plasma expanders. Since the pathologies of hemorrhagic shock and the associated systemic ischemia are progressive, preclinical studies of this nature are essential to determine efficacy of new resuscitants across the range of possible times to treatment.