Resuscitation from Hemorrhagic Shock with a Novel Protein Cocktail Restores Microvascular Perfusion and Protects Vital Organs

利用新型蛋白质混合物复苏出血性休克可恢复微血管灌注并保护重要器官

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Abstract

INTRODUCTION: Low-titer O positive whole blood (LTOWB) has been introduced in prehospital care to resuscitate patients; however, the logistical obstacles, cost of carrying LTOWB, and the availability of it in trauma situations are a point of concern. Therefore, fluids, like lactated Ringer's (LR) and hydroxyethyl starch (HES), have been considered alternatives to LTOWB transfusion. Unfortunately, they dilute plasma proteins in the circulation and have unfavorable side effects. This study presents an alternative, a protein cocktail (PC). The PC combines human serum albumin, transferrin, haptoglobin, and hemopexin. This study compares the ability to resuscitate from hemorrhagic shock (HS) with whole blood (WB), LR, 6% HES, and PC. METHODS: Unanesthetized golden Syrian hamsters instrumented with the dorsal window chambers were subjected to hemorrhage (50% blood volume), followed by 30 min hypovolemic shock, and resuscitated with 50% shed volume. The outcome was evaluated through systemic parameters, blood gases, microcirculatory hemodynamics, oxygen tension and saturation, metabolomics, and markers of organ injury/function. Additionally, to investigate the impact of the experimental solutions on the coagulation cascade, Sprague-Dawley rats were subjected to an isovolemic exchange infusion of 20% of the animal's blood volume. RESULTS: The PC showed favorable outcomes, restoring microvasculature hemodynamics comparable to resuscitation with WB and superior to LR and HES. PC reduced acute inflammation, positively impacted organ function markers, and restored metabolomic homeostasis without coagulopathies observed with HES. CONCLUSION: In conclusion, the PC shows some promise as a resuscitation from HS when WB is not available and superior to classic crystalloids and colloids (LR and HES). Further studies with the PC are needed to ensure its efficacy and safety in other experimental models.

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