A Novel Cross-Linked Hemoglobin-Based Oxygen Carrier, YQ23, Extended the Golden Hour for Uncontrolled Hemorrhagic Shock in Rats and Miniature Pigs

Abstract

Background: Hypotensive resuscitation is widely applied for trauma and war injury to reduce bleeding during damage-control resuscitation, but the treatment time window is limited in order to avoid hypoxia-associated organ injury. Whether a novel hemoglobin-based oxygen carrier (HBOC), YQ23 in this study, could protect organ function, and extend the Golden Hour for treatment is unclear.Method: Uncontrolled hemorrhagic shock rats and miniature pigs were infused with 0.5, 2, and 5% YQ23 before bleeding was controlled, while Lactate Ringer’s solution (LR) and fresh whole blood plus LR (WB + LR) were set as controls. During hypotensive resuscitation the mean blood pressure was maintained at 50–60 mmHg for 60 min. Hemodynamics, oxygen delivery and utilization, blood loss, fluid demand, organ function, animal survival as well as side effects were observed. Besides, in order to observe whether YQ23 could extend the Golden Hour, the hypotensive resuscitation duration was extended to 180 min and animal survival was observed.Results: Compared with LR, infusion of YQ23 in the 60 min pre-hospital hypotensive resuscitation significantly reduced blood loss and the fluid demand in both rats and pigs. Besides, YQ23 could effectively stabilize hemodynamics, and increase tissue oxygen consumption, increase the cardiac output, reduce liver and kidney injury, which helped to reduce the early death and improve animal survival. In addition, the hypotensive resuscitation duration could be extended to 180 min using YQ23. Side effects such as vasoconstriction and renal injury were not observed. The beneficial effects of 5% YQ23 are equivalent to similar volume of WB + LR.Conclusion: HBOC, such as YQ23, played vital roles in damage-control resuscitation for emergency care and benefited the uncontrolled hemorrhagic shock in the pre-hospital treatment by increasing oxygen delivery, reducing organ injury. Besides, HBOC could benefit the injured and trauma patients by extending the Golden Hour.

The Characteristics of Organ Function Damage of Hemorrhagic Shock in Hot Environment and the Effect of Hypothermic Fluid Resuscitation

“…The vital organ functions were observed with hemorrhagic shock in 348C hot environment. The results showed that hemorrhagic shock led to vital organ function damage in room temperature environment similar with previous studies (12). It was shown that CO, CI, and SI were decreased and AST, ALT (liver damage parameter), BUN, Crea (kidney damage parameter) were increased significantly.…”

How Nitric Oxide Hindered the Search for Hemoglobin-Based Oxygen Carriers as Human Blood Substitutes

“…The resulting cross-linked tetramers were produced in a high yield and were isolated and characterized [136], but we are not aware of successful clinical trials employing these derivatives. Remarkably, YQ23, a bovine-derived cross-linked Hb, more resistant to oxidation, with a low Hb + content (<4.8%) and P50 = 40 mmHg, was tested in rats and pigs, with favorable outcomes in terms of hypotensive resuscitation, stabilized hemodynamics, an increased tissue O 2 consumption, increased cardiac output, and reduced liver and kidney injury [137], but we are not aware of any clinical trials performed with this HBOC.…”

Silk Fibroin Particles as Carriers in the Development of Hemoglobin‐Based Oxygen Carriers

“…[21] To address these challenges, strategies to increase the molecular diameter of the HBOC and limit free hemoglobin in circulation have become requirements in the design of modern HBOCs. These strategies include chemical cross-linking of hemoglobin, [22,23] polymerization of hemoglobins, [24][25][26] and encapsulation of hemoglobin in liposome and nano-and microparticle systems. [27,28] Liposome encapsulated hemoglobin's have demonstrated many of the desired design criteria for an alternative oxygen carrier, including an absence of blood group antigens and blood-borne pathogens, and a prolonged storage capacity.…”