Fresh frozen plasma-based resuscitation lessens lung injury in mice with abdominal sepsis and hemorrhagic shock

Abstract We have previously shown that fresh frozen plasma (FFP) and fibrinogen have protective effects in mice with hemorrhagic shock through restoration of endothelial syndecan-1 and reversal of endothelial injury. In the current study, we tested the hypothesis that a combined model of abdominal sepsis and hemorrhagic shock would induce endothelial syndecan-1 shedding and lung injury which could be attenuated by both FFP and fibrinogen. C57BL/6 mice underwent cecal ligation and puncture (CLP) followed by hemorrhagic shock (HS) and fluid resuscitation with lactated Ringer’s (LR), fibrinogen (5 mg/mouse), and FFP, all at 1X shed blood volume. After 24 h, lung tissues and plasma were harvested for assays. CLP + HS induced an increase in alveolar thickness and decreases in lung syndecan-1 and lung neutrophil granule-enzymes (myeloperoxidase, neutrophil elastase, and MMP9), with reciprocal elevations in plasma syndecan-1 and plasma neutrophil granule-enzymes (myeloperoxidase, neutrophil elastase, and MMP9). All these alterations were significantly attenuated by FFP but not by fibrinogen. Additionally, CLP + HS-induced hypotension at 24 h was partially reversed by FFP but not by fibrinogen. Our results suggest that FFP administration was associated with inhibition of CLP + HS-induced neutrophil degranulation to prevent syndecan-1 shedding and lung injury. The present results provide preclinical evidence supporting further investigation of FFP for therapeutic use in traumatic hemorrhagic shock with sepsis.