Kuang Lei, Zhu Yu, Wu Yue, Tian Kunlun, Peng Xiaoyong, Xue Mingying, Xiang Xinming, Lau Billy, Tzang Fei Chuen, Liu Liangming, Li Tao
State Key Laboratory of Trauma, Burns and Combined Injury, Department of Shock and Transfusion, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
New Beta Innovation Limited, Chevalier Commercial Center, Kowloon Bay, Hong Kong, China.
Front Pharmacol. 2021 May 12;12:652716. doi: 10.3389/fphar.2021.652716. eCollection 2021.
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. 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. 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. 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.
低血压复苏广泛应用于创伤和战伤，以在损伤控制复苏期间减少出血，但为避免缺氧相关器官损伤，治疗时间窗有限。本研究中的新型基于血红蛋白的氧载体（HBOC）YQ23是否能保护器官功能并延长黄金治疗时间尚不清楚。在控制出血前，对失血性休克大鼠和小型猪输注0.5%、2%和5%的YQ23，同时设置乳酸林格氏液（LR）以及新鲜全血加LR（WB + LR）作为对照。在低血压复苏期间，平均血压维持在50 - 60 mmHg达60分钟。观察血流动力学、氧输送与利用、失血量、液体需求量、器官功能、动物存活率以及副作用。此外，为观察YQ23是否能延长黄金时间，将低血压复苏持续时间延长至180分钟并观察动物存活率。与LR相比，在院前60分钟低血压复苏中输注YQ23可显著减少大鼠和猪的失血量及液体需求量。此外，YQ23可有效稳定血流动力学，增加组织氧消耗，增加心输出量，减轻肝肾损伤，有助于减少早期死亡并提高动物存活率。另外，使用YQ23可将低血压复苏持续时间延长至180分钟。未观察到血管收缩和肾损伤等副作用。5% YQ23的有益效果等同于相同体积的WB + LR。HBOC如YQ23在损伤控制复苏的急救中发挥了重要作用，通过增加氧输送、减少器官损伤使院前治疗中的失血性休克受益。此外，HBOC可通过延长黄金时间使受伤和创伤患者受益。
